The axon guidance molecule semaphorin 3F is a negative regulator of tumor progression and proliferation in ileal neuroendocrine tumors

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Vercherat, Cécile; Blanc, Martine; Lepinasse, Florian; Gadot, Nicolas; Couderc, Christophe; Poncet, Gilles; Walter, Thomas; Joly, Marie-Odile; Hervieu, Valérie; Scoazec, Jean-Yves; Roche, Colette

2015-01-01

Gastro-intestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, frequently metastatic, raising difficult clinical and therapeutic challenges due to a poor knowledge of their biology. As neuroendocrine cells express both epithelial and neural cell markers, we studied the possible involvement in GI-NETs of axon guidance molecules, which have been shown to decrease tumor cell proliferation and metastatic dissemination in several tumor types. We focused on the role of Semaphorin 3F (SEMA3F) in ileal NETs, one of the most frequent subtypes of GI-NETs. SEMA3F expression was detected in normal neuroendocrine cells but was lost in most of human primary tumors and all their metastases. SEMA3F loss of expression was associated with promoter gene methylation. After increasing endogenous SEMA3F levels through stable transfection, enteroendocrine cell lines STC-1 and GluTag showed a reduced proliferation rate in vitro. In two different xenograft mouse models, SEMA3F-overexpressing cells exhibited a reduced ability to form tumors and a hampered liver dissemination potential in vivo. This resulted, at least in part, from the inhibition of mTOR and MAPK signaling pathways. This study demonstrates an anti-tumoral role of SEMA3F in ileal NETs. We thus suggest that SEMA3F and/or its cellular signaling pathway could represent a target for ileal NET therapy. PMID:26447612

The self-consistent effective medium approximation (SEMA): New tricks from an old dog

International Nuclear Information System (INIS)

Bergman, David J.

2007-01-01

The fact that the self-consistent effective medium approximation (SEMA) leads to incorrect values for the percolation threshold, as well as for the critical exponents which characterize that threshold, has led to a decline in using that approximation. In this article I argue that SEMA has the unique capability, which is lacking in other approximation schemes for macroscopic response of composite media, of leading to the discovery or prediction of new critical points. This is due to the fact that SEMA can often lead to explicit equations for the macroscopic response of a composite medium, even when that medium has a rather complicated character. In such cases, the SEMA equations are usually coupled and nonlinear, often even transcendental in character. Thus there is no question of finding exact solutions. Nevertheless, a useful ansatz, leading to a closed form asymptotic solution, can often be made. In this way, singularities in the macroscopic response can be identified from a theoretical or mathematical treatment of the physical problem. This is demonstrated for two problems of magneto-transport in a composite medium, where the SEMA equations are solved using asymptotic analysis, leading to new types of critical points and critical behavior

Differential endothelial transcriptomics identifies semaphorin 3G as a vascular class 3 semaphorin.

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Kutschera, Simone; Weber, Holger; Weick, Anja; De Smet, Frederik; Genove, Guillem; Takemoto, Minoru; Prahst, Claudia; Riedel, Maria; Mikelis, Constantinos; Baulande, Sylvain; Champseix, Catherine; Kummerer, Petra; Conseiller, Emmanuel; Multon, Marie-Christine; Heroult, Melanie; Bicknell, Roy; Carmeliet, Peter; Betsholtz, Christer; Augustin, Hellmut G

2011-01-01

To characterize the role of a vascular-expressed class 3 semaphorin (semaphorin 3G [Sema3G]). Semaphorins have been identified as axon guidance molecules. Yet, they have more recently also been characterized as attractive and repulsive regulators of angiogenesis. Through a transcriptomic screen, we identified Sema3G as a molecule of angiogenic endothelial cells. Sema3G-deficient mice are viable and exhibit no overt vascular phenotype. Yet, LacZ expression in the Sema3G locus revealed intense arterial vascular staining in the angiogenic vasculature, starting at E9.5, which was detectable throughout adolescence and downregulated in adult vasculature. Sema3G is expressed as a full-length 100-kDa secreted molecule that is processed by furin proteases to yield 95- and a 65-kDa Sema domain-containing subunits. Full-length Sema3G binds to NP2, whereas processed Sema3G binds to NP1 and NP2. Expression profiling and cellular experiments identified autocrine effects of Sema3G on endothelial cells and paracrine effects on smooth muscle cells. Although the mouse knockout phenotype suggests compensatory mechanisms, the experiments identify Sema3G as a primarily endothelial cell-expressed class 3 semaphorin that controls endothelial and smooth muscle cell functions in autocrine and paracrine manners, respectively.

mTOR Complex Signaling through the SEMA4A-Plexin B2 Axis Is Required for Optimal Activation and Differentiation of CD8+ T Cells.

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Ito, Daisuke; Nojima, Satoshi; Nishide, Masayuki; Okuno, Tatsusada; Takamatsu, Hyota; Kang, Sujin; Kimura, Tetsuya; Yoshida, Yuji; Morimoto, Keiko; Maeda, Yohei; Hosokawa, Takashi; Toyofuku, Toshihiko; Ohshima, Jun; Kamimura, Daisuke; Yamamoto, Masahiro; Murakami, Masaaki; Morii, Eiichi; Rakugi, Hiromi; Isaka, Yoshitaka; Kumanogoh, Atsushi

2015-08-01

Mammalian target of rapamycin (mTOR) plays crucial roles in activation and differentiation of diverse types of immune cells. Although several lines of evidence have demonstrated the importance of mTOR-mediated signals in CD4(+) T cell responses, the involvement of mTOR in CD8(+) T cell responses is not fully understood. In this study, we show that a class IV semaphorin, SEMA4A, regulates CD8(+) T cell activation and differentiation through activation of mTOR complex (mTORC) 1. SEMA4A(-/-) CD8(+) T cells exhibited impairments in production of IFN-γ and TNF-α and induction of the effector molecules granzyme B, perforin, and FAS-L. Upon infection with OVA-expressing Listeria monocytogenes, pathogen-specific effector CD8(+) T cell responses were significantly impaired in SEMA4A(-/-) mice. Furthermore, SEMA4A(-/-) CD8(+) T cells exhibited reduced mTORC1 activity and elevated mTORC2 activity, suggesting that SEMA4A is required for optimal activation of mTORC1 in CD8(+) T cells. IFN-γ production and mTORC1 activity in SEMA4A(-/-) CD8(+) T cells were restored by administration of recombinant Sema4A protein. In addition, we show that plexin B2 is a functional receptor of SEMA4A in CD8(+) T cells. Collectively, these results not only demonstrate the role of SEMA4A in CD8(+) T cells, but also reveal a novel link between a semaphorin and mTOR signaling. Copyright © 2015 by The American Association of Immunologists, Inc.

Inactivation of the Sema5a gene results in embryonic lethality and defective remodeling of the cranial vascular system

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Fiore, Roberto; Rahim, Belquis; Christoffels, Vincent M.; Moorman, Antoon F. M.; Püschel, Andreas W.

2005-01-01

The semaphorins are a large family of proteins involved in the patterning of both the vascular and the nervous systems. In order to analyze the function of the membrane-bound semaphorin 5A (Sema5A), we generated mice homozygous for a null mutation in the Sema5a gene. Homozygous null mutants die

The SEMA5A gene is associated with hippocampal volume, and their interaction is associated with performance on Raven's Progressive Matrices.

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Zhu, Bi; Chen, Chuansheng; Xue, Gui; Moyzis, Robert K; Dong, Qi; Chen, Chunhui; Li, Jin; He, Qinghua; Lei, Xuemei; Wang, Yunxin; Lin, Chongde

2014-03-01

The Allen Brain Atlas shows that the semaphorin 5A (SEMA5A) gene, which encodes an important protein for neurogenesis and neuronal apoptosis, is predominantly expressed in the human hippocampus. Structural and functional neuroimaging studies have further shown that the hippocampus plays an important role in the performance on Raven's Progressive Matrices (RPM), a measure of reasoning ability and general fluid intelligence. Thus far, however, no study has examined the relationships between the SEMA5A gene polymorphism, hippocampal volume, and RPM performance. The current study collected both structural MRI, genetic, and behavioral data in 329 healthy Chinese adults, and examined associations between SEMA5A variants, hippocampal volume, and performance on RAPM (the advanced form of RPM). After controlling for intracranial volume (ICV), sex, and age, SEMA5A genetic polymorphism at the SNP rs42352 had the strongest association with hippocampal volume (p=0.00000552 and 0.000103 for right and left hippocampal volumes, respectively), with TT homozygotes having higher hippocampal volume than the other genotypes. Furthermore, there was a high correlation between right hippocampal volume and RAPM performance (r=0.42, p=0.0000509) for SEMA5A rs42352 TT homozygotes. This study provides the first evidence for the involvement of the SEMA5A gene in hippocampal structure and their interaction on RAPM performance. Future studies of the hippocampus-RPM associations should consider genetic factors as potential moderators. Copyright © 2013 Elsevier Inc. All rights reserved.

A systematic expression analysis implicates Plexin-B2 and its ligand Sema4C in the regulation of the vascular and endocrine system.

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Zielonka, Matthias; Xia, Jingjing; Friedel, Roland H; Offermanns, Stefan; Worzfeld, Thomas

2010-09-10

Plexins serve as receptors for semaphorins and play important roles in the developing nervous system. Plexin-B2 controls decisive developmental programs in the neural tube and cerebellum. However, whether Plexin-B2 also regulates biological functions in adult nonneuronal tissues is unknown. Here we show by two methodologically independent approaches that Plexin-B2 is expressed in discrete cell types of several nonneuronal tissues in the adult mouse. In the vasculature, Plexin-B2 is selectively expressed in functionally specialized endothelial cells. In endocrine organs, Plexin-B2 localizes to the pancreatic islets of Langerhans and to both cortex and medulla of the adrenal gland. Plexin-B2 expression is also detected in certain types of immune and epithelial cells. In addition, we report on a systematic comparison of the expression patterns of Plexin-B2 and its ligand Sema4C, which show complementarity or overlap in some but not all tissues. Furthermore, we demonstrate that Plexin-B2 and its family member Plexin-B1 display largely nonredundant expression patterns. This work establishes Plexin-B2 and Sema4C as potential regulators of the vascular and endocrine system and provides an anatomical basis to understand the biological functions of this ligand-receptor pair. Copyright 2010 Elsevier Inc. All rights reserved.

mTORC1 is a critical mediator of oncogenic Semaphorin3A signaling

Energy Technology Data Exchange (ETDEWEB)

Yamada, Daisuke; Kawahara, Kohichi; Maeda, Takehiko, E-mail: maeda@nupals.ac.jp

2016-08-05

Aberration of signaling pathways by genetic mutations or alterations in the surrounding tissue environments can result in tumor development or metastasis. However, signaling molecules responsible for these processes have not been completely elucidated. Here, we used mouse Lewis lung carcinoma cells (LLC) to explore the mechanism by which the oncogenic activity of Semaphorin3A (Sema3A) signaling is regulated. Sema3A knockdown by shRNA did not affect apoptosis, but decreased cell proliferation in LLCs; both the mammalian target of rapamycin complex 1 (mTORC1) level and glycolytic activity were also decreased. In addition, Sema3A knockdown sensitized cells to inhibition of oxidative phosphorylation by oligomycin, but conferred resistance to decreased cell viability induced by glucose starvation. Furthermore, recombinant SEMA3A rescued the attenuation of cell proliferation and glycolytic activity in LLCs after Sema3A knockdown, whereas mTORC1 inhibition by rapamycin completely counteracted this effect. These results demonstrate that Sema3A signaling exerts its oncogenic effect by promoting an mTORC1-mediated metabolic shift from oxidative phosphorylation to aerobic glycolysis. -- Highlights: •Sema3A knockdown decreased proliferation of Lewis lung carcinoma cells (LLCs). •Sema3A knockdown decreased mTORC1 levels and glycolytic activity in LLCs. •Sema3A knockdown sensitized cells to inhibition of oxidative phosphorylation. •Sema3A promotes shift from oxidative phosphorylation to aerobic glycolysis via mTORC1.

Prostate cancer cells induce osteoblastic differentiation via semaphorin 3A.

Science.gov (United States)

Liu, Fuzhou; Shen, Weiwei; Qiu, Hao; Hu, Xu; Zhang, Chao; Chu, Tongwei

2015-03-01

Prostate cancer metastasis to bone is the second most commonly diagnosed malignant disease among men worldwide. Such metastatic disease is characterized by the presence of osteoblastic bone lesions, and is associated with high rates of mortality. However, the various mechanisms involved in prostate cancer-induced osteoblastic differentiation have not been fully explored. Semaphorin 3A (Sema 3A) is a newly identified regulator of bone metabolism which stimulates differentiation of pre-osteoblastic cells under physiological conditions. We investigated in this study whether prostate cancer cells can mediate osteoblastic activity through Sema 3A. We cultured osteoprogenitor MC3T3-E1 cells in prostate cancer-conditioned medium, and analyzed levels of Sema 3A protein in diverse prostate cancer cell lines to identify cell lines in which Sema 3A production showed a positive correlation with osteo-stimulation. C4-2 cells were stably transfected with Sema 3A short hairpin RNA to further determine whether Sema 3A contributes to the ability of C4-2 cells to induce osteoblastic differentiation. Down-regulation of Sema 3A expression decreased indicators of C4-2 CM-induced osteoblastic differentiation, including alkaline phosphatase production and mineralization. Additionally, silencing or neutralizing Sema 3A in C4-2 cells resulted in diminished β-catenin expression in osteogenitor MC3T3-E1 cells. Our results suggest that prostate cancer-induced osteoblastic differentiation is at least partially mediated by Sema 3A, and may be regulated by the β-catenin signalling pathway. Sema 3A may represent a novel target for treatment of prostate cancer-induced osteoblastic lesions. © 2014 Wiley Periodicals, Inc.

Semaphorin3A, Neuropilin-1, and PlexinA1 are required for lymphatic valve formation.

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Bouvrée, Karine; Brunet, Isabelle; Del Toro, Raquel; Gordon, Emma; Prahst, Claudia; Cristofaro, Brunella; Mathivet, Thomas; Xu, Yunling; Soueid, Jihane; Fortuna, Vitor; Miura, Nayoki; Aigrot, Marie-Stéphane; Maden, Charlotte H; Ruhrberg, Christiana; Thomas, Jean Léon; Eichmann, Anne

2012-08-03

The lymphatic vasculature plays a major role in fluid homeostasis, absorption of dietary lipids, and immune surveillance. Fluid transport depends on the presence of intraluminal valves within lymphatic collectors. Defective formation of lymphatic valves leads to lymphedema, a progressive and debilitating condition for which curative treatments are currently unavailable. How lymphatic valve formation is regulated remains largely unknown. We investigated if the repulsive axon guidance molecule Semaphorin3A (Sema3A) plays a role in lymphatic valve formation. We show that Sema3A mRNA is expressed in lymphatic vessels and that Sema3A protein binds to lymphatic valves expressing the Neuropilin-1 (Nrp1) and PlexinA1 receptors. Using mouse knockout models, we show that Sema3A is selectively required for lymphatic valve formation, via interaction with Nrp1 and PlexinA1. Sema3a(-/-) mice exhibit defects in lymphatic valve formation, which are not due to abnormal lymphatic patterning or sprouting, and mice carrying a mutation in the Sema3A binding site of Nrp1, or deficient for Plxna1, develop lymphatic valve defects similar to those seen in Sema3a(-/-) mice. Our data demonstrate an essential direct function of Sema3A-Nrp1-PlexinA1 signaling in lymphatic valve formation.

The Role Of Semaphorin 3A In The Skeletal System.

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Tang, Peifu; Yin, Pengbin; Lv, Houchen; Zhang, Licheng; Zhang, Lihai

2015-01-01

Semaphorin 3A (Sema3A), characterized by a conserved N-terminal "Sema" domain, was originally described as an axon guidance molecule. Recent research indicates that it performs a critical function in the skeletal system. This review highlights recent advances in understanding of the role of Sema3A in the skeletal system as a regulator of bone metabolism and as a potential drug target for bone disease therapy. We summarize Sema3A functions in osteoblastogenesis and osteoclastogenesis, as well as in innervation, and we discuss its multifunctional role in various bone diseases such as osteoporosis and low back pain. Despite limited research in this field, our aim is to promote further understanding of the function of Sema3A in the skeletal system.

Semaphorin 3A controls allergic and inflammatory responses in experimental allergic conjunctivitis

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Junmi Tanaka

2015-02-01

Full Text Available AIM: To assess the efficacy of topical Semaphorin-3A (SEMA3A in the treatment of allergic conjunctivitis. METHODS: Experimental allergic conjunctivitis (EAC mice model induced by short ragweed pollen (SRW in 4-week-old of BALB/c mice, mice were evaluated using haematoxylin and eosin (H&E staining, immunofluorescence and light microscope photographs. Early phase took the samples in 24h after instillation and late phase took the samples between 4 to 14d after the start of treatment. The study use of topical SEMA3A (10 U, 100 U, 1000 U eye drops and subconjunctival injection of SEMA3A with same concentration. For comparison, five types of allergy eyedrops were quantified using clinical characteristics. RESULTS: Clinical score of composite ocular symptoms of the mice treated with SEMA3A were significantly decreased both in the immediate phase and the late phase compared to those treated with commercial ophthalmic formulations and non-treatment mice. SEMA3A treatment attenuates infiltration of eosinophils entering into conjunctiva in EAC mice. The score of eosinophil infiltration in the conjunctiva of SEMA3A 1000 U-treated group were significantly lower than low-concentration of SEMA3A treated groups and non-treated group. SEMA3A treatment also suppressed T-cell proliferation in vitro and decreased serum total IgE levels in EAC mice. Moreover, Treatment of SEMA3A suppressed Th2-related cytokines (IL-5, IL-13 and IL-4 and pro-inflammatory cytokines (IFN-γ, IL-17 and TNF-α release, but increased regulatory cytokine IL-10 concentration in the conjunctiva of EAC mice. CONCLUSIONS: SEMA3A as a biological agent, showed the beneficial activity in ocular allergic processes with the less damage to the intraocular tissue. It is expected that SEMA3A may be contributed in patients with a more severe spectrum of refractory ocular allergic diseases including allergic conjunctivitis in the near future.

Decreased Expression of Semaphorin3A/Neuropilin-1 Signaling Axis in Apical Periodontitis

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Ying Lin

2017-01-01

Full Text Available Apical periodontitis (AP is a chronic infection of endodontic origin accompanied with bone destruction around the apical region. Semaphorin3A (Sema3A and neuropilin-1 (Nrp1 are regarded as a pair of immune regulators in bone metabolism. In this study, we firstly investigated the expression pattern of Sema3A/Nrp1 in apical periodontitis and its correlation with bone destruction. Using rat animal model, we analysed the level of mandibular bone destruction and the expression of Sema3A/Nrp1 on days 0, 7, 14, 21, 28, and 35 after pulp exposure. In addition, clinical samples from apical periodontitis patients were obtained to analyse the expression of Sema3A/Nrp1. These results indicated that the bone destruction level expanded from days 7 to 35. The number of positive cells and level of mRNA expression of Sema3A/Nrp1 were significantly decreased from days 7 to 35, with a negative correlation with bone destruction. Moreover, expression of Sema3A/Nrp1 in the AP group was reduced compared to the control group of clinical samples. In conclusion, decreased expression of Sema3A/Nrp1 was observed in periapical lesions and is potentially involved in the bone resorption of the periapical area, suggesting that Sema3A/Nrp1 may contribute to the pathological development of apical periodontitis.

Autocrine Semaphorin3A signaling is essential for the maintenance of stem-like cells in lung cancer

International Nuclear Information System (INIS)

Yamada, Daisuke; Takahashi, Kensuke; Kawahara, Kohichi; Maeda, Takehiko

2016-01-01

Cancer stem-like cells (CSCs) exist in tumor tissues composed of heterogeneous cell population and are characterized by their self-renewal capacity and tumorigenicity. Many studies demonstrate that eradication of CSCs prevents development and recurrences of tumor; yet, molecules critical for the maintenance of CSCs have not been completely understood. We previously reported that Semaphorin3A (Sema3a) knockdown suppressed the tumorigenicity and proliferative capacity of Lewis lung carcinoma (LLC) cells. Therefore, we identified Sema3a as an essential factor for the establishment or maintenance of CSCs derived from LLC (LLC-stem cell). shRNA against Sema3a was introduced into LLC cells to establish a LLC-stem cell line and its effects on tumorigenesis, sphere formation, and mTORC1 activity were tested. Sema3a knockdown completely abolished tumorigenicity and the sphere-formation and self-renewal ability of LLC-stem cells. The Sema3a knockdown was also associated with decreased expression of mRNA for stem cell markers. The self-renewal ability abolished by Sema3a knockdown could not be recovered by exogenous addition of recombinant SEMA3A. In addition, the activity of mammalian target of rapamycin complex 1 (mTORC1) and the expression of its substrate p70S6K1 were also decreased. These results demonstrate that Sema3a is a potential therapeutic target in eradication of CSCs. - Highlights: • Sema3a enhances tumorigenic capacity of cancer stem-like cells. • Sema3a is essential for the maintenance of cancer stem-like cells. • Sema3a can be a therapeutic target to eradicate cancer stem-like cells.

Teaching Literacy Skills to French Minimally Verbal School-Aged Children with Autism Spectrum Disorders with the Serious Game SEMA-TIC: An Exploratory Study.

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Serret, Sylvie; Hun, Stéphanie; Thümmler, Susanne; Pierron, Prescillia; Santos, Andreia; Bourgeois, Jérémy; Askenazy, Florence

2017-01-01

Learning to read is very challenging for children with Autism Spectrum Disorders (ASD), but also very important, as it can give them access to new knowledge. This is even more challenging in minimally verbal children, who do not have the verbal abilities to learn through usual methods. To address the learning of literacy skills in French minimally verbal school-aged children with ASD, we designed the serious game SEMA-TIC, which relies on non-verbal cognitive skills and uses specific learning strategies adapted to the features of autistic individuals. This study investigated the usability of SEMA-TIC (in terms of adaptability, efficiency, and effectiveness) for the acquisition of literacy skills in French minimally verbal school-aged children with ASD. Twenty-five children with ASD and no functional language participated in the study. Children in the training group received the SEMA-TIC training over 23 weeks (on average), while no intervention was provided to children in the non-training group. Results indicated that SEMA-TIC presents a suitable usability, as all participants were able to play (adaptability), to complete the training (efficiency) and to acquire significant literacy skills (effectiveness). Indeed, the literacy skills in the training group significantly improved after the training, as measured by specific experimental tasks (alphabet knowledge, word reading, word-non-word discrimination, sentence reading and word segmentation; all p ≤ 0.001) compared to the non-training group. More importantly, 3 out of 12 children of the training group could be considered as word decoders at the end of the intervention, whereas no children of the non-training group became able to decode words efficiently. The present study thus brings preliminary evidence that French minimally verbal school-aged children with ASD are able to learn literacy skills through SEMA-TIC, a specific computerized intervention consisting in a serious game based on non-verbal cognitive

Teaching Literacy Skills to French Minimally Verbal School-Aged Children with Autism Spectrum Disorders with the Serious Game SEMA-TIC: An Exploratory Study

Science.gov (United States)

Serret, Sylvie; Hun, Stéphanie; Thümmler, Susanne; Pierron, Prescillia; Santos, Andreia; Bourgeois, Jérémy; Askenazy, Florence

2017-01-01

Learning to read is very challenging for children with Autism Spectrum Disorders (ASD), but also very important, as it can give them access to new knowledge. This is even more challenging in minimally verbal children, who do not have the verbal abilities to learn through usual methods. To address the learning of literacy skills in French minimally verbal school-aged children with ASD, we designed the serious game SEMA-TIC, which relies on non-verbal cognitive skills and uses specific learning strategies adapted to the features of autistic individuals. This study investigated the usability of SEMA-TIC (in terms of adaptability, efficiency, and effectiveness) for the acquisition of literacy skills in French minimally verbal school-aged children with ASD. Twenty-five children with ASD and no functional language participated in the study. Children in the training group received the SEMA-TIC training over 23 weeks (on average), while no intervention was provided to children in the non-training group. Results indicated that SEMA-TIC presents a suitable usability, as all participants were able to play (adaptability), to complete the training (efficiency) and to acquire significant literacy skills (effectiveness). Indeed, the literacy skills in the training group significantly improved after the training, as measured by specific experimental tasks (alphabet knowledge, word reading, word-non-word discrimination, sentence reading and word segmentation; all p ≤ 0.001) compared to the non-training group. More importantly, 3 out of 12 children of the training group could be considered as word decoders at the end of the intervention, whereas no children of the non-training group became able to decode words efficiently. The present study thus brings preliminary evidence that French minimally verbal school-aged children with ASD are able to learn literacy skills through SEMA-TIC, a specific computerized intervention consisting in a serious game based on non-verbal cognitive

Teaching Literacy Skills to French Minimally Verbal School-Aged Children with Autism Spectrum Disorders with the Serious Game SEMA-TIC: An Exploratory Study

Directory of Open Access Journals (Sweden)

Sylvie Serret

2017-09-01

Full Text Available Learning to read is very challenging for children with Autism Spectrum Disorders (ASD, but also very important, as it can give them access to new knowledge. This is even more challenging in minimally verbal children, who do not have the verbal abilities to learn through usual methods. To address the learning of literacy skills in French minimally verbal school-aged children with ASD, we designed the serious game SEMA-TIC, which relies on non-verbal cognitive skills and uses specific learning strategies adapted to the features of autistic individuals. This study investigated the usability of SEMA-TIC (in terms of adaptability, efficiency, and effectiveness for the acquisition of literacy skills in French minimally verbal school-aged children with ASD. Twenty-five children with ASD and no functional language participated in the study. Children in the training group received the SEMA-TIC training over 23 weeks (on average, while no intervention was provided to children in the non-training group. Results indicated that SEMA-TIC presents a suitable usability, as all participants were able to play (adaptability, to complete the training (efficiency and to acquire significant literacy skills (effectiveness. Indeed, the literacy skills in the training group significantly improved after the training, as measured by specific experimental tasks (alphabet knowledge, word reading, word-non-word discrimination, sentence reading and word segmentation; all p ≤ 0.001 compared to the non-training group. More importantly, 3 out of 12 children of the training group could be considered as word decoders at the end of the intervention, whereas no children of the non-training group became able to decode words efficiently. The present study thus brings preliminary evidence that French minimally verbal school-aged children with ASD are able to learn literacy skills through SEMA-TIC, a specific computerized intervention consisting in a serious game based on non

A novel podocyte gene, semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation.

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Ishibashi, Ryoichi; Takemoto, Minoru; Akimoto, Yoshihiro; Ishikawa, Takahiro; He, Peng; Maezawa, Yoshiro; Sakamoto, Kenichi; Tsurutani, Yuya; Ide, Shintaro; Ide, Kana; Kawamura, Harukiyo; Kobayashi, Kazuki; Tokuyama, Hirotake; Tryggvason, Karl; Betsholtz, Christer; Yokote, Koutaro

2016-05-16

Kidney diseases including diabetic nephropathy have become huge medical problems, although its precise mechanisms are still far from understood. In order to increase our knowledge about the patho-physiology of kidney, we have previously identified >300 kidney glomerulus-enriched transcripts through large-scale sequencing and microarray profiling of the mouse glomerular transcriptome. One of the glomerulus-specific transcripts identified was semaphorin 3G (Sema3G) which belongs to the semaphorin family. The aim of this study was to analyze both the in vivo and in vitro functions of Sema3G in the kidney. Sema3G was expressed in glomerular podocytes. Although Sema3G knockout mice did not show obvious glomerular defects, ultrastructural analyses revealed partially aberrant podocyte foot processes structures. When these mice were injected with lipopolysaccharide to induce acute inflammation or streptozotocin to induce diabetes, the lack of Sema3G resulted in increased albuminuria. The lack of Sema3G in podocytes also enhanced the expression of inflammatory cytokines including chemokine ligand 2 and interleukin 6. On the other hand, the presence of Sema3G attenuated their expression through the inhibition of lipopolysaccharide-induced Toll like receptor 4 signaling. Taken together, our results surmise that the Sema3G protein is secreted by podocytes and protects podocytes from inflammatory kidney diseases and diabetic nephropathy.

Brain Endothelial Cells Control Fertility through Ovarian-Steroid–Dependent Release of Semaphorin 3A

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Messina, Andrea; Casoni, Filippo; Vanacker, Charlotte; Langlet, Fanny; Hobo, Barbara; Cagnoni, Gabriella; Gallet, Sarah; Hanchate, Naresh Kumar; Mazur, Danièle; Taniguchi, Masahiko; Mazzone, Massimiliano; Verhaagen, Joost; Ciofi, Philippe; Bouret, Sébastien G.; Tamagnone, Luca; Prevot, Vincent

2014-01-01

Neuropilin-1 (Nrp1) guides the development of the nervous and vascular systems, but its role in the mature brain remains to be explored. Here we report that the expression of the 65 kDa isoform of Sema3A, the ligand of Nrp1, by adult vascular endothelial cells, is regulated during the ovarian cycle and promotes axonal sprouting in hypothalamic neurons secreting gonadotropin-releasing hormone (GnRH), the neuropeptide controlling reproduction. Both the inhibition of Sema3A/Nrp1 signaling and the conditional deletion of Nrp1 in GnRH neurons counteract Sema3A-induced axonal sprouting. Furthermore, the localized intracerebral infusion of Nrp1- or Sema3A-neutralizing antibodies in vivo disrupts the ovarian cycle. Finally, the selective neutralization of endothelial-cell Sema3A signaling in adult Sema3a loxP/loxP mice by the intravenous injection of the recombinant TAT-Cre protein alters the amplitude of the preovulatory luteinizing hormone surge, likely by perturbing GnRH release into the hypothalamo-hypophyseal portal system. Our results identify a previously unknown function for 65 kDa Sema3A-Nrp1 signaling in the induction of axonal growth, and raise the possibility that endothelial cells actively participate in synaptic plasticity in specific functional domains of the adult central nervous system, thus controlling key physiological functions such as reproduction. PMID:24618750

Brain endothelial cells control fertility through ovarian-steroid-dependent release of semaphorin 3A.

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Giacobini, Paolo; Parkash, Jyoti; Campagne, Céline; Messina, Andrea; Casoni, Filippo; Vanacker, Charlotte; Langlet, Fanny; Hobo, Barbara; Cagnoni, Gabriella; Gallet, Sarah; Hanchate, Naresh Kumar; Mazur, Danièle; Taniguchi, Masahiko; Mazzone, Massimiliano; Verhaagen, Joost; Ciofi, Philippe; Bouret, Sébastien G; Tamagnone, Luca; Prevot, Vincent

2014-03-01

Neuropilin-1 (Nrp1) guides the development of the nervous and vascular systems, but its role in the mature brain remains to be explored. Here we report that the expression of the 65 kDa isoform of Sema3A, the ligand of Nrp1, by adult vascular endothelial cells, is regulated during the ovarian cycle and promotes axonal sprouting in hypothalamic neurons secreting gonadotropin-releasing hormone (GnRH), the neuropeptide controlling reproduction. Both the inhibition of Sema3A/Nrp1 signaling and the conditional deletion of Nrp1 in GnRH neurons counteract Sema3A-induced axonal sprouting. Furthermore, the localized intracerebral infusion of Nrp1- or Sema3A-neutralizing antibodies in vivo disrupts the ovarian cycle. Finally, the selective neutralization of endothelial-cell Sema3A signaling in adult Sema3aloxP/loxP mice by the intravenous injection of the recombinant TAT-Cre protein alters the amplitude of the preovulatory luteinizing hormone surge, likely by perturbing GnRH release into the hypothalamo-hypophyseal portal system. Our results identify a previously unknown function for 65 kDa Sema3A-Nrp1 signaling in the induction of axonal growth, and raise the possibility that endothelial cells actively participate in synaptic plasticity in specific functional domains of the adult central nervous system, thus controlling key physiological functions such as reproduction.

Brain endothelial cells control fertility through ovarian-steroid-dependent release of semaphorin 3A.

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Paolo Giacobini

2014-03-01

Full Text Available Neuropilin-1 (Nrp1 guides the development of the nervous and vascular systems, but its role in the mature brain remains to be explored. Here we report that the expression of the 65 kDa isoform of Sema3A, the ligand of Nrp1, by adult vascular endothelial cells, is regulated during the ovarian cycle and promotes axonal sprouting in hypothalamic neurons secreting gonadotropin-releasing hormone (GnRH, the neuropeptide controlling reproduction. Both the inhibition of Sema3A/Nrp1 signaling and the conditional deletion of Nrp1 in GnRH neurons counteract Sema3A-induced axonal sprouting. Furthermore, the localized intracerebral infusion of Nrp1- or Sema3A-neutralizing antibodies in vivo disrupts the ovarian cycle. Finally, the selective neutralization of endothelial-cell Sema3A signaling in adult Sema3aloxP/loxP mice by the intravenous injection of the recombinant TAT-Cre protein alters the amplitude of the preovulatory luteinizing hormone surge, likely by perturbing GnRH release into the hypothalamo-hypophyseal portal system. Our results identify a previously unknown function for 65 kDa Sema3A-Nrp1 signaling in the induction of axonal growth, and raise the possibility that endothelial cells actively participate in synaptic plasticity in specific functional domains of the adult central nervous system, thus controlling key physiological functions such as reproduction.

Semaphorin 3A Induces Odontoblastic Phenotype in Dental Pulp Stem Cells.

Science.gov (United States)

Yoshida, S; Wada, N; Hasegawa, D; Miyaji, H; Mitarai, H; Tomokiyo, A; Hamano, S; Maeda, H

2016-10-01

In cases of pulp exposure due to deep dental caries or severe traumatic injuries, existing pulp-capping materials have a limited ability to reconstruct dentin-pulp complexes and can result in pulpectomy because of their low potentials to accelerate dental pulp cell activities, such as migration, proliferation, and differentiation. Therefore, the development of more effective therapeutic agents has been anticipated for direct pulp capping. Dental pulp tissues are enriched with dental pulp stem cells (DPSCs). Here, the authors investigated the effects of semaphorin 3A (Sema3A) on various functions of human DPSCs in vitro and reparative dentin formation in vivo in a rat dental pulp exposure model. Immunofluorescence staining revealed expression of Sema3A and its receptor Nrp1 (neuropilin 1) in rat dental pulp tissue and human DPSC clones. Sema3A induced cell migration, chemotaxis, proliferation, and odontoblastic differentiation of DPSC clones. In addition, Sema3A treatment of DPSC clones increased β-catenin nuclear accumulation, upregulated expression of the FARP2 gene (FERM, RhoGEF, and pleckstrin domain protein 2), and activated Rac1 in DPSC clones. Furthermore, in the rat dental pulp exposure model, Sema3A promoted reparative dentin formation with dentin tubules and a well-aligned odontoblast-like cell layer at the dental pulp exposure site and with novel reparative dentin almost completely covering pulp tissue at 4 wk after direct pulp capping. These findings suggest that Sema3A could play an important role in dentin regeneration via canonical Wnt/β-catenin signaling. Sema3A might be an alternative agent for direct pulp capping, which requires further study. © International & American Associations for Dental Research 2016.

Vonis Mati Bandar Dan Pengedar Narkoba Antara Putusan Mk Dan Sema (Perspektif Hukum Pidana Islam)

OpenAIRE

Irfan, M Nurul

2014-01-01

: The Dead Penalty for the Drug Dealers in the Constitutional Court and the Sema (an Islamic Criminal Law Perspective). The death sentence set by the Supreme Court for the agents and drug dealers has attracted attention of criminal law experts. Constitutional Court Decision No. 34 / PUU-X /2013 which annuls Article 268 paragraph (3) Criminal Procedure Code-stating that the submission PK (judicial review) can only be done once- has open a chance that the PK can be submitted more than once. Thi...

Infantile hemangioma-derived stem cells and endothelial cells are inhibited by class 3 semaphorins

International Nuclear Information System (INIS)

Nakayama, Hironao; Huang, Lan; Kelly, Ryan P.; Oudenaarden, Clara R.L.; Dagher, Adelle; Hofmann, Nicole A.; Moses, Marsha A.; Bischoff, Joyce; Klagsbrun, Michael

2015-01-01

Class 3 semaphorins were discovered as a family of axon guidance molecules, but are now known to be involved in diverse biologic processes. In this study, we investigated the anti-angiogenic potential of SEMA3E and SEMA3F (SEMA3E&F) in infantile hemangioma (IH). IH is a common vascular tumor that involves both vasculogenesis and angiogenesis. Our lab has identified and isolated hemangioma stem cells (HemSC), glucose transporter 1 positive (GLUT1 + ) endothelial cells (designated as GLUT1 sel cells) based on anti-GLUT1 magnetic beads selection and GLUT1-negative endothelial cells (named HemEC). We have shown that these types of cells play important roles in hemangiogenesis. We report here that SEMA3E inhibited HemEC migration and proliferation while SEMA3F was able to suppress the migration and proliferation in all three types of cells. Confocal microscopy showed that stress fibers in HemEC were reduced by SEMA3E&F and that stress fibers in HemSC were decreased by SEMA3F, which led to cytoskeletal collapse and loss of cell motility in both cell types. Additionally, SEMA3E&F were able to inhibit vascular endothelial growth factor (VEGF)-induced sprouts in all three types of cells. Further, SEMA3E&F reduced the level of p-VEGFR2 and its downstream p-ERK in HemEC. These results demonstrate that SEMA3E&F inhibit IH cell proliferation and suppress the angiogenic activities of migration and sprout formation. SEMA3E&F may have therapeutic potential to treat or prevent growth of highly proliferative IH. - Highlights: • SEMA3E&F reduce actin stress fibers and induce cytoskeletal collapse in HemEC. • SEMA3E&F inhibit angiogenic activities of HemEC. • SEMA3E&F can interrupt the VEGF-A-VEGFR2-ERK signaling pathway in HemEC. • Plexin D1 and NRP2 are induced during HemSC/GLUT1 sel -to-EC differentiation

Infantile hemangioma-derived stem cells and endothelial cells are inhibited by class 3 semaphorins

Energy Technology Data Exchange (ETDEWEB)

Nakayama, Hironao [Vascular Biology Program, Boston Children' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Department of Surgery, Boston Children' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Division of Cell Growth and Tumor Regulation, Proteo-Science Center, Ehime University, Toon, Ehime 791-0295 (Japan); Huang, Lan [Vascular Biology Program, Boston Children' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Department of Surgery, Boston Children' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Kelly, Ryan P.; Oudenaarden, Clara R.L. [Vascular Biology Program, Boston Children' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Dagher, Adelle; Hofmann, Nicole A.; Moses, Marsha A. [Vascular Biology Program, Boston Children' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Department of Surgery, Boston Children' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Bischoff, Joyce, E-mail: joyce.bischoff@childrens.harvard.edu [Vascular Biology Program, Boston Children' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Department of Surgery, Boston Children' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Klagsbrun, Michael, E-mail: michael.klagsbrun@childrens.harvard.edu [Vascular Biology Program, Boston Children' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Department of Surgery, Boston Children' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Department of Pathology, Boston Children' s Hospital, Harvard Medical School, Boston, MA 02115 (United States)

2015-08-14

Class 3 semaphorins were discovered as a family of axon guidance molecules, but are now known to be involved in diverse biologic processes. In this study, we investigated the anti-angiogenic potential of SEMA3E and SEMA3F (SEMA3E&F) in infantile hemangioma (IH). IH is a common vascular tumor that involves both vasculogenesis and angiogenesis. Our lab has identified and isolated hemangioma stem cells (HemSC), glucose transporter 1 positive (GLUT1{sup +}) endothelial cells (designated as GLUT1{sup sel} cells) based on anti-GLUT1 magnetic beads selection and GLUT1-negative endothelial cells (named HemEC). We have shown that these types of cells play important roles in hemangiogenesis. We report here that SEMA3E inhibited HemEC migration and proliferation while SEMA3F was able to suppress the migration and proliferation in all three types of cells. Confocal microscopy showed that stress fibers in HemEC were reduced by SEMA3E&F and that stress fibers in HemSC were decreased by SEMA3F, which led to cytoskeletal collapse and loss of cell motility in both cell types. Additionally, SEMA3E&F were able to inhibit vascular endothelial growth factor (VEGF)-induced sprouts in all three types of cells. Further, SEMA3E&F reduced the level of p-VEGFR2 and its downstream p-ERK in HemEC. These results demonstrate that SEMA3E&F inhibit IH cell proliferation and suppress the angiogenic activities of migration and sprout formation. SEMA3E&F may have therapeutic potential to treat or prevent growth of highly proliferative IH. - Highlights: • SEMA3E&F reduce actin stress fibers and induce cytoskeletal collapse in HemEC. • SEMA3E&F inhibit angiogenic activities of HemEC. • SEMA3E&F can interrupt the VEGF-A-VEGFR2-ERK signaling pathway in HemEC. • Plexin D1 and NRP2 are induced during HemSC/GLUT1{sup sel}-to-EC differentiation.

The axonal guidance cue semaphorin 3C contributes to alveolar growth and repair.

Directory of Open Access Journals (Sweden)

Arul Vadivel

Full Text Available Lung diseases characterized by alveolar damage such as bronchopulmonary dysplasia (BPD in premature infants and emphysema lack efficient treatments. Understanding the mechanisms contributing to normal and impaired alveolar growth and repair may identify new therapeutic targets for these lung diseases. Axonal guidance cues are molecules that guide the outgrowth of axons. Amongst these axonal guidance cues, members of the Semaphorin family, in particular Semaphorin 3C (Sema3C, contribute to early lung branching morphogenesis. The role of Sema3C during alveolar growth and repair is unknown. We hypothesized that Sema3C promotes alveolar development and repair. In vivo Sema3C knock down using intranasal siRNA during the postnatal stage of alveolar development in rats caused significant air space enlargement reminiscent of BPD. Sema3C knock down was associated with increased TLR3 expression and lung inflammatory cells influx. In a model of O2-induced arrested alveolar growth in newborn rats mimicking BPD, air space enlargement was associated with decreased lung Sema3C mRNA expression. In vitro, Sema3C treatment preserved alveolar epithelial cell viability in hyperoxia and accelerated alveolar epithelial cell wound healing. Sema3C preserved lung microvascular endothelial cell vascular network formation in vitro under hyperoxic conditions. In vivo, Sema3C treatment of hyperoxic rats decreased lung neutrophil influx and preserved alveolar and lung vascular growth. Sema3C also preserved lung plexinA2 and Sema3C expression, alveolar epithelial cell proliferation and decreased lung apoptosis. In conclusion, the axonal guidance cue Sema3C promotes normal alveolar growth and may be worthwhile further investigating as a potential therapeutic target for lung repair.

Semaphorin7A and its receptors: pleiotropic regulators of immune cell function, bone homeostasis, and neural development.

Science.gov (United States)

Jongbloets, Bart C; Ramakers, Geert M J; Pasterkamp, R Jeroen

2013-03-01

Semaphorins form a large, evolutionary conserved family of cellular guidance signals. The semaphorin family contains several secreted and transmembrane proteins, but only one GPI-anchored member, Semaphorin7A (Sema7A). Although originally identified in immune cells, as CDw108, Sema7A displays widespread expression outside the immune system. It is therefore not surprising that accumulating evidence supports roles for this protein in a wide variety of biological processes in different organ systems and in disease. Well-characterized biological effects of Sema7A include those during bone and immune cell regulation, neuron migration and neurite growth. These effects are mediated by two receptors, plexinC1 and integrins. However, most of what is known today about Sema7A signaling concerns Sema7A-integrin interactions. Here, we review our current knowledge of Sema7A function and signaling in different organ systems, highlighting commonalities between the cellular effects and signaling pathways activated by Sema7A in different cell types. Furthermore, we discuss a potential role for Sema7A in disease and provide directions for further research. Copyright © 2013 Elsevier Ltd. All rights reserved.

A PKC-dependent recruitment of MMP-2 controls semaphorin-3A growth-promoting effect in cortical dendrites.

Directory of Open Access Journals (Sweden)

Bertrand Gonthier

Full Text Available There is increasing evidence for a crucial role of proteases and metalloproteinases during axon growth and guidance. In this context, we recently described a functional link between the chemoattractive Sema3C and Matrix metalloproteinase 3 (MMP3. Here, we provide data demonstrating the involvement of MMP-2 to trigger the growth-promoting effect of Sema3A in cortical dendrites. The in situ analysis of MMP-2 expression and activity is consistent with a functional growth assay demonstrating in vitro that the pharmacological inhibition of MMP-2 reduces the growth of cortical dendrites in response to Sema3A. Hence, our results suggest that the selective recruitment and activation of MMP-2 in response to Sema3A requires a PKC alpha dependent mechanism. Altogether, we provide a second set of data supporting MMPs as effectors of the growth-promoting effects of semaphorins, and we identify the potential signalling pathway involved.

Changes in expression of Class 3 Semaphorins and their receptors during development of the rat retina and superior colliculus.

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Sharma, Anil; LeVaillant, Chrisna J; Plant, Giles W; Harvey, Alan R

2014-07-26

Members of the Semaphorin 3 family (Sema3s) influence the development of the central nervous system, and some are implicated in regulating aspects of visual system development. However, we lack information about the timing of expression of the Sema3s with respect to different developmental epochs in the mammalian visual system. In this time-course study in the rat, we document for the first time changes in the expression of RNAs for the majority of Class 3 Semaphorins (Sema3s) and their receptor components during the development of the rat retina and superior colliculus (SC). During retinal development, transcript levels changed for all of the Sema3s examined, as well as Nrp2, Plxna2, Plxna3, and Plxna4a. In the SC there were also changes in transcript levels for all Sema3s tested, as well as Nrp1, Nrp2, Plxna1, Plxna2, Plxna3, and Plxna4a. These changes correlate with well-established epochs, and our data suggest that the Sema3s could influence retinal ganglion cell (RGC) apoptosis, patterning and connectivity in the maturing retina and SC, and perhaps guidance of RGC and cortical axons in the SC. Functionally we found that SEMA3A, SEMA3C, SEMA3E, and SEMA3F proteins collapsed purified postnatal day 1 RGC growth cones in vitro. Significantly this is a developmental stage when RGCs are growing into and within the SC and are exposed to Sema3 ligands. These new data describing the overall temporal regulation of Sema3 expression in the rat retina and SC provide a platform for further work characterising the functional impact of these proteins on the development and maturation of mammalian visual pathways.

Transcription of a novel mouse semaphorin gene, M-semaH, correlates with the metastatic ability of mouse tumor cell lines

DEFF Research Database (Denmark)

Christensen, C R; Klingelhöfer, Jörg; Tarabykina, S

1998-01-01

identified a novel member of the semaphorin/collapsin family in the two metastatic cell lines. We have named it M-semaH. Northern hybridization to a panel of tumor cell lines revealed transcripts in 12 of 12 metastatic cell lines but in only 2 of 6 nonmetastatic cells and none in immortalized mouse...

The association between semaphorin 3A levels and gluten-free diet in patients with celiac disease.

Science.gov (United States)

Kessel, Aharon; Lin, Chen; Vadasz, Zahava; Peri, Regina; Eiza, Nasren; Berkowitz, Drora

2017-11-01

Celiac disease (CD) is an inflammatory disease affecting the small intestine. We aim to assess serum level and expression of semaphorin 3A (Sema3A) on T regulatory (Treg) cells in CD patients. Twenty-six newly diagnosed celiac patients, 13 celiac patients on a gluten-free diet and 16 healthy controls included in the study. Sema3A protein level in the serum of celiac patients was significantly higher compared to healthy group (7.17±1.8ng/ml vs. 5.67±1.5ng/ml, p=0.012). Sema3A expression on Treg cells was statistically lower in celiac patients compared to healthy subjects (p=0.009) and significantly lower in celiac patients compared to celiac patients on gluten free diet (p=0.04). Negative correlation was found between Sema3A on Teg cells and the level of IgA anti-tTG antibodies (r=-0.346, p<0.01) and anti-DGP (r=-0.448, p<0.01). This study suggests involvement of the Sema3A in the pathogenesis of CD. Copyright © 2017 Elsevier Inc. All rights reserved.

Anti-proliferative effects of gold nanoparticles functionalized with Semaphorin 3F

Science.gov (United States)

Tan, Gamze; Onur, Mehmet Ali

2017-08-01

The new vessel formations play a vital role in growth and spread of cancer. Current anti-angiogenic therapies, predominantly based on vascular endothelial growth factor (VEGF) inhibition, can inhibit vascular development; however, they are usually ineffective against the primary tumor occurrence. The aim of this study was to assess anti-angiogenic effects of gold nanoparticles (AuNPs) functionalized with Semaphorin (Sema) 3F protein. The polyethylene glycol (PEG)-coated AuNPs were covalently functionalized with Sema 3F and labeled with the TAMRA fluorescent dye. The effect of the NPs on human umbilical vein endothelial cells (HUVECs) is probed in the way of internalization and viability assays. AuNP-Sema 3F bioconjugates showed great endothelial cell uptake. AuNP-Sema 3F bioconjugates reduced VEGF165-induced endothelial cell proliferation more effectively than Sema 3F alone, suggesting that the therapeutic effects of Sema 3F can be improved by conjugation to AuNPs. Also, no significant toxicity effect was induced by bioconjugates. This is the first study that reports a covalent binding of full length Sema 3F to NPs. The exogenously administration of Sema 3F, which has both anti-angiogenic and anti-tumoral activity, to tumor vasculature via a carrying platform may not only lead to more effective anti-angiogenic treatment but also may make current approach more applicable in clinical use like drug delivery system. [Figure not available: see fulltext.

Frequent deletion of 3p21.1 region carrying semaphorin 3G and aberrant expression of the genes participating in semaphorin signaling in the epithelioid type of malignant mesothelioma cells.

Science.gov (United States)

Yoshikawa, Yoshie; Sato, Ayuko; Tsujimura, Tohru; Morinaga, Tomonori; Fukuoka, Kazuya; Yamada, Shusai; Murakami, Aki; Kondo, Nobuyuki; Matsumoto, Seiji; Okumura, Yoshitomo; Tanaka, Fumihiro; Hasegawa, Seiki; Hashimoto-Tamaoki, Tomoko; Nakano, Takashi

2011-12-01

Array-based comparative genomic hybridization analysis was performed on 21 malignant mesothelioma (MM) samples (16 primary cell cultures and 5 cell lines) and two reactive mesothelial hyperplasia (RM) primary cell cultures. The RM samples did not have any genomic losses or gains. In MM samples, deletions in 1p, 3p21, 4q, 9p21, 16p13 and 22q were detected frequently. We focused on 3p21 because this deletion was specific to the epithelioid type. Especially, a deletion in 3p21.1 region carrying seven genes including SEMA3G was found in 52% of MM samples (11 of 14 epithelioid samples). The allele loss of 3p21.1 might be a good marker for the epithelioid MM. A homozygous deletion in this region was detected in two MM primary cell cultures. A heterozygous deletion detected in nine samples contained the 3p21.1 region and 3p21.31 one carrying the candidate tumor suppressor genes such as semaphorin 3F (SEMA3F), SEMA3B and Ras association (RalGDS/AF-6) domain family member 1 (RASSF1A). SEMA3B, 3F and 3G are class 3 semaphorins and inhibit growth by competing with vascular endothelial growth factor (VEGF) through binding to neuropilin. All MM samples downregulated the expression of more than one gene for SEMA3B, 3F and 3G when compared with Met5a, a normal pleura-derived cell line. Moreover, in 12 of 14 epithelioid MM samples the expression level of SEMA3A was lower than that in Met5a and the two RM samples. An augmented expression of VEGFA was detected in half of the MM samples. The expression ratio of VEGFA/SEMA3A was significantly higher in the epithelioid MMs than in Met5a, RMs and the non-epithelioid MMs. Our data suggest that the downregulated expression of SEMA3A and several SEMA3s results in a loss of inhibitory activities in tumor angiogenesis and tumor growth of VEGFA; therefore, it may play an important role on the pathogenesis of the epithelioid type of MM.

Urinary semaphorin 3A correlates with diabetic proteinuria and mediates diabetic nephropathy and associated inflammation in mice

NARCIS (Netherlands)

Mohamed, Riyaz; Ranganathan, Punithavathi; Jayakumar, Calpurnia; Nauta, Ferdau L.; Gansevoort, Ron T.; Weintraub, Neal L.; Brands, Michael; Ramesh, Ganesan

2014-01-01

Semaphorin 3A (sema3A) was recently identified as an early diagnostic biomarker of acute kidney injury. However, its role as a biomarker and/or mediator of chronic kidney disease (CKD) related to diabetic nephropathy is unknown. We examined the expression of sema3A in diabetic animal models and in

Varicose and cheerio collaborate with pebble to mediate semaphorin-1a reverse signaling in Drosophila.

Science.gov (United States)

Jeong, Sangyun; Yang, Da-Som; Hong, Young Gi; Mitchell, Sarah P; Brown, Matthew P; Kolodkin, Alex L

2017-09-26

The transmembrane semaphorin Sema-1a acts as both a ligand and a receptor to regulate axon-axon repulsion during neural development. Pebble (Pbl), a Rho guanine nucleotide exchange factor, mediates Sema-1a reverse signaling through association with the N-terminal region of the Sema-1a intracellular domain (ICD), resulting in cytoskeletal reorganization. Here, we uncover two additional Sema-1a interacting proteins, varicose (Vari) and cheerio (Cher), each with neuronal functions required for motor axon pathfinding. Vari is a member of the membrane-associated guanylate kinase (MAGUK) family of proteins, members of which can serve as scaffolds to organize signaling complexes. Cher is related to actin filament cross-linking proteins that regulate actin cytoskeleton dynamics. The PDZ domain binding motif found in the most C-terminal region of the Sema-1a ICD is necessary for interaction with Vari, but not Cher, indicative of distinct binding modalities. Pbl/Sema-1a-mediated repulsive guidance is potentiated by both vari and cher Genetic analyses further suggest that scaffolding functions of Vari and Cher play an important role in Pbl-mediated Sema-1a reverse signaling. These results define intracellular components critical for signal transduction from the Sema-1a receptor to the cytoskeleton and provide insight into mechanisms underlying semaphorin-induced localized changes in cytoskeletal organization.

Co-immobilization of semaphorin3A and nerve growth factor to guide and pattern axons.

Science.gov (United States)

McCormick, Aleesha M; Jarmusik, Natalie A; Leipzig, Nic D

2015-12-01

Immobilization of axon guidance cues offers a powerful tissue regenerative strategy to control the presentation and spatial location of these biomolecules. We use our previously developed immobilization strategy to specifically tether recombinant biotinylated nerve growth factor (bNGF) and biotinylated semaphorin3A (bSema3A) to chitosan films as an outgrowth and guidance platform. DRG neurite length and number for a range of single cues of immobilized bNGF or bSema3A were examined to determine a concentration response. Next single and dual cues of bNGF and bSema3A were immobilized and DRG guidance was assessed in response to a step concentration change from zero. Overall, immobilized groups caused axon extension, retraction and turning depending on the ratio of bNGF and bSema3A immobilized in the encountered region. This response indicated the exquisite sensitivity of DRG axons to both attractive and repulsive tethered cues. bSema3A concentrations of 0.10 and 0.49 ng/mm(2), when co-immobilized with bNGF (at 0.86 and 0.43 ng/mm(2) respectively), caused axons to turn away from the co-immobilized region. Immunocytochemical analysis showed that at these bSema3A concentrations, axons inside the co-immobilized region display microtubule degradation and breakdown of actin filaments. At the lowest bSema3A concentration (0.01 ng/mm(2)) co-immobilized with a higher bNGF concentration (2.16 ng/mm(2)), neurite lengths are shorter in the immobilized area, but bNGF dominates the guidance mechanism as neurites are directed toward the immobilized region. Future applications can pattern these cues in various geometries and gradients in order to better modulate axon guidance in terms of polarity, extension and branching. Nervous system formation and regeneration requires key molecules for guiding the growth cone and nervous system patterning. In vivo these molecules work in conjunction with one another to modulate axon guidance, and often they are tethered to limit spatial

Semaphorin 3G Provides a Repulsive Guidance Cue to Lymphatic Endothelial Cells via Neuropilin-2/PlexinD1.

Science.gov (United States)

Liu, Xinyi; Uemura, Akiyoshi; Fukushima, Yoko; Yoshida, Yutaka; Hirashima, Masanori

2016-11-22

The vertebrate circulatory system is composed of closely related blood and lymphatic vessels. It has been shown that lymphatic vascular patterning is regulated by blood vessels during development, but its molecular mechanisms have not been fully elucidated. Here, we show that the artery-derived ligand semaphorin 3G (Sema3G) and the endothelial cell receptor PlexinD1 play a role in lymphatic vascular patterning. In mouse embryonic back skin, genetic inactivation of Sema3G or PlexinD1 results in abnormal artery-lymph alignment and reduced lymphatic vascular branching. Conditional ablation in mice demonstrates that PlexinD1 is primarily required in lymphatic endothelial cells (LECs). In vitro analyses show that Sema3G binds to neuropilin-2 (Nrp2), which forms a receptor complex with PlexinD1. Sema3G induces cell collapse in an Nrp2/PlexinD1-dependent manner. Our findings shed light on a molecular mechanism by which LECs are distributed away from arteries and form a branching network during lymphatic vascular development. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Potential Role of Semaphorin 3A and Its Receptors in Regulating Aberrant Sympathetic Innervation in Peritoneal and Deep Infiltrating Endometriosis.

Science.gov (United States)

Liang, Yanchun; Wang, Wei; Huang, Jiaming; Tan, Hao; Liu, Tianyu; Shang, Chunliang; Liu, Duo; Guo, Luyan; Yao, Shuzhong

2015-01-01

Previous studies have demonstrated the involvement of nerve repellent factors in regulation of the imbalanced innervation of endometriosis. This prospective study aims to explore the role of Sema 3A in regulating aberrant sympathetic innervation in peritoneal and deep infiltrating endometriosis. Ectopic endometriotic lesion were collected from patients with peritoneal endometriosis (n = 24) and deep infiltrating endometriosis of uterosacral ligament (n = 20) undergoing surgery for endometriosis. Eutopic endometrial samples were collected from patients with endometriosis (n = 22) or without endometriosis (n = 26). Healthy peritoneum (n = 13) from the lateral pelvic wall and healthy uterosacral ligament (n = 13) were obtained from patients who had no surgical and histological proof of endometriosis during hysterectomy for uterine fibroids. Firstly, we studied the immunostaining of Sema 3A, Plexin A1 and NRP-1 in all the tissues described above. Then we studied the nerve fiber density (NFD) of endometriosis-associated (sympathetic) nerve and para-endometriotic (sympathetic) nerve by double immunofluorescence staining. Finally we analyzed the relationship between expression of Sema 3A in stromal cells of endometriotic lesion and the aberrant innervation of endometriosis. Semi-quantitative immunostaining demonstrated that (1) Higher immunostaining of Sema 3A were found in the eutopic endometrial glandular epithelial cells from patients with endometriosis (p = 0.041) than those without endometriosis; (2) Sema 3A immunostaining was higher in glandular epithelial cells of peritoneal endometriosis (Pendometriosis, while its expression in ectopic stormal cells in both groups were significantly lower than that from eutopic endometrium of women without endometirosis (Pendometriosis-associated sympathetic nerve of peritoneal endometriosis (pendometriosis of uterosacral ligament (pperitoneal and deep infiltrating endometriosis.

Potential Role of Semaphorin 3A and Its Receptors in Regulating Aberrant Sympathetic Innervation in Peritoneal and Deep Infiltrating Endometriosis

Science.gov (United States)

Liang, Yanchun; Wang, Wei; Huang, Jiaming; Tan, Hao; Liu, Tianyu; Shang, Chunliang; Liu, Duo; Guo, Luyan; Yao, Shuzhong

2015-01-01

Previous studies have demonstrated the involvement of nerve repellent factors in regulation of the imbalanced innervation of endometriosis. This prospective study aims to explore the role of Sema 3A in regulating aberrant sympathetic innervation in peritoneal and deep infiltrating endometriosis. Ectopic endometriotic lesion were collected from patients with peritoneal endometriosis (n = 24) and deep infiltrating endometriosis of uterosacral ligament (n = 20) undergoing surgery for endometriosis. Eutopic endometrial samples were collected from patients with endometriosis (n = 22) or without endometriosis (n = 26). Healthy peritoneum (n = 13) from the lateral pelvic wall and healthy uterosacral ligament (n = 13) were obtained from patients who had no surgical and histological proof of endometriosis during hysterectomy for uterine fibroids. Firstly, we studied the immunostaining of Sema 3A, Plexin A1 and NRP-1 in all the tissues described above. Then we studied the nerve fiber density (NFD) of endometriosis-associated (sympathetic) nerve and para-endometriotic (sympathetic) nerve by double immunofluorescence staining. Finally we analyzed the relationship between expression of Sema 3A in stromal cells of endometriotic lesion and the aberrant innervation of endometriosis. Semi-quantitative immunostaining demonstrated that (1) Higher immunostaining of Sema 3A were found in the eutopic endometrial glandular epithelial cells from patients with endometriosis (p = 0.041) than those without endometriosis; (2) Sema 3A immunostaining was higher in glandular epithelial cells of peritoneal endometriosis (Pendometriosis, while its expression in ectopic stormal cells in both groups were significantly lower than that from eutopic endometrium of women without endometirosis (Pendometriosis-associated sympathetic nerve of peritoneal endometriosis (pendometriosis of uterosacral ligament (pendometriosis. PMID:26720585

Semaphorin 3 C drives epithelial-to-mesenchymal transition, invasiveness, and stem-like characteristics in prostate cells.

Science.gov (United States)

Tam, Kevin J; Hui, Daniel H F; Lee, Wilson W; Dong, Mingshu; Tombe, Tabitha; Jiao, Ivy Z F; Khosravi, Shahram; Takeuchi, Ario; Peacock, James W; Ivanova, Larissa; Moskalev, Igor; Gleave, Martin E; Buttyan, Ralph; Cox, Michael E; Ong, Christopher J

2017-09-13

Prostate cancer (PCa) is among the most commonly-occurring cancers worldwide and a leader in cancer-related deaths. Local non-invasive PCa is highly treatable but limited treatment options exist for those with locally-advanced and metastatic forms of the disease underscoring the need to identify mechanisms mediating PCa progression. The semaphorins are a large grouping of membrane-associated or secreted signalling proteins whose normal roles reside in embryogenesis and neuronal development. In this context, semaphorins help establish chemotactic gradients and direct cell movement. Various semaphorin family members have been found to be up- and down-regulated in a number of cancers. One family member, Semaphorin 3 C (SEMA3C), has been implicated in prostate, breast, ovarian, gastric, lung, and pancreatic cancer as well as glioblastoma. Given SEMA3C's roles in development and its augmented expression in PCa, we hypothesized that SEMA3C promotes epithelial-to-mesenchymal transition (EMT) and stem-like phenotypes in prostate cells. In the present study we show that ectopic expression of SEMA3C in RWPE-1 promotes the upregulation of EMT and stem markers, heightened sphere-formation, and cell plasticity. In addition, we show that SEMA3C promotes migration and invasion in vitro and cell dissemination in vivo.

Chemoenzymatically prepared konjac ceramide inhibits NGF-induced neurite outgrowth by a semaphorin 3A-like action

Directory of Open Access Journals (Sweden)

Seigo Usuki

2016-03-01

Full Text Available Dietary sphingolipids such as glucosylceramide (GlcCer are potential nutritional factors associated with prevention of metabolic syndrome. Our current understanding is that dietary GlcCer is degraded to ceramide and further metabolized to sphingoid bases in the intestine. However, ceramide is only found in trace amounts in food plants and thus is frequently taken as GlcCer in a health supplement. In the present study, we successfully prepared konjac ceramide (kCer using endoglycoceramidase I (EGCase I. Konjac, a plant tuber, is an enriched source of GlcCer (kGlcCer, and has been commercialized as a dietary supplement to improve dry skin and itching that are caused by a deficiency of epidermal ceramide. Nerve growth factor (NGF produced by skin cells is one of the itch factors in the stratum corneum of the skin. Semaphorin 3A (Sema 3A has been known to inhibit NGF-induced neurite outgrowth of epidermal nerve fibers. It is well known that the itch sensation is regulated by the balance between NGF and Sema 3A. In the present study, while kGlcCer did not show an in vitro inhibitory effect on NGF-induced neurite outgrowth of PC12 cells, kCer was demonstrated to inhibit a remarkable neurite outgrowth. In addition, the effect of kCer was similar to that of Sema 3A in cell morphological changes and neurite retractions, but different from C2-Ceramide. kCer showed a Sema 3A-like action, causing CRMP2 phosphorylation, which results in a collapse of neurite growth cones. Thus, it is expected that kCer is an advanced konjac ceramide material that may have neurite outgrowth-specific action to relieve uncontrolled and serious itching, in particular, from atopic eczema.

SemaTyP: a knowledge graph based literature mining method for drug discovery.

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Sang, Shengtian; Yang, Zhihao; Wang, Lei; Liu, Xiaoxia; Lin, Hongfei; Wang, Jian

2018-05-30

Drug discovery is the process through which potential new medicines are identified. High-throughput screening and computer-aided drug discovery/design are the two main drug discovery methods for now, which have successfully discovered a series of drugs. However, development of new drugs is still an extremely time-consuming and expensive process. Biomedical literature contains important clues for the identification of potential treatments. It could support experts in biomedicine on their way towards new discoveries. Here, we propose a biomedical knowledge graph-based drug discovery method called SemaTyP, which discovers candidate drugs for diseases by mining published biomedical literature. We first construct a biomedical knowledge graph with the relations extracted from biomedical abstracts, then a logistic regression model is trained by learning the semantic types of paths of known drug therapies' existing in the biomedical knowledge graph, finally the learned model is used to discover drug therapies for new diseases. The experimental results show that our method could not only effectively discover new drug therapies for new diseases, but also could provide the potential mechanism of action of the candidate drugs. In this paper we propose a novel knowledge graph based literature mining method for drug discovery. It could be a supplementary method for current drug discovery methods.

Peripheral nerve injury fails to induce growth of lesioned ascending dorsal column axons into spinal cord scar tissue expressing the axon repellent Semaphorin3A

NARCIS (Netherlands)

Pasterkamp, R Jeroen; Anderson, Patrick N; Verhaagen, J

We have investigated the hypothesis that the chemorepellent Semaphorin3A may be involved in the failure of axonal regeneration after injury to the ascending dorsal columns of adult rats. Following transection of the thoracic dorsal columns, fibroblasts in the dorsolateral parts of the lesion site

Semaphorin7A promotes tumor growth and exerts a pro-angiogenic effect in macrophages of mammary tumor-bearing mice

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Ramon eGarcia-Areas

2014-02-01

Full Text Available Semaphorins, a large family of molecules involved in the axonal guidance and development of the nervous system, have been recently shown to have both angiogenic and anti-angiogenic properties. Specifically, semaphorin 7A (SEMA7A has been reported to have a chemotactic activity in neurogenesis, and to be an immune modulator via it binding to α1β1integrins. Additionally, SEMA7A has been shown to promote chemotaxis of monocytes, inducing them to produce proinflammatory mediators. In this study we explored the role of SEMA7A in the tumoral context. We show that SEMA7A is highly expressed by DA-3 murine mammary tumor cells in comparison to normal mammary cells (EpH4, and that peritoneal macrophages from mammary tumor-bearing mice also express SEMA7A at higher levels compared to peritoneal macrophages derived from normal control mice. We also show that murine macrophages treated with recombinant murine SEMA7A significantly increased their expression of proangiogenic molecules, such as CXCL2/MIP-2. Gene silencing of SEMA7A in peritoneal elicited macrophages from DA-3 tumor-bearing mice resulted in decreased CXCL2 expression. Mice implanted with SEMA7A silenced tumor cells showed decreased angiogenesis in the tumors compared to the wild type tumors. Furthermore, peritoneal elicited macrophages from mice bearing SEMA7A-silenced tumors produce significantly (p< 0.01 lower levels of angiogenic proteins, such as MIP-2, CXCL1 and MMP-9, compared to macrophages from control DA-3 mammary tumors. We postulate that SEMA7A derived from mammary carcinomas may serve as a monocyte chemoattractant and skew monocytes into a pro-tumorigenic phenotype. A putative relationship between tumor-derived SEMA7A and monocytes could prove valuable in establishing new research avenues towards unraveling important tumor-host immune interactions in breast cancer patients.

Increased urine semaphorin-3A is associated with renal damage in hypertensive patients with chronic kidney disease: a nested case-control study.

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Viazzi, Francesca; Ramesh, Ganesan; Jayakumar, Calpurnia; Leoncini, Giovanna; Garneri, Debora; Pontremoli, Roberto

2015-06-01

Semaphorins are guidance proteins implicated in several processes such as angiogenesis, organogenesis, cell migration, and cytokine release. Experimental studies showed that semaphorin-3a (SEMA3A) administration induces transient massive proteinuria, podocyte foot process effacement and endothelial cell damage in healthy animals. While SEMA3A signaling has been demonstrated to be mechanistically involved in experimental diabetic glomerulopathy and in acute kidney injury, to date its role in human chronic kidney disease (CKD) has not been investigated. To test the hypothesis that SEMA3A may play a role in human CKD, we performed a cross-sectional, nested, case-control study on 151 matched hypertensive patients with and without CKD. SEMA3A was quantified in the urine (USEMA) by ELISA. Glomerular filtration rate was estimated (eGFR) by the CKD-EPI formula and albuminuria was measured as albumin-to-creatinine ratio (ACR). USEMA levels were positively correlated with urine ACR (p = 0.001) and serum creatinine (p < 0.001). USEMA was higher in patients with both components of renal damage as compared to those with only one and those with normal renal function (p < 0.007 and <0.001, respectively). The presence of increased USEMA levels (i.e. top quartile) entailed a fourfold higher risk of combined renal damage (p < 0.001) and an almost twofold higher risk of macroalbuminuria (p = 0.005) or of reduced eGFR, even adjusting for confounding factors (p = 0.002). USEMA is independently associated with CKD in both diabetic and non diabetic hypertensive patients. Further studies may help clarify the mechanisms underlying this association and possibly the pathogenic changes leading to the development of CKD.

Semaphorin6A acts as a gate keeper between the central and the peripheral nervous system

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Sadhu Rejina

2007-12-01

Full Text Available Abstract Background During spinal cord development, expression of chicken SEMAPHORIN6A (SEMA6A is almost exclusively found in the boundary caps at the ventral motor axon exit point and at the dorsal root entry site. The boundary cap cells are derived from a population of late migrating neural crest cells. They form a transient structure at the transition zone between the peripheral nervous system (PNS and the central nervous system (CNS. Ablation of the boundary cap resulted in emigration of motoneurons from the ventral spinal cord along the ventral roots. Based on its very restricted expression in boundary cap cells, we tested for a role of Sema6A as a gate keeper between the CNS and the PNS. Results Downregulation of Sema6A in boundary cap cells by in ovo RNA interference resulted in motoneurons streaming out of the spinal cord along the ventral roots, and in the failure of dorsal roots to form and segregate properly. PlexinAs interact with class 6 semaphorins and are expressed by both motoneurons and sensory neurons. Knockdown of PlexinA1 reproduced the phenotype seen after loss of Sema6A function both at the ventral motor exit point and at the dorsal root entry site of the lumbosacral spinal cord. Loss of either PlexinA4 or Sema6D function had an effect only at the dorsal root entry site but not at the ventral motor axon exit point. Conclusion Sema6A acts as a gate keeper between the PNS and the CNS both ventrally and dorsally. It is required for the clustering of boundary cap cells at the PNS/CNS interface and, thus, prevents motoneurons from streaming out of the ventral spinal cord. At the dorsal root entry site it organizes the segregation of dorsal roots.

Immobilization of chitosan film containing semaphorin 3A onto a microarc oxidized titanium implant surface via silane reaction to improve MG63 osteogenic differentiation

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Fang K

2014-10-01

Full Text Available Kaixiu Fang,1,* Wen Song,2,* Lifeng Wang,1 Sen Jia,3 Hongbo Wei,1 Shuai Ren,1 Xiaoru Xu,1 Yingliang Song1 1State Key Laboratory of Military Stomatology, Department of Implant Dentistry, School of Stomatology, Fourth Military Medical University, Xi’an, People’s Republic of China; 2State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, School of Stomatology, Fourth Military Medical University, Xi’an, People’s Republic of China; 3State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi’an, People’s Republic of China *These authors contributed equally to this work Abstract: Improving osseointegration of extensively used titanium (Ti implants still remains a main theme in implantology. Recently, grafting biomolecules onto a Ti surface has attracted more attention due to their direct participation in the osseointegration process around the implant. Semaphorin 3A (Sema3A is a new proven osteoprotection molecule and is considered to be a promising therapeutic agent in bone diseases, but how to immobilize the protein onto a Ti surface to acquire a long-term effect is poorly defined. In our study, we tried to use chitosan to wrap Sema3A (CS/Sema and connect to the microarc oxidized Ti surface via silane glutaraldehyde coupling. The microarc oxidization could formulate porous topography on a Ti surface, and the covalently bonded coating was homogeneously covered on the ridges between the pores without significant influence on the original topography. A burst release of Sema3A was observed in the first few days in phosphate-buffered saline and could be maintained for >2 weeks. Coating in phosphate-buffered saline containing lysozyme was similar, but the release rate was much more rapid. The coating did not significantly affect cellular adhesion, viability, or cytoskeleton arrangement, but the osteogenic-related gene

High Performance Implementation of 3D Convolutional Neural Networks on a GPU

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Wang, Zelong; Wen, Mei; Zhang, Chunyuan; Wang, Yijie

2017-01-01

Convolutional neural networks have proven to be highly successful in applications such as image classification, object tracking, and many other tasks based on 2D inputs. Recently, researchers have started to apply convolutional neural networks to video classification, which constitutes a 3D input and requires far larger amounts of memory and much more computation. FFT based methods can reduce the amount of computation, but this generally comes at the cost of an increased memory requirement. On the other hand, the Winograd Minimal Filtering Algorithm (WMFA) can reduce the number of operations required and thus can speed up the computation, without increasing the required memory. This strategy was shown to be successful for 2D neural networks. We implement the algorithm for 3D convolutional neural networks and apply it to a popular 3D convolutional neural network which is used to classify videos and compare it to cuDNN. For our highly optimized implementation of the algorithm, we observe a twofold speedup for most of the 3D convolution layers of our test network compared to the cuDNN version. PMID:29250109

High Performance Implementation of 3D Convolutional Neural Networks on a GPU.

Science.gov (United States)

Lan, Qiang; Wang, Zelong; Wen, Mei; Zhang, Chunyuan; Wang, Yijie

2017-01-01

Convolutional neural networks have proven to be highly successful in applications such as image classification, object tracking, and many other tasks based on 2D inputs. Recently, researchers have started to apply convolutional neural networks to video classification, which constitutes a 3D input and requires far larger amounts of memory and much more computation. FFT based methods can reduce the amount of computation, but this generally comes at the cost of an increased memory requirement. On the other hand, the Winograd Minimal Filtering Algorithm (WMFA) can reduce the number of operations required and thus can speed up the computation, without increasing the required memory. This strategy was shown to be successful for 2D neural networks. We implement the algorithm for 3D convolutional neural networks and apply it to a popular 3D convolutional neural network which is used to classify videos and compare it to cuDNN. For our highly optimized implementation of the algorithm, we observe a twofold speedup for most of the 3D convolution layers of our test network compared to the cuDNN version.

Slit/Robo1 signaling regulates neural tube development by balancing neuroepithelial cell proliferation and differentiation

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Wang, Guang; Li, Yan; Wang, Xiao-yu [Key Laboratory for Regenerative Medicine of The Ministry of Education, Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632 (China); Han, Zhe [Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510224 (China); Chuai, Manli [College of Life Sciences Biocentre, University of Dundee, Dundee DD1 5EH (United Kingdom); Wang, Li-jing [Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510224 (China); Ho Lee, Kenneth Ka [Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin (Hong Kong); Geng, Jian-guo, E-mail: jgeng@umich.edu [Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510224 (China); Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109 (United States); Yang, Xuesong, E-mail: yang_xuesong@126.com [Key Laboratory for Regenerative Medicine of The Ministry of Education, Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632 (China)

2013-05-01

Formation of the neural tube is the morphological hallmark for development of the embryonic central nervous system (CNS). Therefore, neural tube development is a crucial step in the neurulation process. Slit/Robo signaling was initially identified as a chemo-repellent that regulated axon growth cone elongation, but its role in controlling neural tube development is currently unknown. To address this issue, we investigated Slit/Robo1 signaling in the development of chick neCollege of Life Sciences Biocentre, University of Dundee, Dundee DD1 5EH, UKural tube and transgenic mice over-expressing Slit2. We disrupted Slit/Robo1 signaling by injecting R5 monoclonal antibodies into HH10 neural tubes to block the Robo1 receptor. This inhibited the normal development of the ventral body curvature and caused the spinal cord to curl up into a S-shape. Next, Slit/Robo1 signaling on one half-side of the chick embryo neural tube was disturbed by electroporation in ovo. We found that the morphology of the neural tube was dramatically abnormal after we interfered with Slit/Robo1 signaling. Furthermore, we established that silencing Robo1 inhibited cell proliferation while over-expressing Robo1 enhanced cell proliferation. We also investigated the effects of altering Slit/Robo1 expression on Sonic Hedgehog (Shh) and Pax7 expression in the developing neural tube. We demonstrated that over-expressing Robo1 down-regulated Shh expression in the ventral neural tube and resulted in the production of fewer HNK-1{sup +} migrating neural crest cells (NCCs). In addition, Robo1 over-expression enhanced Pax7 expression in the dorsal neural tube and increased the number of Slug{sup +} pre-migratory NCCs. Conversely, silencing Robo1 expression resulted in an enhanced Shh expression and more HNK-1{sup +} migrating NCCs but reduced Pax7 expression and fewer Slug{sup +} pre-migratory NCCs were observed. In conclusion, we propose that Slit/Robo1 signaling is involved in regulating neural tube

DNA methyltransferase 3b is dispensable for mouse neural crest development.

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Bridget T Jacques-Fricke

Full Text Available The neural crest is a population of multipotent cells that migrates extensively throughout vertebrate embryos to form diverse structures. Mice mutant for the de novo DNA methyltransferase DNMT3b exhibit defects in two neural crest derivatives, the craniofacial skeleton and cardiac ventricular septum, suggesting that DNMT3b activity is necessary for neural crest development. Nevertheless, the requirement for DNMT3b specifically in neural crest cells, as opposed to interacting cell types, has not been determined. Using a conditional DNMT3b allele crossed to the neural crest cre drivers Wnt1-cre and Sox10-cre, neural crest DNMT3b mutants were generated. In both neural crest-specific and fully DNMT3b-mutant embryos, cranial neural crest cells exhibited only subtle migration defects, with increased numbers of dispersed cells trailing organized streams in the head. In spite of this, the resulting cranial ganglia, craniofacial skeleton, and heart developed normally when neural crest cells lacked DNMT3b. This indicates that DNTM3b is not necessary in cranial neural crest cells for their development. We conclude that defects in neural crest derivatives in DNMT3b mutant mice reflect a requirement for DNMT3b in lineages such as the branchial arch mesendoderm or the cardiac mesoderm that interact with neural crest cells during formation of these structures.

Brief Report: Robo1 Regulates the Migration of Human Subventricular Zone Neural Progenitor Cells During Development.

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Guerrero-Cazares, Hugo; Lavell, Emily; Chen, Linda; Schiapparelli, Paula; Lara-Velazquez, Montserrat; Capilla-Gonzalez, Vivian; Clements, Anna Christina; Drummond, Gabrielle; Noiman, Liron; Thaler, Katrina; Burke, Anne; Quiñones-Hinojosa, Alfredo

2017-07-01

Human neural progenitor cell (NPC) migration within the subventricular zone (SVZ) of the lateral ganglionic eminence is an active process throughout early brain development. The migration of human NPCs from the SVZ to the olfactory bulb during fetal stages resembles what occurs in adult rodents. As the human brain develops during infancy, this migratory stream is drastically reduced in cell number and becomes barely evident in adults. The mechanisms regulating human NPC migration are unknown. The Slit-Robo signaling pathway has been defined as a chemorepulsive cue involved in axon guidance and neuroblast migration in rodents. Slit and Robo proteins expressed in the rodent brain help guide neuroblast migration from the SVZ through the rostral migratory stream to the olfactory bulb. Here, we present the first study on the role that Slit and Robo proteins play in human-derived fetal neural progenitor cell migration (hfNPC). We describe that Robo1 and Robo2 isoforms are expressed in the human fetal SVZ. Furthermore, we demonstrate that Slit2 is able to induce a chemorepellent effect on the migration of hfNPCs derived from the human fetal SVZ. In addition, when Robo1 expression is inhibited, hfNPCs are unable to migrate to the olfactory bulb of mice when injected in the anterior SVZ. Our findings indicate that the migration of human NPCs from the SVZ is partially regulated by the Slit-Robo axis. This pathway could be regulated to direct the migration of NPCs in human endogenous neural cell therapy. Stem Cells 2017;35:1860-1865. © 2017 AlphaMed Press.

Functional similarities between the dictyostelium protein AprA and the human protein dipeptidyl-peptidase IV.

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Herlihy, Sarah E; Tang, Yu; Phillips, Jonathan E; Gomer, Richard H

2017-03-01

Autocrine proliferation repressor protein A (AprA) is a protein secreted by Dictyostelium discoideum cells. Although there is very little sequence similarity between AprA and any human protein, AprA has a predicted structural similarity to the human protein dipeptidyl peptidase IV (DPPIV). AprA is a chemorepellent for Dictyostelium cells, and DPPIV is a chemorepellent for neutrophils. This led us to investigate if AprA and DPPIV have additional functional similarities. We find that like AprA, DPPIV is a chemorepellent for, and inhibits the proliferation of, D. discoideum cells, and that AprA binds some DPPIV binding partners such as fibronectin. Conversely, rAprA has DPPIV-like protease activity. These results indicate a functional similarity between two eukaryotic chemorepellent proteins with very little sequence similarity, and emphasize the usefulness of using a predicted protein structure to search a protein structure database, in addition to searching for proteins with similar sequences. © 2016 The Protein Society.

Functional similarities between the dictyostelium protein AprA and the human protein dipeptidyl‐peptidase IV

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Herlihy, Sarah E.; Tang, Yu; Phillips, Jonathan E.

2017-01-01

Abstract Autocrine proliferation repressor protein A (AprA) is a protein secreted by Dictyostelium discoideum cells. Although there is very little sequence similarity between AprA and any human protein, AprA has a predicted structural similarity to the human protein dipeptidyl peptidase IV (DPPIV). AprA is a chemorepellent for Dictyostelium cells, and DPPIV is a chemorepellent for neutrophils. This led us to investigate if AprA and DPPIV have additional functional similarities. We find that like AprA, DPPIV is a chemorepellent for, and inhibits the proliferation of, D. discoideum cells, and that AprA binds some DPPIV binding partners such as fibronectin. Conversely, rAprA has DPPIV‐like protease activity. These results indicate a functional similarity between two eukaryotic chemorepellent proteins with very little sequence similarity, and emphasize the usefulness of using a predicted protein structure to search a protein structure database, in addition to searching for proteins with similar sequences. PMID:28028841

The neurovascular relation in oxygen-induced retinopathy.

Science.gov (United States)

Akula, James D; Mocko, Julie A; Benador, Ilan Y; Hansen, Ronald M; Favazza, Tara L; Vyhovsky, Tanya C; Fulton, Anne B

2008-01-01

Longitudinal studies in rat models of retinopathy of prematurity (ROP) have demonstrated that abnormalities of retinal vasculature and function change hand-in-hand. In the developing retina, vascular and neural structures are under cooperative molecular control. In this study of rats with oxygen-induced retinopathy (OIR) models of ROP, mRNA expression of vascular endothelial growth factor (VEGF), semaphorin (Sema), and their neuropilin receptor (NRP) were examined during the course of retinopathy to evaluate their roles in the observed neurovascular congruency. Oxygen exposures designed to induce retinopathy were delivered to Sprague-Dawley rat pups (n=36) from postnatal day (P) 0 to P14 or from P7 to P14. Room-air-reared controls (n=18) were also studied. Sensitivities of the rod photoreceptors (S(rod)) and the postreceptor cells (Sm) were derived from electroretinographic (ERG) records. Arteriolar tortuosity, T(A), was derived from digital fundus images using Retinal Image multi-Scale Analysis (RISA) image analysis software. mRNA expression of VEGF(164), semaphorin IIIA (Sema3A), and neuropilin-1 (NRP-1) was evaluated by RT-PCR of retinal extracts. Tests were performed at P15-P16, P18-P19, and P25-P26. Relations among ERG, RISA, and PCR parameters were evaluated using linear regression on log transformed data. Sm was low and T(A) was high at young ages, then both resolved by P25-P26. VEGF(164) and Sema3A mRNA expression were also elevated early and decreased with age. Low Sm was significantly associated with high VEGF(164) and Sema3A expression. Low S(rod) was also significantly associated with high VEGF(164). S(rod) and Sm were both correlated with T(A). NRP-1 expression was little affected by OIR. The postreceptor retina appears to mediate the vascular abnormalities that characterize OIR. Because of the relationships revealed by these data, early treatment that targets the neural retina may mitigate the effects of ROP.

Mechanism of selective VEGF-A binding by neuropilin-1 reveals a basis for specific ligand inhibition.

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Matthew W Parker

Full Text Available Neuropilin (Nrp receptors function as essential cell surface receptors for the Vascular Endothelial Growth Factor (VEGF family of proangiogenic cytokines and the semaphorin 3 (Sema3 family of axon guidance molecules. There are two Nrp homologues, Nrp1 and Nrp2, which bind to both overlapping and distinct members of the VEGF and Sema3 family of molecules. Nrp1 specifically binds the VEGF-A(164/5 isoform, which is essential for developmental angiogenesis. We demonstrate that VEGF-A specific binding is governed by Nrp1 residues in the b1 coagulation factor domain surrounding the invariant Nrp C-terminal arginine binding pocket. Further, we show that Sema3F does not display the Nrp-specific binding to the b1 domain seen with VEGF-A. Engineered soluble Nrp receptor fragments that selectively sequester ligands from the active signaling complex are an attractive modality for selectively blocking the angiogenic and chemorepulsive functions of Nrp ligands. Utilizing the information on Nrp ligand binding specificity, we demonstrate Nrp constructs that specifically sequester Sema3 in the presence of VEGF-A. This establishes that unique mechanisms are used by Nrp receptors to mediate specific ligand binding and that these differences can be exploited to engineer soluble Nrp receptors with specificity for Sema3.

Vesicular trafficking of semaphorin 3A is activity-dependent and differs between axons and dendrites

NARCIS (Netherlands)

de Wit, Joris; Toonen, Ruud F; Verhaagen, J.; Verhage, Matthijs

Secreted semaphorins act as guidance cues in the developing nervous system and may have additional functions in mature neurons. How semaphorins are transported and secreted by neurons is poorly understood. We find that endogenous semaphorin 3A (Sema3A) displays a punctate distribution in axons and

Engineering Human Neural Tissue by 3D Bioprinting.

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Gu, Qi; Tomaskovic-Crook, Eva; Wallace, Gordon G; Crook, Jeremy M

2018-01-01

Bioprinting provides an opportunity to produce three-dimensional (3D) tissues for biomedical research and translational drug discovery, toxicology, and tissue replacement. Here we describe a method for fabricating human neural tissue by 3D printing human neural stem cells with a bioink, and subsequent gelation of the bioink for cell encapsulation, support, and differentiation to functional neurons and supporting neuroglia. The bioink uniquely comprises the polysaccharides alginate, water-soluble carboxymethyl-chitosan, and agarose. Importantly, the method could be adapted to fabricate neural and nonneural tissues from other cell types, with the potential to be applied for both research and clinical product development.

Simbrain 3.0: A flexible, visually-oriented neural network simulator.

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Tosi, Zachary; Yoshimi, Jeffrey

2016-11-01

Simbrain 3.0 is a software package for neural network design and analysis, which emphasizes flexibility (arbitrarily complex networks can be built using a suite of basic components) and a visually rich, intuitive interface. These features support both students and professionals. Students can study all of the major classes of neural networks in a familiar graphical setting, and can easily modify simulations, experimenting with networks and immediately seeing the results of their interventions. With the 3.0 release, Simbrain supports models on the order of thousands of neurons and a million synapses. This allows the same features that support education to support research professionals, who can now use the tool to quickly design, run, and analyze the behavior of large, highly customizable simulations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neural crest stem cell multipotency requires Foxd3 to maintain neural potential and repress mesenchymal fates.

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Mundell, Nathan A; Labosky, Patricia A

2011-02-01

Neural crest (NC) progenitors generate a wide array of cell types, yet molecules controlling NC multipotency and self-renewal and factors mediating cell-intrinsic distinctions between multipotent versus fate-restricted progenitors are poorly understood. Our earlier work demonstrated that Foxd3 is required for maintenance of NC progenitors in the embryo. Here, we show that Foxd3 mediates a fate restriction choice for multipotent NC progenitors with loss of Foxd3 biasing NC toward a mesenchymal fate. Neural derivatives of NC were lost in Foxd3 mutant mouse embryos, whereas abnormally fated NC-derived vascular smooth muscle cells were ectopically located in the aorta. Cranial NC defects were associated with precocious differentiation towards osteoblast and chondrocyte cell fates, and individual mutant NC from different anteroposterior regions underwent fate changes, losing neural and increasing myofibroblast potential. Our results demonstrate that neural potential can be separated from NC multipotency by the action of a single gene, and establish novel parallels between NC and other progenitor populations that depend on this functionally conserved stem cell protein to regulate self-renewal and multipotency.

Requirement for Foxd3 in the maintenance of neural crest progenitors.

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Teng, Lu; Mundell, Nathan A; Frist, Audrey Y; Wang, Qiaohong; Labosky, Patricia A

2008-05-01

Understanding the molecular mechanisms of stem cell maintenance is crucial for the ultimate goal of manipulating stem cells for the treatment of disease. Foxd3 is required early in mouse embryogenesis; Foxd3(-/-) embryos fail around the time of implantation, cells of the inner cell mass cannot be maintained in vitro, and blastocyst-derived stem cell lines cannot be established. Here, we report that Foxd3 is required for maintenance of the multipotent mammalian neural crest. Using tissue-specific deletion of Foxd3 in the neural crest, we show that Foxd3(flox/-); Wnt1-Cre mice die perinatally with a catastrophic loss of neural crest-derived structures. Cranial neural crest tissues are either missing or severely reduced in size, the peripheral nervous system consists of reduced dorsal root ganglia and cranial nerves, and the entire gastrointestinal tract is devoid of neural crest derivatives. These results demonstrate a global role for this transcriptional repressor in all aspects of neural crest maintenance along the anterior-posterior axis, and establish an unprecedented molecular link between multiple divergent progenitor lineages of the mammalian embryo.

Neural engineering from advanced biomaterials to 3D fabrication techniques

CERN Document Server

Kaplan, David

2016-01-01

This book covers the principles of advanced 3D fabrication techniques, stem cells and biomaterials for neural engineering. Renowned contributors cover topics such as neural tissue regeneration, peripheral and central nervous system repair, brain-machine interfaces and in vitro nervous system modeling. Within these areas, focus remains on exciting and emerging technologies such as highly developed neuroprostheses and the communication channels between the brain and prostheses, enabling technologies that are beneficial for development of therapeutic interventions, advanced fabrication techniques such as 3D bioprinting, photolithography, microfluidics, and subtractive fabrication, and the engineering of implantable neural grafts. There is a strong focus on stem cells and 3D bioprinting technologies throughout the book, including working with embryonic, fetal, neonatal, and adult stem cells and a variety of sophisticated 3D bioprinting methods for neural engineering applications. There is also a strong focus on b...

CTNNA3 and SEMA3D

DEFF Research Database (Denmark)

McGeachie, Michael J; Wu, Ann C; Tse, Sze Man

2015-01-01

BACKGROUND: Asthma exacerbations are a major cause of morbidity and medical cost. OBJECTIVE: The objective of this study was to identify genetic predictors of exacerbations in asthmatic subjects. METHODS: We performed a genome-wide association study meta-analysis of acute asthma exacerbation in 2...

The role of semaphorin 4D as a potential biomarker for antiangiogenic therapy in colorectal cancer

Directory of Open Access Journals (Sweden)

Ding X

2016-03-01

Full Text Available Xiaojie Ding,1,2,* Lijuan Qiu,1,2,* Lijuan Zhang,3 Juemin Xi,1,2 Duo Li,1,2 Xinwei Huang,1,2 Yujiao Zhao,1,2 Xiaodang Wang,1,2 Qiangming Sun1,2 1Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 2Molecular Epidemiology Joint Laboratory, Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, 3Department of Pathology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Provincial Tumor Hospital, Kunming, People’s Republic of China*These authors contributed equally to this workBackground: Semaphorin 4D (Sema4D belongs to the class IV semaphorins, and accumulating evidence has indicated that its elevated level may be one strategy by which tumors evade current antiangiogenic therapies. The biological roles of Sema4D in colorectal cancer (CRC, however, remain largely undefined. This study was designed to investigate the effects of Sema4D on tumor angiogenesis and growth in CRC, especially in different vascular endothelial growth factor (VEGF backgrounds.Methods: The expression of Sema4D in human CRC was evaluated by immunohistochemical analysis of tumors and their matching normal control tissues. The expression level of Sema4D and VEGF was investigated in different CRC cell lines. To evaluate the contributions of Sema4D to tumor-induced angiogenesis, two CRC cell lines with opposite VEGF backgrounds were infected with lentiviruses expressing Sema4D or Sema4D short hairpin RNA, followed by in vitro migration and in vivo tumor angiogenic assays.Results: Immunohistochemical analysis of human CRC revealed high levels of Sema4D in a cell surface pattern. In all, 84.85% of CRC samples analyzed exhibited moderate to strong Sema4D expression. The positive ratios of Sema4D staining for well, moderately, and poorly differentiated cancers were 71.43%, 96.67%, and 77.27%, respectively. Sema4D is highly expressed in five different CRC cell lines, while VEGF

Regulation of semaphorin 4D expression and cell proliferation of ovarian cancer by ERalpha and ERbeta

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Y. Liu

Full Text Available Ovarian cancer is one of the most common malignancies in women. Semaphorin 4D (sema 4D is involved in the progress of multiple cancers. In the presence of estrogen-like ligands, estrogen receptors (ERα and ERβ participate in the progress of breast and ovarian cancers by transcriptional regulation. The aim of the study was to investigate the role of sema 4D and elucidate the regulatory pattern of ERα and ERβ on sema 4D expression in ovarian cancers. Sema 4D levels were up-regulated in ovarian cancer SKOV-3 cells. Patients with malignant ovarian cancers had significantly higher sema 4D levels than controls, suggesting an oncogene role of sema 4D in ovarian cancer. ERα expressions were up-regulated in SKOV-3 cells compared with normal ovarian IOSE80 epithelial cells. Conversely, down-regulation of ERβ was observed in SKOV-3 cells. Forced over-expression of ERα and ERβ in SKOV-3 cells was manipulated to establish ERα+ and ERβ+ SKOV-3 cell lines. Incubation of ERα+ SKOV-3 cells with ERs agonist 17β-estradiol (E2 significantly enhanced sema 4D expression and rate of cell proliferation. Incubated with E2, ERβ+ SKOV-3 cells showed lower sema 4D expression and cell proliferation. Blocking ERα and ERβ activities with ICI182-780 inhibitor, sema 4D expressions and cell proliferation of ERα+ and ERβ+ SKOV-3 cells were recovered to control levels. Taken together, the data showed that sema 4D expression was positively correlated with the progress of ovarian cancer. ERα positively regulated sema 4D expression and accelerated cell proliferation. ERβ negatively regulated sema 4D expression and inhibited cell multiplication.

3D silicon neural probe with integrated optical fibers for optogenetic modulation.

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Kim, Eric G R; Tu, Hongen; Luo, Hao; Liu, Bin; Bao, Shaowen; Zhang, Jinsheng; Xu, Yong

2015-07-21

Optogenetics is a powerful modality for neural modulation that can be useful for a wide array of biomedical studies. Penetrating microelectrode arrays provide a means of recording neural signals with high spatial resolution. It is highly desirable to integrate optics with neural probes to allow for functional study of neural tissue by optogenetics. In this paper, we report the development of a novel 3D neural probe coupled simply and robustly to optical fibers using a hollow parylene tube structure. The device shanks are hollow tubes with rigid silicon tips, allowing the insertion and encasement of optical fibers within the shanks. The position of the fiber tip can be precisely controlled relative to the electrodes on the shank by inherent design features. Preliminary in vivo rat studies indicate that these devices are capable of optogenetic modulation simultaneously with 3D neural signal recording.

Brain endothelial cells control fertility through ovarian-steroid-dependent release of semaphorin 3A

NARCIS (Netherlands)

Giacobini, Paolo; Parkash, Jyoti; Campagne, Céline; Messina, Andrea; Casoni, Filippo; Vanacker, Charlotte; Langlet, Fanny; Hobo, Barbara; Cagnoni, Gabriella; Gallet, Sarah; Hanchate, Naresh Kumar; Mazur, Danièle; Taniguchi, Masahiko; Mazzone, Massimiliano; Verhaagen, J.; Ciofi, Philippe; Bouret, Sébastien G; Tamagnone, Luca; Prevot, Vincent

Neuropilin-1 (Nrp1) guides the development of the nervous and vascular systems, but its role in the mature brain remains to be explored. Here we report that the expression of the 65 kDa isoform of Sema3A, the ligand of Nrp1, by adult vascular endothelial cells, is regulated during the ovarian cycle

Gelatin methacrylamide hydrogel with graphene nanoplatelets for neural cell-laden 3D bioprinting.

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Wei Zhu; Harris, Brent T; Zhang, Lijie Grace

2016-08-01

Nervous system is extremely complex which leads to rare regrowth of nerves once injury or disease occurs. Advanced 3D bioprinting strategy, which could simultaneously deposit biocompatible materials, cells and supporting components in a layer-by-layer manner, may be a promising solution to address neural damages. Here we presented a printable nano-bioink composed of gelatin methacrylamide (GelMA), neural stem cells, and bioactive graphene nanoplatelets to target nerve tissue regeneration in the assist of stereolithography based 3D bioprinting technique. We found the resultant GelMA hydrogel has a higher compressive modulus with an increase of GelMA concentration. The porous GelMA hydrogel can provide a biocompatible microenvironment for the survival and growth of neural stem cells. The cells encapsulated in the hydrogel presented good cell viability at the low GelMA concentration. Printed neural construct exhibited well-defined architecture and homogenous cell distribution. In addition, neural stem cells showed neuron differentiation and neurites elongation within the printed construct after two weeks of culture. These findings indicate the 3D bioprinted neural construct has great potential for neural tissue regeneration.

Comparison of 2D and 3D neural induction methods for the generation of neural progenitor cells from human induced pluripotent stem cells

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Chandrasekaran, Abinaya; Avci, Hasan; Ochalek, Anna

2017-01-01

Neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) are frequently induced using 3D culture methodologies however, it is unknown whether spheroid-based (3D) neural induction is actually superior to monolayer (2D) neural induction. Our aim was to compare the efficiency......), cortical layer (TBR1, CUX1) and glial markers (SOX9, GFAP, AQP4). Electron microscopy demonstrated that both methods resulted in morphologically similar neural rosettes. However, quantification of NPCs derived from 3D neural induction exhibited an increase in the number of PAX6/NESTIN double positive cells...... the electrophysiological properties between the two induction methods. In conclusion, 3D neural induction increases the yield of PAX6+/NESTIN+ cells and gives rise to neurons with longer neurites, which might be an advantage for the production of forebrain cortical neurons, highlighting the potential of 3D neural...

Neural tube closure depends on expression of Grainyhead-like 3 in multiple tissues.

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De Castro, Sandra C P; Hirst, Caroline S; Savery, Dawn; Rolo, Ana; Lickert, Heiko; Andersen, Bogi; Copp, Andrew J; Greene, Nicholas D E

2018-03-15

Failure of neural tube closure leads to neural tube defects (NTDs), common congenital abnormalities in humans. Among the genes whose loss of function causes NTDs in mice, Grainyhead-like3 (Grhl3) is essential for spinal neural tube closure, with null mutants exhibiting fully penetrant spina bifida. During spinal neurulation Grhl3 is initially expressed in the surface (non-neural) ectoderm, subsequently in the neuroepithelial component of the neural folds and at the node-streak border, and finally in the hindgut endoderm. Here, we show that endoderm-specific knockout of Grhl3 causes late-arising spinal NTDs, preceded by increased ventral curvature of the caudal region which was shown previously to suppress closure of the spinal neural folds. This finding supports the hypothesis that diminished Grhl3 expression in the hindgut is the cause of spinal NTDs in the curly tail, carrying a hypomorphic Grhl3 allele. Complete loss of Grhl3 function produces a more severe phenotype in which closure fails earlier in neurulation, before the stage of onset of expression in the hindgut of wild-type embryos. This implicates additional tissues and NTD mechanisms in Grhl3 null embryos. Conditional knockout of Grhl3 in the neural plate and node-streak border has minimal effect on closure, suggesting that abnormal function of surface ectoderm, where Grhl3 transcripts are first detected, is primarily responsible for early failure of spinal neurulation in Grhl3 null embryos. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Semaphorin 5A inhibits synaptogenesis in early postnatal- and adult-born hippocampal dentate granule cells.

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Duan, Yuntao; Wang, Shih-Hsiu; Song, Juan; Mironova, Yevgeniya; Ming, Guo-li; Kolodkin, Alex L; Giger, Roman J

2014-10-14

Human SEMAPHORIN 5A (SEMA5A) is an autism susceptibility gene; however, its function in brain development is unknown. In this study, we show that mouse Sema5A negatively regulates synaptogenesis in early, developmentally born, hippocampal dentate granule cells (GCs). Sema5A is strongly expressed by GCs and regulates dendritic spine density in a cell-autonomous manner. In the adult mouse brain, newly born Sema5A-/- GCs show an increase in dendritic spine density and increased AMPA-type synaptic responses. Sema5A signals through PlexinA2 co-expressed by GCs, and the PlexinA2-RasGAP activity is necessary to suppress spinogenesis. Like Sema5A-/- mutants, PlexinA2-/- mice show an increase in GC glutamatergic synapses, and we show that Sema5A and PlexinA2 genetically interact with respect to GC spine phenotypes. Sema5A-/- mice display deficits in social interaction, a hallmark of autism-spectrum-disorders. These experiments identify novel intra-dendritic Sema5A/PlexinA2 interactions that inhibit excitatory synapse formation in developmentally born and adult-born GCs, and they provide support for SEMA5A contributions to autism-spectrum-disorders.

Connexin 43-mediated modulation of polarized cell movement and the directional migration of cardiac neural crest cells.

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Xu, Xin; Francis, Richard; Wei, Chih Jen; Linask, Kaari L; Lo, Cecilia W

2006-09-01

Connexin 43 knockout (Cx43alpha1KO) mice have conotruncal heart defects that are associated with a reduction in the abundance of cardiac neural crest cells (CNCs) targeted to the heart. In this study, we show CNCs can respond to changing fibronectin matrix density by adjusting their migratory behavior, with directionality increasing and speed decreasing with increasing fibronectin density. However, compared with wild-type CNCs, Cx43alpha1KO CNCs show reduced directionality and speed, while CNCs overexpressing Cx43alpha1 from the CMV43 transgenic mice show increased directionality and speed. Altered integrin signaling was indicated by changes in the distribution of vinculin containing focal contacts, and altered temporal response of Cx43alpha1KO and CMV43 CNCs to beta1 integrin function blocking antibody treatment. High resolution motion analysis showed Cx43alpha1KO CNCs have increased cell protrusive activity accompanied by the loss of polarized cell movement. They exhibited an unusual polygonal arrangement of actin stress fibers that indicated a profound change in cytoskeletal organization. Semaphorin 3A, a chemorepellent known to inhibit integrin activation, was found to inhibit CNC motility, but in the Cx43alpha1KO and CMV43 CNCs, cell processes failed to retract with semaphorin 3A treatment. Immunohistochemical and biochemical analyses suggested close interactions between Cx43alpha1, vinculin and other actin-binding proteins. However, dye coupling analysis showed no correlation between gap junction communication level and fibronectin plating density. Overall, these findings indicate Cx43alpha1 may have a novel function in mediating crosstalk with cell signaling pathways that regulate polarized cell movement essential for the directional migration of CNCs.

Tailor-made conductive inks from cellulose nanofibrils for 3D printing of neural guidelines.

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Kuzmenko, Volodymyr; Karabulut, Erdem; Pernevik, Elin; Enoksson, Peter; Gatenholm, Paul

2018-06-01

Neural tissue engineering (TE), an innovative biomedical method of brain study, is very dependent on scaffolds that support cell development into a functional tissue. Recently, 3D patterned scaffolds for neural TE have shown significant positive effects on cells by a more realistic mimicking of actual neural tissue. In this work, we present a conductive nanocellulose-based ink for 3D printing of neural TE scaffolds. It is demonstrated that by using cellulose nanofibrils and carbon nanotubes as ink constituents, it is possible to print guidelines with a diameter below 1 mm and electrical conductivity of 3.8 × 10 -1  S cm -1 . The cell culture studies reveal that neural cells prefer to attach, proliferate, and differentiate on the 3D printed conductive guidelines. To our knowledge, this is the first research effort devoted to using cost-effective cellulosic 3D printed structures in neural TE, and we suppose that much more will arise in the near future. Copyright © 2018 Elsevier Ltd. All rights reserved.

3D Polygon Mesh Compression with Multi Layer Feed Forward Neural Networks

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Emmanouil Piperakis

2003-06-01

Full Text Available In this paper, an experiment is conducted which proves that multi layer feed forward neural networks are capable of compressing 3D polygon meshes. Our compression method not only preserves the initial accuracy of the represented object but also enhances it. The neural network employed includes the vertex coordinates, the connectivity and normal information in one compact form, converting the discrete and surface polygon representation into an analytic, solid colloquial. Furthermore, the 3D object in its compressed neural form can be directly - without decompression - used for rendering. The neural compression - representation is viable to 3D transformations without the need of any anti-aliasing techniques - transformations do not disrupt the accuracy of the geometry. Our method does not su.er any scaling problem and was tested with objects of 300 to 107 polygons - such as the David of Michelangelo - achieving in all cases an order of O(b3 less bits for the representation than any other commonly known compression method. The simplicity of our algorithm and the established mathematical background of neural networks combined with their aptness for hardware implementation can establish this method as a good solution for polygon compression and if further investigated, a novel approach for 3D collision, animation and morphing.

Comparison of 2D and 3D neural induction methods for the generation of neural progenitor cells from human induced pluripotent stem cells.

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Chandrasekaran, Abinaya; Avci, Hasan X; Ochalek, Anna; Rösingh, Lone N; Molnár, Kinga; László, Lajos; Bellák, Tamás; Téglási, Annamária; Pesti, Krisztina; Mike, Arpad; Phanthong, Phetcharat; Bíró, Orsolya; Hall, Vanessa; Kitiyanant, Narisorn; Krause, Karl-Heinz; Kobolák, Julianna; Dinnyés, András

2017-12-01

Neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) are frequently induced using 3D culture methodologies however, it is unknown whether spheroid-based (3D) neural induction is actually superior to monolayer (2D) neural induction. Our aim was to compare the efficiency of 2D induction with 3D induction method in their ability to generate NPCs, and subsequently neurons and astrocytes. Neural differentiation was analysed at the protein level qualitatively by immunocytochemistry and quantitatively by flow cytometry for NPC (SOX1, PAX6, NESTIN), neuronal (MAP2, TUBB3), cortical layer (TBR1, CUX1) and glial markers (SOX9, GFAP, AQP4). Electron microscopy demonstrated that both methods resulted in morphologically similar neural rosettes. However, quantification of NPCs derived from 3D neural induction exhibited an increase in the number of PAX6/NESTIN double positive cells and the derived neurons exhibited longer neurites. In contrast, 2D neural induction resulted in more SOX1 positive cells. While 2D monolayer induction resulted in slightly less mature neurons, at an early stage of differentiation, the patch clamp analysis failed to reveal any significant differences between the electrophysiological properties between the two induction methods. In conclusion, 3D neural induction increases the yield of PAX6 + /NESTIN + cells and gives rise to neurons with longer neurites, which might be an advantage for the production of forebrain cortical neurons, highlighting the potential of 3D neural induction, independent of iPSCs' genetic background. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

3D bioprinting: A new insight into the therapeutic strategy of neural tissue regeneration.

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Hsieh, Fu-Yu; Hsu, Shan-hui

2015-01-01

Acute traumatic injuries and chronic degenerative diseases represent the world's largest unmet medical need. There are over 50 million people worldwide suffering from neurodegenerative diseases. However, there are only a few treatment options available for acute traumatic injuries and neurodegenerative diseases. Recently, 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. In this commentary, the newly developed 3D bioprinting technique involving neural stem cells (NSCs) embedded in the thermoresponsive biodegradable polyurethane (PU) bioink is reviewed. The thermoresponsive and biodegradable PU dispersion can form gel near 37 °C without any crosslinker. NSCs embedded within the water-based PU hydrogel with appropriate stiffness showed comparable viability and differentiation after printing. Moreover, in the zebrafish embryo neural deficit model, injection of the NSC-laden PU hydrogels promoted the repair of damaged CNS. In addition, the function of adult zebrafish with traumatic brain injury was rescued after implantation of the 3D-printed NSC-laden constructs. Therefore, the newly developed 3D bioprinting technique may offer new possibilities for future therapeutic strategy of neural tissue regeneration.

Influence of neural adaptation on dynamics and equilibrium state of neural activities in a ring neural network

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Takiyama, Ken

2017-12-01

How neural adaptation affects neural information processing (i.e. the dynamics and equilibrium state of neural activities) is a central question in computational neuroscience. In my previous works, I analytically clarified the dynamics and equilibrium state of neural activities in a ring-type neural network model that is widely used to model the visual cortex, motor cortex, and several other brain regions. The neural dynamics and the equilibrium state in the neural network model corresponded to a Bayesian computation and statistically optimal multiple information integration, respectively, under a biologically inspired condition. These results were revealed in an analytically tractable manner; however, adaptation effects were not considered. Here, I analytically reveal how the dynamics and equilibrium state of neural activities in a ring neural network are influenced by spike-frequency adaptation (SFA). SFA is an adaptation that causes gradual inhibition of neural activity when a sustained stimulus is applied, and the strength of this inhibition depends on neural activities. I reveal that SFA plays three roles: (1) SFA amplifies the influence of external input in neural dynamics; (2) SFA allows the history of the external input to affect neural dynamics; and (3) the equilibrium state corresponds to the statistically optimal multiple information integration independent of the existence of SFA. In addition, the equilibrium state in a ring neural network model corresponds to the statistically optimal integration of multiple information sources under biologically inspired conditions, independent of the existence of SFA.

A 3D human neural cell culture system for modeling Alzheimer’s disease

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Kim, Young Hye; Choi, Se Hoon; D’Avanzo, Carla; Hebisch, Matthias; Sliwinski, Christopher; Bylykbashi, Enjana; Washicosky, Kevin J.; Klee, Justin B.; Brüstle, Oliver; Tanzi, Rudolph E.; Kim, Doo Yeon

2015-01-01

Stem cell technologies have facilitated the development of human cellular disease models that can be used to study pathogenesis and test therapeutic candidates. These models hold promise for complex neurological diseases such as Alzheimer’s disease (AD) because existing animal models have been unable to fully recapitulate all aspects of pathology. We recently reported the characterization of a novel three-dimensional (3D) culture system that exhibits key events in AD pathogenesis, including extracellular aggregation of β-amyloid and accumulation of hyperphosphorylated tau. Here we provide instructions for the generation and analysis of 3D human neural cell cultures, including the production of genetically modified human neural progenitor cells (hNPCs) with familial AD mutations, the differentiation of the hNPCs in a 3D matrix, and the analysis of AD pathogenesis. The 3D culture generation takes 1–2 days. The aggregation of β-amyloid is observed after 6-weeks of differentiation followed by robust tau pathology after 10–14 weeks. PMID:26068894

A new neural net approach to robot 3D perception and visuo-motor coordination

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Lee, Sukhan

1992-01-01

A novel neural network approach to robot hand-eye coordination is presented. The approach provides a true sense of visual error servoing, redundant arm configuration control for collision avoidance, and invariant visuo-motor learning under gazing control. A 3-D perception network is introduced to represent the robot internal 3-D metric space in which visual error servoing and arm configuration control are performed. The arm kinematic network performs the bidirectional association between 3-D space arm configurations and joint angles, and enforces the legitimate arm configurations. The arm kinematic net is structured by a radial-based competitive and cooperative network with hierarchical self-organizing learning. The main goal of the present work is to demonstrate that the neural net representation of the robot 3-D perception net serves as an important intermediate functional block connecting robot eyes and arms.

Synapsin III Acts Downstream of Semaphorin 3A/CDK5 Signaling to Regulate Radial Migration and Orientation of Pyramidal Neurons In Vivo

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Laura E. Perlini

2015-04-01

Full Text Available Synapsin III (SynIII is a phosphoprotein that is highly expressed at early stages of neuronal development. Whereas in vitro evidence suggests a role for SynIII in neuronal differentiation, in vivo evidence is lacking. Here, we demonstrate that in vivo downregulation of SynIII expression affects neuronal migration and orientation. By contrast, SynIII overexpression affects neuronal migration, but not orientation. We identify a cyclin-dependent kinase-5 (CDK5 phosphorylation site on SynIII and use phosphomutant rescue experiments to demonstrate its role in SynIII function. Finally, we show that SynIII phosphorylation at the CDK5 site is induced by activation of the semaphorin-3A (Sema3A pathway, which is implicated in migration and orientation of cortical pyramidal neurons (PNs and is known to activate CDK5. Thus, fine-tuning of SynIII expression and phosphorylation by CDK5 activation through Sema3A activity is essential for proper neuronal migration and orientation.

Evaluation of a Standardized Extract from Morus alba against α-Glucosidase Inhibitory Effect and Postprandial Antihyperglycemic in Patients with Impaired Glucose Tolerance: A Randomized Double-Blind Clinical Trial

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Hwang, Seung Hwan; Li, Hong Mei; Wang, Zhiqiang

2016-01-01

To evaluate the antihyperglycemic effect of a standardized extract of the leaves of Morus alba (SEMA), the present study was designed to investigate the α-glucosidase inhibitory effect and acute single oral toxicity as well as evaluate blood glucose reduction in animals and in patients with impaired glucose tolerance in a randomized double-blind clinical trial. SEMA was found to inhibit α-glucosidase at a fourfold higher level than the positive control (acarbose), in a concentration-dependent manner. Moreover, blood glucose concentration was suppressed by SEMA in vivo. Clinical signs and weight changes were observed when conducting an evaluation of the acute toxicity of SEMA through a single-time administration, with clinical observation conducted more than once each day. After administration of the SEMA, observation was for 14 days; all of the animals did not die and did not show any abnormal symptoms. In addition, the inhibitory effects of rice coated with SEMA were evaluated in a group of impaired glucose tolerance patients on postprandial glucose and a group of normal persons, and results showed that SEMA had a clear inhibitory effect on postprandial hyperglycemia in both groups. Overall, SEMA showed excellent potential in the present study as a material for improving postprandial hyperglycemia. PMID:27974904

Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the peripheral nervous system of developing red seabream (Pagrus major)

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Iida, Midori [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Kim, Eun-Young [Department of Life and Nanopharmaceutical Science and Department of Biology, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Murakami, Yasunori [Graduate School of Science and Engineering, Ehime University, Matsuyama 790-8577 (Japan); Shima, Yasuhiro [National Research Institute of Fisheries and Environment of Inland Sea, Fisheries Research Agency, Imabari 794-2305 (Japan); Iwata, Hisato, E-mail: iwatah@agr.ehime-u.ac.jp [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan)

2013-03-15

We investigated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced effects on the morphology of peripheral nervous system (PNS) in the developing red seabream (Pagrus major) embryos. The embryos at 10 h post-fertilization (hpf) were treated with 0, 0.1, 0.4 or 1.7 μg/L of TCDD in seawater for 80 min. The morphology of PNS was microscopically observed with florescence staining using an anti-acetylated tubulin antibody at 48, 78, 120 and 136 hpf. Axon length of facial nerve (VII) was found to be shortened by TCDD exposure. Axon guidance in the glossopharyngeal nerve (IX) and vagus nerve (X) was altered at 120 and 136 hpf in a TCDD dose-dependent manner. Lowest observable effect level of TCDD (0.1 μg/L) that induced the morphological alteration of PNS was lower than those of other endpoints on morphological deformities so far reported. Given that the growth cone at the tip of growing nerve axons advances under the influence of its surrounding tissues, we hypothesized that TCDD exposure would affect (1) the nerve cell proliferation/differentiation, (2) the structure of muscle as an axon target and (3) the nerve guidance factor in the embryos. By the immunostaining of embryos with an antibody against the neuronal specific RNA-binding protein, HuD, and an antibody against the sarcomeric myosin, no morphological effects were observed on the neural proliferation/differentiation and the structure of facial muscles of TCDD-treated embryos. In contrast, whole mount in situ hybridization of semaphorin 3A (Sema3A), a secretory axon repulsion factor, revealed the altered expression pattern of its transcripts in TCDD-treated embryos. Our findings suggest that TCDD treatment affects the projection of PNS in the developing red seabream embryos through the effects on the axonal growth cone guidance molecule such as Sema3A, but not on the neuronal differentiation/proliferation and axon target. The PNS in developing embryos may be one of the most sensitive biomarkers to the exposure

Fabrication of a Highly Aligned Neural Scaffold via a Table Top Stereolithography 3D Printing and Electrospinning.

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Lee, Se-Jun; Nowicki, Margaret; Harris, Brent; Zhang, Lijie Grace

2017-06-01

Three-dimensional (3D) bioprinting is a rapidly emerging technique in the field of tissue engineering to fabricate extremely intricate and complex biomimetic scaffolds in the range of micrometers. Such customized 3D printed constructs can be used for the regeneration of complex tissues such as cartilage, vessels, and nerves. However, the 3D printing techniques often offer limited control over the resolution and compromised mechanical properties due to short selection of printable inks. To address these limitations, we combined stereolithography and electrospinning techniques to fabricate a novel 3D biomimetic neural scaffold with a tunable porous structure and embedded aligned fibers. By employing two different types of biofabrication methods, we successfully utilized both synthetic and natural materials with varying chemical composition as bioink to enhance biocompatibilities and mechanical properties of the scaffold. The resulting microfibers composed of polycaprolactone (PCL) polymer and PCL mixed with gelatin were embedded in 3D printed hydrogel scaffold. Our results showed that 3D printed scaffolds with electrospun fibers significantly improve neural stem cell adhesion when compared to those without the fibers. Furthermore, 3D scaffolds embedded with aligned fibers showed an enhancement in cell proliferation relative to bare control scaffolds. More importantly, confocal microscopy images illustrated that the scaffold with PCL/gelatin fibers greatly increased the average neurite length and directed neurite extension of primary cortical neurons along the fiber. The results of this study demonstrate the potential to create unique 3D neural tissue constructs by combining 3D bioprinting and electrospinning techniques.

Fundamental study of interpretation technique for 3-D magnetotelluric data using neural networks; Neural network wo mochiita sanjigen MT ho data kaishaku gijutsu no kisoteki kenkyu

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Kobayashi, T; Fukuoka, K; Shima, H [Oyo Corp., Tokyo (Japan); Mogi, T [Kyushu University, Fukuoka (Japan). Faculty of Engineering; Spichak, V

1997-05-27

The research and development have been conducted to apply neural networks to interpretation technique for 3-D MT data. In this study, a data base of various data was made from the numerical modeling of 3-D fault model, and the data base management system was constructed. In addition, an unsupervised neural network for treating noise and a supervised neural network for estimating fault parameters such as dip, strike and specific resistance were made, and a basic neural network system was constructed. As a result of the application to the various data, basically sufficient performance for estimating the fault parameters was confirmed. Thus, the optimum MT data for this system were selected. In future, it is necessary to investigate the optimum model and the number of models for learning these neural networks. 3 refs., 5 figs., 2 tabs.

Kinematic Analysis of 3-DOF Planer Robot Using Artificial Neural Network

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Jolly Atit Shah

2012-07-01

Full Text Available Automatic control of the robotic manipulator involves study of kinematics and dynamics as a major issue. This paper involves the forward and inverse kinematics of 3-DOF robotic manipulator with revolute joints. In this study the Denavit- Hartenberg (D-H model is used to model robot links and joints. Also forward and inverse kinematics solution has been achieved using Artificial Neural Networks for 3-DOF robotic manipulator. It shows that by using artificial neural network the solution we get is faster, acceptable and has zero error.

Semaphorin-1a is required for Aedes aegypti embryonic nerve cord development.

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Morgan Haugen

Full Text Available Although mosquito genome projects have uncovered orthologues of many known developmental regulatory genes, extremely little is known about mosquito development. In this study, the role of semaphorin-1a (sema1a was investigated during vector mosquito embryonic ventral nerve cord development. Expression of sema1a and the plexin A (plexA receptor are detected in the embryonic ventral nerve cords of Aedes aegypti (dengue vector and Anopheles gambiae (malaria vector, suggesting that Sema1a signaling may regulate mosquito nervous system development. Analysis of sema1a function was investigated through siRNA-mediated knockdown in A. aegypti embryos. Knockdown of sema1a during A. aegypti development results in a number of nerve cord phenotypes, including thinning, breakage, and occasional fusion of the longitudinal connectives, thin or absent commissures, and general distortion of the nerve cord. Although analysis of Drosophila melanogaster sema1a loss-of-function mutants uncovered many similar phenotypes, aspects of the longitudinal phenotypes differed between D. melanogaster and A. aegypti. The results of this investigation suggest that Sema1a is required for development of the insect ventral nerve cord, but that the developmental roles of this guidance molecule have diverged in dipteran insects.

Expression of neuroimmune semaphorins 4A and 4D and their receptors in the lung is enhanced by allergen and vascular endothelial growth factor

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Keegan Achsah D

2011-05-01

Full Text Available Abstract Background Semaphorins were originally identified as molecules regulating a functional activity of axons in the nervous system. Sema4A and Sema4D were the first semaphorins found to be expressed on immune cells and were termed "immune semaphorins". It is known that Sema4A and Sema4D bind Tim-2 and CD72 expressed on leukocytes and PlexinD1 and B1 present on non-immune cells. These neuroimmune semaphorins and their receptors have been shown to play critical roles in many physiological and pathological processes including neuronal development, immune response regulation, cancer, autoimmune, cardiovascular, renal, and infectious diseases. However, the expression and regulation of Sema4A, Sema4D, and their receptors in normal and allergic lungs is undefined. Results Allergen treatment and lung-specific vascular endothelial growth factor (VEGF expression induced asthma-like pathologies in the murine lungs. These experimental models of allergic airway inflammation were used for the expression analysis of immune semaphorins and their receptors employing immunohistochemistry and flow cytometry techniques. We found that besides accessory-like cells, Sema4A was also detected on bronchial epithelial and smooth muscle cells, whereas Sema4D expression was high on immune cells such as T and B lymphocytes. Surprisingly, under inflammation various cell types including macrophages, lymphocytes, and granulocytes in the lung expressed Tim-2, a previously defined marker for Th2 cells. CD72 was found on lung immune, inflammatory, and epithelial cells. Bronchial epithelial cells were positive for both plexins, whereas some endothelial cells selectively expressed Plexin D1. Plexin B1 expression was also detected on lung DC. Both allergen and VEGF upregulated the expression of neuroimmune semaphorins and their receptors in the lung tissue. However, the lung tissue Sema4A-Tim2 expression was rather weak, whereas Sema4D-CD72 ligand-receptor pair was vastly

Poly(3,4-ethylene dioxythiophene (PEDOT as a micro-neural interface material for electrostimulation

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Seth J Wilks

2009-06-01

Full Text Available Chronic microstimulation-based devices are being investigated to treat conditions such as blindness, deafness, pain, paralysis and epilepsy. Small area electrodes are desired to achieve high selectivity. However, a major trade-off with electrode miniaturization is an increase in impedance and charge density requirements. Thus, the development of novel materials with lower interfacial impedance and enhanced charge storage capacity is essential for the development of micro-neural interface-based neuroprostheses. In this report, we study the use of conducting polymer poly(3,4-ethylene dioxythiophene (PEDOT as a neural interface material for microstimulation of small area iridium electrodes on silicon-substrate arrays. Characterized by electrochemical impedance spectroscopy, electrodeposition of PEDOT results in lower interfacial impedance at physiologically-relevant frequencies, with the 1kHz impedance magnitude being 23.3 ± 0.7 kΩ compared to 113.6 ± 3.5 kΩ for iridium oxide (IrOx on 177μm2 sites. Further, PEDOT exhibits enhanced charge storage capacity at 75.6 ± 5.4 mC/cm2 compared to 28.8 ± 0.3 mC/cm2 for IrOx, characterized by cyclic voltammetry (50 mV/s. These improvements at the electrode interface were corroborated by observation of the voltage excursions that result from constant current pulsing. The PEDOT coatings provide both a lower amplitude voltage and a more ohmic representation of the applied current compared to IrOx. During repetitive pulsing, PEDOT-coated electrodes show stable performance and little change in electrical properties, even at relatively high current densities which cause IrOx instability. These findings support the potential of PEDOT coatings as a micro-neural interface material for electrostimulation.

Semaphorin 4D induces vaginal epithelial cell apoptosis to control mouse postnatal vaginal tissue remodeling.

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Ito, Takuji; Bai, Tao; Tanaka, Tetsuji; Yoshida, Kenji; Ueyama, Takashi; Miyajima, Masayasu; Negishi, Takayuki; Kawasaki, Takahiko; Takamatsu, Hyota; Kikutani, Hitoshi; Kumanogoh, Atsushi; Yukawa, Kazunori

2015-02-01

The opening of the mouse vaginal cavity to the skin is a postnatal tissue remodeling process that occurs at approximately five weeks of age for the completion of female genital tract maturation at puberty. The tissue remodeling process is primarily composed of a hormonally triggered apoptotic process predominantly occurring in the epithelium of the distal section of the vaginal cavity. However, the detailed mechanism underlying the apoptotic induction remains to be elucidated. In the present study, it was observed that the majority of BALB/c mice lacking the class 4 semaphorin, semaphorin 4D (Sema4D), developed imperforate vagina and hydrometrocolpos resulting in a perpetually unopened vaginal cavity regardless of a normal estrogen level comparable with that in wild‑type (WT) mice. Administration of β‑estradiol to infant Sema4D‑deficient (Sema4D‑/‑) mice did not induce precocious vaginal opening, which was observed in WT mice subjected to the same β‑estradiol administration, excluding the possibility that the closed vaginal phenotype was due to insufficient estrogen secretion at the time of vaginal opening. In order to assess the role of Sema4D in the postnatal vaginal tissue remodeling process, the expression of Sema4D and its receptor, plexin‑B1, was examined as well as the level of apoptosis in the vaginal epithelia of five‑week‑old WT and Sema4D‑/‑ mice. Immunohistochemical analyses confirmed the localization of Sema4D and plexin‑B1 in the mouse vaginal epithelia. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and immunohistochemistry detecting activated caspase‑3 revealed significantly fewer apoptotic cells in situ in the vaginal mucosa of five‑week‑old Sema4D‑/‑ mice compared with WT mice. The addition of recombinant Sema4D to Sema4D‑/‑ vaginal epithelial cells in culture significantly enhanced apoptosis of the vaginal epithelial cells, demonstrating the apoptosis‑inducing activity of Sema4D. The

Semaphorin 4D induces vaginal epithelial cell apoptosis to control mouse postnatal vaginal tissue remodeling

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ITO, TAKUJI; BAI, TAO; TANAKA, TETSUJI; YOSHIDA, KENJI; UEYAMA, TAKASHI; MIYAJIMA, MASAYASU; NEGISHI, TAKAYUKI; KAWASAKI, TAKAHIKO; TAKAMATSU, HYOTA; KIKUTANI, HITOSHI; KUMANOGOH, ATSUSHI; YUKAWA, KAZUNORI

2015-01-01

The opening of the mouse vaginal cavity to the skin is a postnatal tissue remodeling process that occurs at approximately five weeks of age for the completion of female genital tract maturation at puberty. The tissue remodeling process is primarily composed of a hormonally triggered apoptotic process predominantly occurring in the epithelium of the distal section of the vaginal cavity. However, the detailed mechanism underlying the apoptotic induction remains to be elucidated. In the present study, it was observed that the majority of BALB/c mice lacking the class 4 semaphorin, semaphorin 4D (Sema4D), developed imperforate vagina and hydrometrocolpos resulting in a perpetually unopened vaginal cavity regardless of a normal estrogen level comparable with that in wild-type (WT) mice. Administration of β-estradiol to infant Sema4D-deficient (Sema4D−/−) mice did not induce precocious vaginal opening, which was observed in WT mice subjected to the same β-estradiol administration, excluding the possibility that the closed vaginal phenotype was due to insufficient estrogen secretion at the time of vaginal opening. In order to assess the role of Sema4D in the postnatal vaginal tissue remodeling process, the expression of Sema4D and its receptor, plexin-B1, was examined as well as the level of apoptosis in the vaginal epithelia of five-week-old WT and Sema4D−/− mice. Immunohistochemical analyses confirmed the localization of Sema4D and plexin-B1 in the mouse vaginal epithelia. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and immunohistochemistry detecting activated caspase-3 revealed significantly fewer apoptotic cells in situ in the vaginal mucosa of five-week-old Sema4D−/− mice compared with WT mice. The addition of recombinant Sema4D to Sema4D−/− vaginal epithelial cells in culture significantly enhanced apoptosis of the vaginal epithelial cells, demonstrating the apoptosis-inducing activity of Sema4D. The experimental reduction of

Endothelial Semaphorin 7A promotes inflammation in seawater aspiration-induced acute lung injury.

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Zhang, Minlong; Wang, Li; Dong, Mingqing; Li, Zhichao; Jin, Faguang

2014-10-28

Inflammation is involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have shown that Semaphorin 7A (SEMA7A) promotes inflammation, there are limited reports regarding immunological function of SEMA7A in seawater aspiration-induced ALI. Therefore, we investigated the role of SEMA7A during seawater aspiration-induced ALI. Male Sprague-Dawley rats were underwent seawater instillation. Then, lung samples were collected at an indicated time for analysis. In addition, rat pulmonary microvascular endothelial cells (RPMVECs) were cultured and then stimulated with 25% seawater for indicated time point. After these treatments, cells samples were collected for analysis. In vivo, seawater instillation induced lung histopathologic changes, pro-inflammation cytokines release and increased expression of SEMA7A. In vitro, seawater stimulation led to pro-inflammation cytokine release, cytoskeleton remodeling and increased monolayer permeability in pulmonary microvascular endothelial cells. In addition, knockdown of hypoxia-inducible factor (HIF)-1α inhibited the seawater induced increase expression of SEMA7A. Meanwhile, knockdown of SEMA7A by specific siRNA inhibited the seawater induced aberrant inflammation, endothelial cytoskeleton remodeling and endothelial permeability. These results suggest that SEMA7A is critical in the development of lung inflammation and pulmonary edema in seawater aspiration-induced ALI, and may be a therapeutic target for this disease.

Grb2 mediates semaphorin-4D-dependent RhoA inactivation.

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Sun, Tianliang; Krishnan, Rameshkumar; Swiercz, Jakub M

2012-08-01

Signaling through the semaphorin 4D (Sema4D) receptor plexin-B1 is modulated by its interaction with tyrosine kinases ErbB-2 and Met. In cells expressing the plexin-B1-ErbB-2 receptor complex, ligand stimulation results in the activation of small GTPase RhoA and stimulation of cellular migration. By contrast, in cells expressing plexin-B1 and Met, ligand stimulation results in an association with the RhoGTPase-activating protein p190 RhoGAP and subsequent RhoA inactivation--a process that involves the tyrosine phosphorylation of plexin-B1 by Met. Inactivation of RhoA is necessary for Sema4D-mediated inhibition of cellular migration. It is, however, unknown how plexin-B1 phosphorylation regulates RhoGAP interaction and activity. Here we show that the activation of plexin-B1 by Sema4D and its subsequent tyrosine phosphorylation by Met creates a docking site for the SH2 domain of growth factor receptor bound-2 (Grb2). Grb2 is thereby recruited into the plexin-B1 receptor complex and, through its SH3 domain, interacts with p190 RhoGAP and mediates RhoA deactivation. Phosphorylation of plexin-B1 by Met and the recruitment of Grb2 have no effect on the R-RasGAP activity of plexin-B1, but are required for Sema4D-induced, RhoA-dependent antimigratory effects of Sema4D on breast cancer cells. These data show Grb2 as a direct link between plexin and p190-RhoGAP-mediated downstream signaling.

Acquisition and Neural Network Prediction of 3D Deformable Object Shape Using a Kinect and a Force-Torque Sensor.

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Tawbe, Bilal; Cretu, Ana-Maria

2017-05-11

The realistic representation of deformations is still an active area of research, especially for deformable objects whose behavior cannot be simply described in terms of elasticity parameters. This paper proposes a data-driven neural-network-based approach for capturing implicitly and predicting the deformations of an object subject to external forces. Visual data, in the form of 3D point clouds gathered by a Kinect sensor, is collected over an object while forces are exerted by means of the probing tip of a force-torque sensor. A novel approach based on neural gas fitting is proposed to describe the particularities of a deformation over the selectively simplified 3D surface of the object, without requiring knowledge of the object material. An alignment procedure, a distance-based clustering, and inspiration from stratified sampling support this process. The resulting representation is denser in the region of the deformation (an average of 96.6% perceptual similarity with the collected data in the deformed area), while still preserving the object's overall shape (86% similarity over the entire surface) and only using on average of 40% of the number of vertices in the mesh. A series of feedforward neural networks is then trained to predict the mapping between the force parameters characterizing the interaction with the object and the change in the object shape, as captured by the fitted neural gas nodes. This series of networks allows for the prediction of the deformation of an object when subject to unknown interactions.

Orientation of a 3D object: implementation with an artificial neural network using a programmable logic device

International Nuclear Information System (INIS)

Carnevale, Federico J.

2010-01-01

Complex information extraction from images is a key skill of intelligent machines, with wide application in automated systems, robotic manipulation and human-computer interaction. However, solving this problem with traditional, geometric or analytical, strategies is extremely difficult. Therefore, an approach based on learning from examples seems to be more appropriate. This thesis addresses the problem of 3D orientation, aiming to estimate the angular coordinates of a known object from an image shot from any direction. We describe a system based on artificial neural networks to solve this problem in real time. The implementation is performed using a programmable logic device. The digital system described in this paper has the ability to estimate two rotational coordinates of a 3D known object, in ranges from -80 0 to 80 0 . The operation speed allows a real time performance at video rate. The system accuracy can be successively increased by increasing the size of the artificial neural network and using a larger number of training examples [es

Genetic deletion of Rnd3 in neural stem cells promotes proliferation via upregulation of Notch signaling.

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Dong, Huimin; Lin, Xi; Li, Yuntao; Hu, Ronghua; Xu, Yang; Guo, Xiaojie; La, Qiong; Wang, Shun; Fang, Congcong; Guo, Junli; Li, Qi; Mao, Shanping; Liu, Baohui

2017-10-31

Rnd3, a Rho GTPase, is involved in the inhibition of actin cytoskeleton dynamics through the Rho kinase-dependent signaling pathway. We previously demonstrated that mice with genetic deletion of Rnd3 developed a markedly larger brain compared with wild-type mice. Here, we demonstrate that Rnd3 knockout mice developed an enlarged subventricular zone, and we identify a novel role for Rnd3 as an inhibitor of Notch signaling in neural stem cells. Rnd3 deficiency, both in vivo and in vitro , resulted in increased levels of Notch intracellular domain protein. This led to enhanced Notch signaling and promotion of aberrant neural stem cell growth, thereby resulting in a larger subventricular zone and a markedly larger brain. Inhibition of Notch activity abrogated this aberrant neural stem cell growth.

The murine homeobox gene Msx-3 shows highly restricted expression in the developing neural tube.

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Shimeld, S M; McKay, I J; Sharpe, P T

1996-04-01

The mouse homeobox-genes Msx-1 and Msx-2 are expressed in several areas of the developing embryo, including the neural tube, neural crest, facial processes and limb buds. Here we report the characterisation of a third mouse Msx gene, which we designate Msx-3. The embryonic expression of Msx-3 was found to differ from that of Msx-1 and -2 in that it was confined to the dorsal neural tube. In embryos with 5-8 somites a segmental pattern of expression was observed in the hindbrain, with rhombomeres 3 and 5 lacking Msx-3 while other rhombomeres expressed Msx-3. This pattern was transient, however, such that in embryos with 18 or more somites expression was continuous throughout the dorsal hindbrain and anterior dorsal spinal cord. Differentiation of dorsal cell types in the neural tube can be induced by addition of members of the Tgf-beta family. Additionally, Msx-1 and -2 have been shown to be activated by addition of the Tgf-beta family member Bmp-4. To determine if Bmp-4 could activate Msx-3, we incubated embryonic hindbrain explants with exogenous Bmp-4. The dorsal expression of Msx-3 was seen to expand into more ventral regions of the neurectoderm in Bmp-4-treated cultures, implying that Bmp-4 may be able to mimic an in vivo signal that induces Msx-3.

Novel Adaptive Forward Neural MIMO NARX Model for the Identification of Industrial 3-DOF Robot Arm Kinematics

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Ho Pham Huy Anh

2012-10-01

Full Text Available In this paper, a novel forward adaptive neural MIMO NARX model is used for modelling and identifying the forward kinematics of an industrial 3-DOF robot arm system. The nonlinear features of the forward kinematics of the industrial robot arm drive are thoroughly modelled based on the forward adaptive neural NARX model-based identification process using experimental input-output training data. This paper proposes a novel use of a back propagation (BP algorithm to generate the forward neural MIMO NARX (FNMN model for the forward kinematics of the industrial 3-DOF robot arm. The results show that the proposed adaptive neural NARX model trained by a Back Propagation learning algorithm yields outstanding performance and perfect accuracy.

Characterization of Pax3 and Sox10 transgenic Xenopus laevis embryos as tools to study neural crest development.

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Alkobtawi, Mansour; Ray, Heather; Barriga, Elias H; Moreno, Mauricio; Kerney, Ryan; Monsoro-Burq, Anne-Helene; Saint-Jeannet, Jean-Pierre; Mayor, Roberto

2018-03-06

The neural crest is a multipotent population of cells that originates a variety of cell types. Many animal models are used to study neural crest induction, migration and differentiation, with amphibians and birds being the most widely used systems. A major technological advance to study neural crest development in mouse, chick and zebrafish has been the generation of transgenic animals in which neural crest specific enhancers/promoters drive the expression of either fluorescent proteins for use as lineage tracers, or modified genes for use in functional studies. Unfortunately, no such transgenic animals currently exist for the amphibians Xenopus laevis and tropicalis, key model systems for studying neural crest development. Here we describe the generation and characterization of two transgenic Xenopus laevis lines, Pax3-GFP and Sox10-GFP, in which GFP is expressed in the pre-migratory and migratory neural crest, respectively. We show that Pax3-GFP could be a powerful tool to study neural crest induction, whereas Sox10-GFP could be used in the study of neural crest migration in living embryos. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Cell reprogramming by 3D bioprinting of human fibroblasts in polyurethane hydrogel for fabrication of neural-like constructs.

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Ho, Lin; Hsu, Shan-Hui

2018-04-01

3D bioprinting is a technique which enables the direct printing of biodegradable materials with cells into 3D tissue. So far there is no cell reprogramming in situ performed with the 3D bioprinting process. Forkhead box D3 (FoxD3) is a transcription factor and neural crest marker, which was reported to reprogram human fibroblasts into neural crest stem-like cells. In this study, we synthesized a new biodegradable thermo-responsive waterborne polyurethane (PU) gel as a bioink. FoxD3 plasmids and human fibroblasts were co-extruded with the PU hydrogel through the syringe needle tip for cell reprogramming. The rheological properties of the PU hydrogel including the modulus, gelation time, and shear thinning were optimized for the transfection effect of FoxD3 in situ. The corresponding shear rate and shear stress were examined. Results showed that human fibroblasts could be reprogrammed into neural crest stem-like cells with high cell viability during the extrusion process under an average shear stress ∼190 Pa. We further translated the method to the extrusion-based 3D bioprinting, and demonstrated that human fibroblasts co-printed with FoxD3 in the thermo-responsive PU hydrogel could be reprogrammed and differentiated into a neural-tissue like construct at 14 days after induction. The neural-like tissue construct produced by 3D bioprinting from human fibroblasts may be applied to personalized drug screening or neuroregeneration. There is no study so far on cell reprogramming in situ with 3D bioprinting. In this manuscript, a new thermoresponsive polyurethane bioink was developed and employed to deliver FoxD3 plasmid into human fibroblasts by the extrusion-based bioprinting. When the polyurethane gel was extruded through the syringe tip, the shear stress generated may have caused the transient membrane permeability for transfection. The shear stress was optimized for transfection in situ by 3D bioprinting. We demonstrated that human fibroblasts could be

In Vitro Studies on a Microfluidic Sensor with Embedded Obstacles Using New Antibacterial Synthetic Compounds (1-TDPPO Mixed Prop-2-en-1-one with Difluoro Phenyl

Directory of Open Access Journals (Sweden)

Changhyun Roh

2017-04-01

Full Text Available This paper describes the use of an analytical microfluidic sensor for accelerating chemo-repellent response and strong anti-bacterial 1-(Thien-2-yl-3-(2, 6-difluoro phenyl prop-2-en-1-one (1-TDPPO. The chemically-synthesized antimicrobial agent, which included prop-2-en-1-one and difluoro phenyl groups, was moving through an optically transparent polydimethylsiloxane (PDMS microfluidic sensor with circular obstacles arranged evenly. The response, growth and distribution of fluorescent labeling Pseudomonas aeruginosa PAO1 against the antimicrobial agent were monitored by confocal laser scanning microscope (CLSM. The microfluidic sensor along with 1-TDPPOin this study exhibits the following advantages: (i Real-time chemo-repellent responses of cell dynamics; (ii Rapid eradication of biofilm by embedded obstacles and powerful antibacterial agents, which significantly reduce the response time compared to classical methods; (iii Minimal consumption of cells and antimicrobial agents; and (iv Simplifying the process of the normalization of the fluorescence intensity and monitoring of biofilm by captured images and datasets.

Neural cell 3D microtissue formation is marked by cytokines' up-regulation.

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Yinzhi Lai

Full Text Available Cells cultured in three dimensional (3D scaffolds as opposed to traditional two-dimensional (2D substrates have been considered more physiologically relevant based on their superior ability to emulate the in vivo environment. Combined with stem cell technology, 3D cell cultures can provide a promising alternative for use in cell-based assays or biosensors in non-clinical drug discovery studies. To advance 3D culture technology, a case has been made for identifying and validating three-dimensionality biomarkers. With this goal in mind, we conducted a transcriptomic expression comparison among neural progenitor cells cultured on 2D substrates, 3D porous polystyrene scaffolds, and as 3D neurospheres (in vivo surrogate. Up-regulation of cytokines as a group in 3D and neurospheres was observed. A group of 13 cytokines were commonly up-regulated in cells cultured in polystyrene scaffolds and neurospheres, suggesting potential for any or a combination from this list to serve as three-dimensionality biomarkers. These results are supportive of further cytokine identification and validation studies with cells from non-neural tissue.

Effects of mechanical repetitive load on bone quality around implants in rat maxillae.

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Yusuke Uto

Full Text Available Greater understanding and acceptance of the new concept "bone quality", which was proposed by the National Institutes of Health and is based on bone cells and collagen fibers, are required. The novel protein Semaphorin3A (Sema3A is associated with osteoprotection by regulating bone cells. The aims of this study were to investigate the effects of mechanical loads on Sema3A production and bone quality based on bone cells and collagen fibers around implants in rat maxillae. Grade IV-titanium threaded implants were placed at 4 weeks post-extraction in maxillary first molars. Implants received mechanical loads (10 N, 3 Hz for 1800 cycles, 2 days/week for 5 weeks from 3 weeks post-implant placement to minimize the effects of wound healing processes by implant placement. Bone structures, bone mineral density (BMD, Sema3A production and bone quality based on bone cells and collagen fibers were analyzed using microcomputed tomography, histomorphometry, immunohistomorphometry, polarized light microscopy and birefringence measurement system inside of the first and second thread (designated as thread A and B, respectively, as mechanical stresses are concentrated and differently distributed on the first two threads from the implant neck. Mechanical load significantly increased BMD, but not bone volume around implants. Inside thread B, but not thread A, mechanical load significantly accelerated Sema3A production with increased number of osteoblasts and osteocytes, and enhanced production of both type I and III collagen. Moreover, mechanical load also significantly induced preferential alignment of collagen fibers in the lower flank of thread B. These data demonstrate that mechanical load has different effects on Sema3A production and bone quality based on bone cells and collagen fibers between the inside threads of A and B. Mechanical load-induced Sema3A production may be differentially regulated by the type of bone structure or distinct stress distribution

An Autocrine Proliferation Repressor Regulates Dictyostelium discoideum Proliferation and Chemorepulsion Using the G Protein-Coupled Receptor GrlH

OpenAIRE

Yu Tang; Yuantai Wu; Sarah E. Herlihy; Francisco J. Brito-Aleman; Jose H. Ting; Chris Janetopoulos; Richard H. Gomer; Scott D. Emr

2018-01-01

In eukaryotic microbes, little is known about signals that inhibit the proliferation of the cells that secrete the signal, and little is known about signals (chemorepellents) that cause cells to move away from the source of the signal. Autocrine proliferation repressor protein A (AprA) is a protein secreted by the eukaryotic microbe Dictyostelium discoideum. AprA is a chemorepellent for and inhibits the proliferation of D. discoideum. We previously found that cells sense AprA using G proteins...

Imaging of human differentiated 3D neural aggregates using light sheet fluorescence microscopy

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Gualda, Emilio J.; Simão, Daniel; Pinto, Catarina; Alves, Paula M.; Brito, Catarina

2014-01-01

The development of three dimensional (3D) cell cultures represents a big step for the better understanding of cell behavior and disease in a more natural like environment, providing not only single but multiple cell type interactions in a complex 3D matrix, highly resembling physiological conditions. Light sheet fluorescence microscopy (LSFM) is becoming an excellent tool for fast imaging of such 3D biological structures. We demonstrate the potential of this technique for the imaging of human differentiated 3D neural aggregates in fixed and live samples, namely calcium imaging and cell death processes, showing the power of imaging modality compared with traditional microscopy. The combination of light sheet microscopy and 3D neural cultures will open the door to more challenging experiments involving drug testing at large scale as well as a better understanding of relevant biological processes in a more realistic environment. PMID:25161607

Travelling plateaus for a hyperbolic Keller–Segel system with attraction and repulsion: existence and branching instabilities

International Nuclear Information System (INIS)

Perthame, Benoît; Tang, Min; Vauchelet, Nicolas; Schmeiser, Christian

2011-01-01

How can repulsive and attractive forces, acting on a conservative system, create stable travelling patterns or branching instabilities? We have proposed to study this question in the framework of the hyperbolic Keller–Segel system with logistic sensitivity. This is a model system motivated by experiments on cell communities auto-organization, a field which is also called socio-biology. We continue earlier modelling work, where we have shown numerically that branching patterns arise for this system and we have analysed this instability by formal asymptotics for small diffusivity of the chemo-repellent. Here we are interested in the more general situation, where the diffusivities of both the chemo-attractant and the chemo-repellent are positive. To do so, we develop an appropriate functional analysis framework. We apply our method to two cases. Firstly we analyse steady states. Secondly we analyse travelling waves when neglecting the degradation coefficient of the chemo-repellent; the unique wave speed appears through a singularity cancellation which is the main theoretical difficulty. This shows that in different situations the cell density takes the shape of a plateau. The existence of steady states and travelling plateaus are a symptom of how rich the system is and why branching instabilities can occur. Numerical tests show that large plateaus may split into smaller ones, which remain stable

3D position estimation using an artificial neural network for a continuous scintillator PET detector

International Nuclear Information System (INIS)

Wang, Y; Zhu, W; Cheng, X; Li, D

2013-01-01

Continuous crystal based PET detectors have features of simple design, low cost, good energy resolution and high detection efficiency. Through single-end readout of scintillation light, direct three-dimensional (3D) position estimation could be another advantage that the continuous crystal detector would have. In this paper, we propose to use artificial neural networks to simultaneously estimate the plane coordinate and DOI coordinate of incident γ photons with detected scintillation light. Using our experimental setup with an ‘8 + 8’ simplified signal readout scheme, the training data of perpendicular irradiation on the front surface and one side surface are obtained, and the plane (x, y) networks and DOI networks are trained and evaluated. The test results show that the artificial neural network for DOI estimation is as effective as for plane estimation. The performance of both estimators is presented by resolution and bias. Without bias correction, the resolution of the plane estimator is on average better than 2 mm and that of the DOI estimator is about 2 mm over the whole area of the detector. With bias correction, the resolution at the edge area for plane estimation or at the end of the block away from the readout PMT for DOI estimation becomes worse, as we expect. The comprehensive performance of the 3D positioning by a neural network is accessed by the experimental test data of oblique irradiations. To show the combined effect of the 3D positioning over the whole area of the detector, the 2D flood images of oblique irradiation are presented with and without bias correction. (paper)

Histamine H3 receptor density is negatively correlated with neural activity related to working memory in humans.

Science.gov (United States)

Ito, Takehito; Kimura, Yasuyuki; Seki, Chie; Ichise, Masanori; Yokokawa, Keita; Kawamura, Kazunori; Takahashi, Hidehiko; Higuchi, Makoto; Zhang, Ming-Rong; Suhara, Tetsuya; Yamada, Makiko

2018-06-14

The histamine H 3 receptor is regarded as a drug target for cognitive impairments in psychiatric disorders. H 3 receptors are expressed in neocortical areas, including the prefrontal cortex, the key region of cognitive functions such as working memory. However, the role of prefrontal H 3 receptors in working memory has not yet been clarified. Therefore, using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) techniques, we aimed to investigate the association between the neural activity of working memory and the density of H 3 receptors in the prefrontal cortex. Ten healthy volunteers underwent both fMRI and PET scans. The N-back task was used to assess the neural activities related to working memory. H 3 receptor density was measured with the selective PET radioligand [ 11 C] TASP457. The neural activity of the right dorsolateral prefrontal cortex during the performance of the N-back task was negatively correlated with the density of H 3 receptors in this region. Higher neural activity of working memory was associated with lower H 3 receptor density in the right dorsolateral prefrontal cortex. This finding elucidates the role of H 3 receptors in working memory and indicates the potential of H 3 receptors as a therapeutic target for the cognitive impairments associated with neuropsychiatric disorders.

Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects.

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Bauters, Marijke; Frints, Suzanna G; Van Esch, Hilde; Spruijt, Liesbeth; Baldewijns, Marcella M; de Die-Smulders, Christine E M; Fryns, Jean-Pierre; Marynen, Peter; Froyen, Guy

2014-08-01

Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from 138.7 to 139.8 Mb, harboring only two annotated genes, SOX3 and ATP11C, and was shown to be a direct tandem copy number gain. Unexpectedly, the microduplication did not fully segregate with the disease in this family suggesting that SOX3 duplications have variable penetrance for X-linked hypopituitarism. In the same family, a female fetus presenting with a neural tube defect was also shown to carry the SOX3 copy number gain. Since we also demonstrated increased SOX3 mRNA levels in amnion cells derived from an unrelated t(X;22)(q27;q11) female fetus with spina bifida, we propose that increased levels of SOX3 could be a risk factor for neural tube defects. © 2014 Wiley Periodicals, Inc.

Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

International Nuclear Information System (INIS)

Manceur, Aziza P.; Tseng, Michael; Holowacz, Tamara; Witterick, Ian; Weksberg, Rosanna; McCurdy, Richard D.; Warsh, Jerry J.; Audet, Julie

2011-01-01

The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

A key role for poly(ADP-ribose polymerase 3 in ectodermal specification and neural crest development.

Directory of Open Access Journals (Sweden)

Michèle Rouleau

2011-01-01

Full Text Available The PARP family member poly(ADP-ribose polymerase 3 (PARP3 is structurally related to the well characterized PARP1 that orchestrates cellular responses to DNA strand breaks and cell death by the synthesis of poly(ADP-ribose. In contrast to PARP1 and PARP2, the functions of PARP3 are undefined. Here, we reveal critical functions for PARP3 during vertebrate development.We have used several in vitro and in vivo approaches to examine the possible functions of PARP3 as a transcriptional regulator, a function suggested from its previously reported association with several Polycomb group (PcG proteins. We demonstrate that PARP3 gene occupancy in the human neuroblastoma cell line SK-N-SH occurs preferentially with developmental genes regulating cell fate specification, tissue patterning, craniofacial development and neurogenesis. Addressing the significance of this association during zebrafish development, we show that morpholino oligonucleotide-directed inhibition of parp3 expression in zebrafish impairs the expression of the neural crest cell specifier sox9a and of dlx3b/dlx4b, the formation of cranial sensory placodes, inner ears and pectoral fins. It delays pigmentation and severely impedes the development of the median fin fold and tail bud.Our findings demonstrate that Parp3 is crucial in the early stages of zebrafish development, possibly by exerting its transcriptional regulatory functions as early as during the specification of the neural plate border.

3D multi-view convolutional neural networks for lung nodule classification

Science.gov (United States)

Kang, Guixia; Hou, Beibei; Zhang, Ningbo

2017-01-01

The 3D convolutional neural network (CNN) is able to make full use of the spatial 3D context information of lung nodules, and the multi-view strategy has been shown to be useful for improving the performance of 2D CNN in classifying lung nodules. In this paper, we explore the classification of lung nodules using the 3D multi-view convolutional neural networks (MV-CNN) with both chain architecture and directed acyclic graph architecture, including 3D Inception and 3D Inception-ResNet. All networks employ the multi-view-one-network strategy. We conduct a binary classification (benign and malignant) and a ternary classification (benign, primary malignant and metastatic malignant) on Computed Tomography (CT) images from Lung Image Database Consortium and Image Database Resource Initiative database (LIDC-IDRI). All results are obtained via 10-fold cross validation. As regards the MV-CNN with chain architecture, results show that the performance of 3D MV-CNN surpasses that of 2D MV-CNN by a significant margin. Finally, a 3D Inception network achieved an error rate of 4.59% for the binary classification and 7.70% for the ternary classification, both of which represent superior results for the corresponding task. We compare the multi-view-one-network strategy with the one-view-one-network strategy. The results reveal that the multi-view-one-network strategy can achieve a lower error rate than the one-view-one-network strategy. PMID:29145492

Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

Energy Technology Data Exchange (ETDEWEB)

Manceur, Aziza P. [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Tseng, Michael [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Holowacz, Tamara [Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Witterick, Ian [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Department of Otolaryngology, Head and Neck Surgery, University of Toronto, ON (Canada); Weksberg, Rosanna [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); McCurdy, Richard D. [The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); Warsh, Jerry J. [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Audet, Julie, E-mail: julie.audet@utoronto.ca [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada)

2011-09-10

The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

Neural patterning of human induced pluripotent stem cells in 3-D cultures for studying biomolecule-directed differential cellular responses.

Science.gov (United States)

Yan, Yuanwei; Bejoy, Julie; Xia, Junfei; Guan, Jingjiao; Zhou, Yi; Li, Yan

2016-09-15

Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells/tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capacity of signaling factors that regulate 3-D neural tissue patterning in vitro and differential responses of the resulting neural populations to various biomolecules have not yet been fully understood. By tuning neural patterning of hiPSCs with small molecules targeting sonic hedgehog (SHH) signaling, this study generated different 3-D neuronal cultures that were mainly comprised of either cortical glutamatergic neurons or motor neurons. Abundant glutamatergic neurons were observed following the treatment with an antagonist of SHH signaling, cyclopamine, while Islet-1 and HB9-expressing motor neurons were enriched by an SHH agonist, purmorphamine. In neurons derived with different neural patterning factors, whole-cell patch clamp recordings showed similar voltage-gated Na(+)/K(+) currents, depolarization-evoked action potentials and spontaneous excitatory post-synaptic currents. Moreover, these different neuronal populations exhibited differential responses to three classes of biomolecules, including (1) matrix metalloproteinase inhibitors that affect extracellular matrix remodeling; (2) N-methyl-d-aspartate that induces general neurotoxicity; and (3) amyloid β (1-42) oligomers that cause neuronal subtype-specific neurotoxicity. This study should advance our understanding of hiPSC self-organization and neural tissue development and provide a transformative approach to establish 3-D models for neurological disease modeling and drug discovery. Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells, tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capability of sonic hedgehog-related small molecules to tune

2D neural hardware versus 3D biological ones

Energy Technology Data Exchange (ETDEWEB)

Beiu, V.

1998-12-31

This paper will present important limitations of hardware neural nets as opposed to biological neural nets (i.e. the real ones). The author starts by discussing neural structures and their biological inspirations, while mentioning the simplifications leading to artificial neural nets. Going further, the focus will be on hardware constraints. The author will present recent results for three different alternatives of implementing neural networks: digital, threshold gate, and analog, while the area and the delay will be related to neurons' fan-in and weights' precision. Based on all of these, it will be shown why hardware implementations cannot cope with their biological inspiration with respect to their power of computation: the mapping onto silicon lacking the third dimension of biological nets. This translates into reduced fan-in, and leads to reduced precision. The main conclusion is that one is faced with the following alternatives: (1) try to cope with the limitations imposed by silicon, by speeding up the computation of the elementary silicon neurons; (2) investigate solutions which would allow one to use the third dimension, e.g. using optical interconnections.

Novel Adaptive Forward Neural MIMO NARX Model for the Identification of Industrial 3-DOF Robot Arm Kinematics

OpenAIRE

Ho Pham Huy Anh; Nguyen Thanh Nam

2012-01-01

In this paper, a novel forward adaptive neural MIMO NARX model is used for modelling and identifying the forward kinematics of an industrial 3‐DOF robot arm system. The nonlinear features of the forward kinematics of the industrial robot arm drive are thoroughly modelled based on the forward adaptive neural NARX model‐based identification process using experimental input‐output training data. This paper proposes a novel use of a back propagation (BP) algorithm to generate the forward neural M...

Identification of Noncanonical Wnt Receptors Required for Wnt-3a-Induced Early Differentiation of Human Neural Stem Cells.

Science.gov (United States)

Bengoa-Vergniory, Nora; Gorroño-Etxebarria, Irantzu; López-Sánchez, Inmaculada; Marra, Michele; Di Chiaro, Pierluigi; Kypta, Robert

2017-10-01

Wnt proteins preferentially activate either β-catenin-dependent or β-catenin-independent signals, but the activity of a particular Wnt also depends on cellular context and receptor availability. We previously reported that Wnt-3a induces neural differentiation of human embryonic stem cell-derived neural stem cells (NSCs) in a β-catenin-independent manner by activating a signal involving JNK and the AP-1 family member ATF-2. Here, we report the results of a gene silencing approach to identify the Wnt receptors that mediate this response to Wnt-3a. Silencing of ROR2 increased neuronal differentiation, as measured by expression of the genes DCX, NEUROD1, and NGN1, suggesting ROR2 signals normally prevent differentiation. Silencing of the other Wnt receptors singly did not affect Wnt-3a-induced neuronal differentiation. However, pairwise silencing of ROR1 and FZD4 or FZD5 and of LRP6 and FZD4 or FZD5 inhibited neuronal differentiation, as detected by reductions in the expression of neuronal genes and immunocytochemical detection of DCX, NEUROD1 and DCX. Ectopic expression of these receptors in HEK 293 cells increased ATF2-dependent transcription. In addition, ROR1 coimmunoprecipitated with FZD4 and LRP6 in transfected HEK 293 cells and colocalized with FZD4 and with LRP6 at the cell surface of transfected L cells. Wnt-3a did not appear to affect these interactions but did alter the interactions between LRP6 and FZD4/5. Together, these observations highlight roles for ROR1, LRP6, FZD4, and FZD5 in neural stem cell differentiation and provide support for a model in which dynamic interactions among these receptors mediate Wnt-3a activation of ATF2 signaling.

GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

International Nuclear Information System (INIS)

Boku, Shuken; Nakagawa, Shin; Takamura, Naoki; Kato, Akiko; Takebayashi, Minoru; Hisaoka-Nakashima, Kazue; Omiya, Yuki; Inoue, Takeshi; Kusumi, Ichiro

2013-01-01

Highlights: •GDNF has no effect on ADP proliferation and apoptosis. •GDNF increases ADP differentiation into astrocyte. •A specific inhibitor of STAT3 decreases the astrogliogenic effect of GDNF. •STAT3 knockdown by lentiviral shRNA vector also decreases the astrogliogenic effect of GDNF. •GDNF increases the phosphorylation of STAT3. -- Abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis

GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

Energy Technology Data Exchange (ETDEWEB)

Boku, Shuken, E-mail: shuboku@med.hokudai.ac.jp [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Nakagawa, Shin [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Takamura, Naoki [Pharmaceutical Laboratories, Dainippon Sumitomo Pharma Co. Ltd., Osaka (Japan); Kato, Akiko [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Takebayashi, Minoru [Department of Psychiatry, National Hospital Organization Kure Medical Center, Kure (Japan); Hisaoka-Nakashima, Kazue [Department of Pharmacology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima (Japan); Omiya, Yuki; Inoue, Takeshi; Kusumi, Ichiro [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan)

2013-05-17

Highlights: •GDNF has no effect on ADP proliferation and apoptosis. •GDNF increases ADP differentiation into astrocyte. •A specific inhibitor of STAT3 decreases the astrogliogenic effect of GDNF. •STAT3 knockdown by lentiviral shRNA vector also decreases the astrogliogenic effect of GDNF. •GDNF increases the phosphorylation of STAT3. -- Abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis.

Expression of p53/HGF/c-met/STAT3 signal in fetuses with neural tube defects.

Science.gov (United States)

Trovato, Maria; D'Armiento, Maria; Lavra, Luca; Ulivieri, Alessandra; Dominici, Roberto; Vitarelli, Enrica; Grosso, Maddalena; Vecchione, Raffaella; Barresi, Gaetano; Sciacchitano, Salvatore

2007-02-01

Neural tube defects (NTD) are morphogenetic alterations due to a defective closure of neural tube. Hepatocyte growth factor (HGF)/c-met system plays a role in morphogenesis of nervous system, lung, and kidney. HGF/c-met morphogenetic effects are mediated by signal transducers and activators of transcription (STAT)3 and both HGF and c-met genes are regulated from p53. The aim of our study was to analyze mRNA and protein expressions of p53, HGF, c-met, and STAT3 in fetuses with NTD. By reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analyzed neural tissues from four NTD fetuses and the corresponding non-malformed lungs, kidneys and placentas. We found a reduced mRNA expression of HGF/c-met/STAT3 pathway, in the malformed nervous systems and placentas. The reduced expression of this pathway correlated with the absence of p53 in all these samples. On the contrary, detectable expression levels of p53, HGF, c-met, and STAT3 were observed in non-malformed lungs and kidneys obtained from the same fetuses. Comparable results were obtained by immunohistochemistry, with the exception of p53, which was undetected in all fetal tissues. In conclusion, in NTD fetuses, both the defective neural tube tissue and the placenta have a reduction in all components of the p53/HGF/c-met/STAT3 cascade. This raises the possibility of using the suppression of these genes for early diagnosis of NTD especially on chorionic villus sampling.

A Wireless and Batteryless Microsystem with Implantable Grid Electrode/3-Dimensional Probe Array for ECoG and Extracellular Neural Recording in Rats

Directory of Open Access Journals (Sweden)

Chih-Wei Chang

2013-04-01

Full Text Available This paper presents the design and implementation of an integrated wireless microsystem platform that provides the possibility to support versatile implantable neural sensing devices in free laboratory rats. Inductive coupled coils with low dropout regulator design allows true long-term recording without limitation of battery capacity. A 16-channel analog front end chip located on the headstage is designed for high channel account neural signal conditioning with low current consumption and noise. Two types of implantable electrodes including grid electrode and 3D probe array are also presented for brain surface recording and 3D biopotential acquisition in the implanted target volume of tissue. The overall system consumes less than 20 mA with small form factor, 3.9 × 3.9 cm2 mainboard and 1.8 × 3.4 cm2 headstage, is packaged into a backpack for rats. Practical in vivo recordings including auditory response, brain resection tissue and PZT-induced seizures recording demonstrate the correct function of the proposed microsystem. Presented achievements addressed the aforementioned properties by combining MEMS neural sensors, low-power circuit designs and commercial chips into system-level integration.

Computational optical tomography using 3-D deep convolutional neural networks

Science.gov (United States)

Nguyen, Thanh; Bui, Vy; Nehmetallah, George

2018-04-01

Deep convolutional neural networks (DCNNs) offer a promising performance for many image processing areas, such as super-resolution, deconvolution, image classification, denoising, and segmentation, with outstanding results. Here, we develop for the first time, to our knowledge, a method to perform 3-D computational optical tomography using 3-D DCNN. A simulated 3-D phantom dataset was first constructed and converted to a dataset of phase objects imaged on a spatial light modulator. For each phase image in the dataset, the corresponding diffracted intensity image was experimentally recorded on a CCD. We then experimentally demonstrate the ability of the developed 3-D DCNN algorithm to solve the inverse problem by reconstructing the 3-D index of refraction distributions of test phantoms from the dataset from their corresponding diffraction patterns.

A neural flow estimator

DEFF Research Database (Denmark)

Jørgensen, Ivan Harald Holger; Bogason, Gudmundur; Bruun, Erik

1995-01-01

This paper proposes a new way to estimate the flow in a micromechanical flow channel. A neural network is used to estimate the delay of random temperature fluctuations induced in a fluid. The design and implementation of a hardware efficient neural flow estimator is described. The system...... is implemented using switched-current technique and is capable of estimating flow in the μl/s range. The neural estimator is built around a multiplierless neural network, containing 96 synaptic weights which are updated using the LMS1-algorithm. An experimental chip has been designed that operates at 5 V...

Neural Networks

International Nuclear Information System (INIS)

Smith, Patrick I.

2003-01-01

Physicists use large detectors to measure particles created in high-energy collisions at particle accelerators. These detectors typically produce signals indicating either where ionization occurs along the path of the particle, or where energy is deposited by the particle. The data produced by these signals is fed into pattern recognition programs to try to identify what particles were produced, and to measure the energy and direction of these particles. Ideally, there are many techniques used in this pattern recognition software. One technique, neural networks, is particularly suitable for identifying what type of particle caused by a set of energy deposits. Neural networks can derive meaning from complicated or imprecise data, extract patterns, and detect trends that are too complex to be noticed by either humans or other computer related processes. To assist in the advancement of this technology, Physicists use a tool kit to experiment with several neural network techniques. The goal of this research is interface a neural network tool kit into Java Analysis Studio (JAS3), an application that allows data to be analyzed from any experiment. As the final result, a physicist will have the ability to train, test, and implement a neural network with the desired output while using JAS3 to analyze the results or output. Before an implementation of a neural network can take place, a firm understanding of what a neural network is and how it works is beneficial. A neural network is an artificial representation of the human brain that tries to simulate the learning process [5]. It is also important to think of the word artificial in that definition as computer programs that use calculations during the learning process. In short, a neural network learns by representative examples. Perhaps the easiest way to describe the way neural networks learn is to explain how the human brain functions. The human brain contains billions of neural cells that are responsible for processing

NEURAL AND CARDIAC TOXICITIES ASSOCIATED WITH 3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA)

OpenAIRE

Baumann, Michael H.; Rothman, Richard B.

2009-01-01

(±)-3,4-Methylenedioxymethamphetamine (MDMA) is a commonly abused illicit drug which affects multiple organ systems. In animals, high-dose administration of MDMA produces deficits in serotonin (5-HT) neurons (e.g., depletion of forebrain 5-HT) that have been viewed as neurotoxicity. Recent data implicate MDMA in the development of valvular heart disease (VHD). The present paper reviews several issues related to MDMA-associated neural and cardiac toxicities. The hypothesis of MDMA neurotoxicit...

Imaging of human differentiated 3D neural aggregates using light sheet fluorescence microscopy

Directory of Open Access Journals (Sweden)

Emilio J Gualda

2014-08-01

Full Text Available The development of three dimensional cell cultures represents a big step for the better understanding of cell behavior and disease in a more natural like environment, providing not only single but multiple cell type interactions in a complex three dimensional matrix, highly resembling physiological conditions. Light sheet fluorescence microscopy is becoming an excellent tool for fast imaging of such three-dimensional biological structures. We demonstrate the potential of this technique for the imaging of human differentiated 3D neural aggregates in fixed and live samples, namely calcium imaging and cell death processes, showing the power of imaging modality compared with traditional microscopy. The combination of light sheet microscopy and 3D neural cultures will open the door to more challenging experiments involving drug testing at large scale as well as a better understanding of relevant biological processes in a more realistic environment.

Neural Parallel Engine: A toolbox for massively parallel neural signal processing.

Science.gov (United States)

Tam, Wing-Kin; Yang, Zhi

2018-05-01

Large-scale neural recordings provide detailed information on neuronal activities and can help elicit the underlying neural mechanisms of the brain. However, the computational burden is also formidable when we try to process the huge data stream generated by such recordings. In this study, we report the development of Neural Parallel Engine (NPE), a toolbox for massively parallel neural signal processing on graphical processing units (GPUs). It offers a selection of the most commonly used routines in neural signal processing such as spike detection and spike sorting, including advanced algorithms such as exponential-component-power-component (EC-PC) spike detection and binary pursuit spike sorting. We also propose a new method for detecting peaks in parallel through a parallel compact operation. Our toolbox is able to offer a 5× to 110× speedup compared with its CPU counterparts depending on the algorithms. A user-friendly MATLAB interface is provided to allow easy integration of the toolbox into existing workflows. Previous efforts on GPU neural signal processing only focus on a few rudimentary algorithms, are not well-optimized and often do not provide a user-friendly programming interface to fit into existing workflows. There is a strong need for a comprehensive toolbox for massively parallel neural signal processing. A new toolbox for massively parallel neural signal processing has been created. It can offer significant speedup in processing signals from large-scale recordings up to thousands of channels. Copyright © 2018 Elsevier B.V. All rights reserved.

Neurally and ocularly informed graph-based models for searching 3D environments

Science.gov (United States)

Jangraw, David C.; Wang, Jun; Lance, Brent J.; Chang, Shih-Fu; Sajda, Paul

2014-08-01

Objective. As we move through an environment, we are constantly making assessments, judgments and decisions about the things we encounter. Some are acted upon immediately, but many more become mental notes or fleeting impressions—our implicit ‘labeling’ of the world. In this paper, we use physiological correlates of this labeling to construct a hybrid brain-computer interface (hBCI) system for efficient navigation of a 3D environment. Approach. First, we record electroencephalographic (EEG), saccadic and pupillary data from subjects as they move through a small part of a 3D virtual city under free-viewing conditions. Using machine learning, we integrate the neural and ocular signals evoked by the objects they encounter to infer which ones are of subjective interest to them. These inferred labels are propagated through a large computer vision graph of objects in the city, using semi-supervised learning to identify other, unseen objects that are visually similar to the labeled ones. Finally, the system plots an efficient route to help the subjects visit the ‘similar’ objects it identifies. Main results. We show that by exploiting the subjects’ implicit labeling to find objects of interest instead of exploring naively, the median search precision is increased from 25% to 97%, and the median subject need only travel 40% of the distance to see 84% of the objects of interest. We also find that the neural and ocular signals contribute in a complementary fashion to the classifiers’ inference of subjects’ implicit labeling. Significance. In summary, we show that neural and ocular signals reflecting subjective assessment of objects in a 3D environment can be used to inform a graph-based learning model of that environment, resulting in an hBCI system that improves navigation and information delivery specific to the user’s interests.

Neurally and ocularly informed graph-based models for searching 3D environments.

Science.gov (United States)

Jangraw, David C; Wang, Jun; Lance, Brent J; Chang, Shih-Fu; Sajda, Paul

2014-08-01

As we move through an environment, we are constantly making assessments, judgments and decisions about the things we encounter. Some are acted upon immediately, but many more become mental notes or fleeting impressions-our implicit 'labeling' of the world. In this paper, we use physiological correlates of this labeling to construct a hybrid brain-computer interface (hBCI) system for efficient navigation of a 3D environment. First, we record electroencephalographic (EEG), saccadic and pupillary data from subjects as they move through a small part of a 3D virtual city under free-viewing conditions. Using machine learning, we integrate the neural and ocular signals evoked by the objects they encounter to infer which ones are of subjective interest to them. These inferred labels are propagated through a large computer vision graph of objects in the city, using semi-supervised learning to identify other, unseen objects that are visually similar to the labeled ones. Finally, the system plots an efficient route to help the subjects visit the 'similar' objects it identifies. We show that by exploiting the subjects' implicit labeling to find objects of interest instead of exploring naively, the median search precision is increased from 25% to 97%, and the median subject need only travel 40% of the distance to see 84% of the objects of interest. We also find that the neural and ocular signals contribute in a complementary fashion to the classifiers' inference of subjects' implicit labeling. In summary, we show that neural and ocular signals reflecting subjective assessment of objects in a 3D environment can be used to inform a graph-based learning model of that environment, resulting in an hBCI system that improves navigation and information delivery specific to the user's interests.

Effect of 3D-scaffold formation on differentiation and survival in human neural progenitor cells.

Science.gov (United States)

Ortinau, Stefanie; Schmich, Jürgen; Block, Stephan; Liedmann, Andrea; Jonas, Ludwig; Weiss, Dieter G; Helm, Christiane A; Rolfs, Arndt; Frech, Moritz J

2010-11-11

3D-scaffolds have been shown to direct cell growth and differentiation in many different cell types, with the formation and functionalisation of the 3D-microenviroment being important in determining the fate of the embedded cells. Here we used a hydrogel-based scaffold to investigate the influences of matrix concentration and functionalisation with laminin on the formation of the scaffolds, and the effect of these scaffolds on human neural progenitor cells cultured within them. In this study we used different concentrations of the hydrogel-based matrix PuraMatrix. In some experiments we functionalised the matrix with laminin I. The impact of concentration and treatment with laminin on the formation of the scaffold was examined with atomic force microscopy. Cells from a human fetal neural progenitor cell line were cultured in the different matrices, as well as in a 2D culture system, and were subsequently analysed with antibody stainings against neuronal markers. In parallel, the survival rate of the cells was determined by a live/dead assay. Atomic force microscopy measurements demonstrated that the matrices are formed by networks of isolated PuraMatrix fibres and aggregates of fibres. An increase of the hydrogel concentration led to a decrease in the mesh size of the scaffolds and functionalisation with laminin promoted aggregation of the fibres (bundle formation), which further reduces the density of isolated fibres. We showed that laminin-functionalisation is essential for human neural progenitor cells to build up 3D-growth patterns, and that proliferation of the cells is also affected by the concentration of matrix. In addition we found that 3D-cultures enhanced neuronal differentiation and the survival rate of the cells compared to 2D-cultures. Taken together, we have demonstrated a direct influence of the 3D-scaffold formation on the survival and neuronal differentiation of human neural progenitor cells. These findings emphasize the importance of optimizing 3

A spontaneous and novel Pax3 mutant mouse that models Waardenburg syndrome and neural tube defects.

Science.gov (United States)

Ohnishi, Tetsuo; Miura, Ikuo; Ohba, Hisako; Shimamoto, Chie; Iwayama, Yoshimi; Wakana, Shigeharu; Yoshikawa, Takeo

2017-04-05

Genes responsible for reduced pigmentation phenotypes in rodents are associated with human developmental defects, such as Waardenburg syndrome, where patients display congenital deafness along with various abnormalities mostly related to neural crest development deficiency. In this study, we identified a spontaneous mutant mouse line Rwa, which displays variable white spots on mouse bellies and white digits and tail, on a C57BL/6N genetic background. Curly tail and spina bifida were also observed, although at a lower penetrance. These phenotypes were dominantly inherited by offspring. We searched for the genetic mechanism of the observed phenotypes. We harnessed a rapid mouse gene mapping system newly developed in our laboratories to identify a responsible gene. We detected a region within chromosome 1 as a probable locus for the causal mutation. Dense mapping using interval markers narrowed the locus down to a 670-kbp region, containing four genes including Pax3, a gene known to be implicated in the types I and III Waardenburg syndrome. Extensive mutation screening of Pax3 detected an 841-bp deletion, spanning the promoter region and intron 1 of the gene. The defective allele of Pax3, named Pax3 Rwa , lacked the first coding exon and co-segregated perfectly with the phenotypes, confirming its causal nature. The genetic background of Rwa mice is almost identical to that of inbred C57BL/6N. These results highlight Pax3 Rwa mice as a beneficial tool for analyzing biological processes involving Pax3, in particular the development and migration of neural crest cells and melanocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

NETS - A NEURAL NETWORK DEVELOPMENT TOOL, VERSION 3.0 (MACINTOSH VERSION)

Science.gov (United States)

Phillips, T. A.

1994-01-01

NETS, A Tool for the Development and Evaluation of Neural Networks, provides a simulation of Neural Network algorithms plus an environment for developing such algorithms. Neural Networks are a class of systems modeled after the human brain. Artificial Neural Networks are formed from hundreds or thousands of simulated neurons, connected to each other in a manner similar to brain neurons. Problems which involve pattern matching readily fit the class of problems which NETS is designed to solve. NETS uses the back propagation learning method for all of the networks which it creates. The nodes of a network are usually grouped together into clumps called layers. Generally, a network will have an input layer through which the various environment stimuli are presented to the network, and an output layer for determining the network's response. The number of nodes in these two layers is usually tied to some features of the problem being solved. Other layers, which form intermediate stops between the input and output layers, are called hidden layers. NETS allows the user to customize the patterns of connections between layers of a network. NETS also provides features for saving the weight values of a network during the learning process, which allows for more precise control over the learning process. NETS is an interpreter. Its method of execution is the familiar "read-evaluate-print" loop found in interpreted languages such as BASIC and LISP. The user is presented with a prompt which is the simulator's way of asking for input. After a command is issued, NETS will attempt to evaluate the command, which may produce more prompts requesting specific information or an error if the command is not understood. The typical process involved when using NETS consists of translating the problem into a format which uses input/output pairs, designing a network configuration for the problem, and finally training the network with input/output pairs until an acceptable error is reached. NETS

Improve 3D laser scanner measurements accuracy using a FFBP neural network with Widrow-Hoff weight/bias learning function

Science.gov (United States)

Rodríguez-Quiñonez, J. C.; Sergiyenko, O.; Hernandez-Balbuena, D.; Rivas-Lopez, M.; Flores-Fuentes, W.; Basaca-Preciado, L. C.

2014-12-01

Many laser scanners depend on their mechanical construction to guarantee their measurements accuracy, however, the current computational technologies allow us to improve these measurements by mathematical methods implemented in neural networks. In this article we are going to introduce the current laser scanner technologies, give a description of our 3D laser scanner and adjust their measurement error by a previously trained feed forward back propagation (FFBP) neural network with a Widrow-Hoff weight/bias learning function. A comparative analysis with other learning functions such as the Kohonen algorithm and gradient descendent with momentum algorithm is presented. Finally, computational simulations are conducted to verify the performance and method uncertainty in the proposed system.

A neural network technique for remeshing of bone microstructure.

Science.gov (United States)

Fischer, Anath; Holdstein, Yaron

2012-01-01

Today, there is major interest within the biomedical community in developing accurate noninvasive means for the evaluation of bone microstructure and bone quality. Recent improvements in 3D imaging technology, among them development of micro-CT and micro-MRI scanners, allow in-vivo 3D high-resolution scanning and reconstruction of large specimens or even whole bone models. Thus, the tendency today is to evaluate bone features using 3D assessment techniques rather than traditional 2D methods. For this purpose, high-quality meshing methods are required. However, the 3D meshes produced from current commercial systems usually are of low quality with respect to analysis and rapid prototyping. 3D model reconstruction of bone is difficult due to the complexity of bone microstructure. The small bone features lead to a great deal of neighborhood ambiguity near each vertex. The relatively new neural network method for mesh reconstruction has the potential to create or remesh 3D models accurately and quickly. A neural network (NN), which resembles an artificial intelligence (AI) algorithm, is a set of interconnected neurons, where each neuron is capable of making an autonomous arithmetic calculation. Moreover, each neuron is affected by its surrounding neurons through the structure of the network. This paper proposes an extension of the growing neural gas (GNN) neural network technique for remeshing a triangular manifold mesh that represents bone microstructure. This method has the advantage of reconstructing the surface of a genus-n freeform object without a priori knowledge regarding the original object, its topology, or its shape.

Differences in Neural Correlates of Speech Perception in 3 Month Olds at High and Low Risk for Autism Spectrum Disorder.

Science.gov (United States)

Edwards, Laura A; Wagner, Jennifer B; Tager-Flusberg, Helen; Nelson, Charles A

2017-10-01

In this study, we investigated neural precursors of language acquisition as potential endophenotypes of autism spectrum disorder (ASD) in 3-month-old infants at high and low familial ASD risk. Infants were imaged using functional near-infrared spectroscopy while they listened to auditory stimuli containing syllable repetitions; their neural responses were analyzed over left and right temporal regions. While female low risk infants showed initial neural activation that decreased over exposure to repetition-based stimuli, potentially indicating a habituation response to repetition in speech, female high risk infants showed no changes in neural activity over exposure. This finding may indicate a potential neural endophenotype of language development or ASD specific to females at risk for the disorder.

Bioprinting for Neural Tissue Engineering.

Science.gov (United States)

Knowlton, Stephanie; Anand, Shivesh; Shah, Twisha; Tasoglu, Savas

2018-01-01

Bioprinting is a method by which a cell-encapsulating bioink is patterned to create complex tissue architectures. Given the potential impact of this technology on neural research, we review the current state-of-the-art approaches for bioprinting neural tissues. While 2D neural cultures are ubiquitous for studying neural cells, 3D cultures can more accurately replicate the microenvironment of neural tissues. By bioprinting neuronal constructs, one can precisely control the microenvironment by specifically formulating the bioink for neural tissues, and by spatially patterning cell types and scaffold properties in three dimensions. We review a range of bioprinted neural tissue models and discuss how they can be used to observe how neurons behave, understand disease processes, develop new therapies and, ultimately, design replacement tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

Definition of new 3D invariants. Applications to pattern recognition problems with neural networks

International Nuclear Information System (INIS)

Proriol, J.

1996-01-01

We propose a definition of new 3D invariants. Usual pattern recognition methods use 2D descriptions of 3D objects, we propose a 2D approximation of the defined 3D invariants which can be used with neural networks to solve pattern recognition problems. We describe some methods to use the 2 D approximants. This work is an extension of previous 3D invariants used to solve some high energy physics problems. (author)

3. Neural changes in different gravity and ecophysiological environments - A survey

Science.gov (United States)

Slenzka, K.

Neural changes or neuronal plasticity occur after and during different stimulations and inputs in general. Gravity is one major input to the brain transferred from the vestibular system. However, often also direct effects of gravity on the cellular level are discussed. Our group was investigating the influence of different gravity environments on a large variety of neuronal enzymes in the developing fish brain. Long-term space travel or bases on Moon and Mars will have to deal not only with neural changes based on the different gravity environment, but also with potential negative or even toxic changes in the respective life support system. Our goal is now to identify reported enzyme activity changes in the brain based for example on potential toxic drugs or endocrine disruptors in combination with gravity induced changes. In this paper a survey will be undertaken discussing recent results obtained in ecotoxicology, gravitational biology combined with new data from our group regarding potential differences in brain glucose-6-phosphate dehydrogenase of medaka and zebrafish.

Overexpressed Calponin3 by Subsonic Vibration Induces Neural Differentiation of hUC-MSCs by Regulating the Ionotropic Glutamate Receptor.

Science.gov (United States)

Kim, Hyun-Jung; Kim, Jin-Hee; Song, Yeo-Ju; Seo, Young-Kwon; Park, Jung-Keug; Kim, Chan-Wha

2015-09-01

In this study, we used proteomics to investigate the effects of sonic vibration (SV) on mesenchymal stem cells derived from human umbilical cords (hUC-MSCs) during neural differentiation to understand how SV enhances neural differentiation of hUC-MSCs. We investigated the levels of gene and protein related to neural differentiation after 3 or 5 days in a group treated with 40-Hz SV. In addition, protein expression patterns were compared between the control and the 40-Hz SV-treated hUC-MSC groups via a proteomic approach. Among these proteins, calponin3 (CNN3) was confirmed to have 299 % higher expression in the 40-Hz SV stimulated hUC-MSCs group than that in the control by Western blotting. Notably, overexpression of CNN3-GFP in Chinese hamster ovary (CHO)-K1 cells had positive effects on the stability and reorganization of F-actin compared with that in GFP-transfected cells. Moreover, CNN3 changed the morphology of the cells by making a neurite-like form. After being subjected to SV, messenger RNA (mRNA) levels of glutamate receptors such as PSD95, GluR1, and NR1 as well as intracellular calcium levels were upregulated. These results suggest that the activity of glutamate receptors increased because of CNN3 characteristics. Taken together, these results demonstrate that overexpressed CNN3 during SV increases expression of glutamate receptors and promotes functional neural differentiation of hUC-MSCs.

3D porous chitosan scaffolds suit survival and neural differentiation of dental pulp stem cells.

Science.gov (United States)

Feng, Xingmei; Lu, Xiaohui; Huang, Dan; Xing, Jing; Feng, Guijuan; Jin, Guohua; Yi, Xin; Li, Liren; Lu, Yuanzhou; Nie, Dekang; Chen, Xiang; Zhang, Lei; Gu, Zhifeng; Zhang, Xinhua

2014-08-01

A key aspect of cell replacement therapy in brain injury treatment is construction of a suitable biomaterial scaffold that can effectively carry and transport the therapeutic cells to the target area. In the present study, we created small 3D porous chitosan scaffolds through freeze-drying, and showed that these can support and enhance the differentiation of dental pulp stem cells (DPSCs) to nerve cells in vitro. The DPSCs were collected from the dental pulp of adult human third molars. At a swelling rate of ~84.33 ± 10.92 %, the scaffold displayed high porosity and interconnectivity of pores, as revealed by SEM. Cell counting kit-8 assay established the biocompatibility of the chitosan scaffold, supporting the growth and survival of DPSCs. The successful neural differentiation of DPSCs was assayed by RT-PCR, western blotting, and immunofluorescence. We found that the scaffold-attached DPSCs showed high expression of Nestin that decreased sharply following induction of differentiation. Exposure to the differentiation media also increased the expression of neural molecular markers Microtubule-associated protein 2, glial fibrillary acidic protein, and 2',3'-cyclic nucleotide phosphodiesterase. This study demonstrates that the granular 3D chitosan scaffolds are non-cytotoxic, biocompatible, and provide a conducive and favorable micro-environment for attachment, survival, and neural differentiation of DPSCs. These scaffolds have enormous potential to facilitate future advances in treatment of brain injury.

Neurophysiology and neural engineering: a review.

Science.gov (United States)

Prochazka, Arthur

2017-08-01

Neurophysiology is the branch of physiology concerned with understanding the function of neural systems. Neural engineering (also known as neuroengineering) is a discipline within biomedical engineering that uses engineering techniques to understand, repair, replace, enhance, or otherwise exploit the properties and functions of neural systems. In most cases neural engineering involves the development of an interface between electronic devices and living neural tissue. This review describes the origins of neural engineering, the explosive development of methods and devices commencing in the late 1950s, and the present-day devices that have resulted. The barriers to interfacing electronic devices with living neural tissues are many and varied, and consequently there have been numerous stops and starts along the way. Representative examples are discussed. None of this could have happened without a basic understanding of the relevant neurophysiology. I also consider examples of how neural engineering is repaying the debt to basic neurophysiology with new knowledge and insight. Copyright © 2017 the American Physiological Society.

Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans

Directory of Open Access Journals (Sweden)

Jinah Han

2015-02-01

Full Text Available Neural stem cells (NSCs continuously produce new neurons within the adult mammalian hippocampus. NSCs are typically quiescent but activated to self-renew or differentiate into neural progenitor cells. The molecular mechanisms of NSC activation remain poorly understood. Here, we show that adult hippocampal NSCs express vascular endothelial growth factor receptor (VEGFR 3 and its ligand VEGF-C, which activates quiescent NSCs to enter the cell cycle and generate progenitor cells. Hippocampal NSC activation and neurogenesis are impaired by conditional deletion of Vegfr3 in NSCs. Functionally, this is associated with compromised NSC activation in response to VEGF-C and physical activity. In NSCs derived from human embryonic stem cells (hESCs, VEGF-C/VEGFR3 mediates intracellular activation of AKT and ERK pathways that control cell fate and proliferation. These findings identify VEGF-C/VEGFR3 signaling as a specific regulator of NSC activation and neurogenesis in mammals.

Automation of 3D reconstruction of neural tissue from large volume of conventional serial section transmission electron micrographs.

Science.gov (United States)

Mishchenko, Yuriy

2009-01-30

We describe an approach for automation of the process of reconstruction of neural tissue from serial section transmission electron micrographs. Such reconstructions require 3D segmentation of individual neuronal processes (axons and dendrites) performed in densely packed neuropil. We first detect neuronal cell profiles in each image in a stack of serial micrographs with multi-scale ridge detector. Short breaks in detected boundaries are interpolated using anisotropic contour completion formulated in fuzzy-logic framework. Detected profiles from adjacent sections are linked together based on cues such as shape similarity and image texture. Thus obtained 3D segmentation is validated by human operators in computer-guided proofreading process. Our approach makes possible reconstructions of neural tissue at final rate of about 5 microm3/manh, as determined primarily by the speed of proofreading. To date we have applied this approach to reconstruct few blocks of neural tissue from different regions of rat brain totaling over 1000microm3, and used these to evaluate reconstruction speed, quality, error rates, and presence of ambiguous locations in neuropil ssTEM imaging data.

In vitro verification of a 3-D regenerative neural interface design: examination of neurite growth and electrical properties within a bifurcating microchannel structure

NARCIS (Netherlands)

Wieringa, P.A.; Wiertz, Remy; de Weerd, Eddy L; Rutten, Wim

2010-01-01

Toward the development of neuroprosthesis, we propose a 3-D regenerative neural interface design for connecting with the peripheral nervous system. This approach relies on bifurcating microstructures to achieve defasciculated ingrowth patterns and, consequently, high selectivity. In vitro studies

The DNA glycosylases OGG1 and NEIL3 influence differentiation potential, proliferation, and senescence-associated signs in neural stem cells

International Nuclear Information System (INIS)

Reis, Amilcar; Hermanson, Ola

2012-01-01

Highlights: ► DNA glycosylases OGG1 and NEIL3 are required for neural stem cell state. ► No effect on cell viability by OGG1 or NEIL3 knockdown in neural stem cells. ► OGG1 or NEIL3 RNA knockdown result in decreased proliferation and differentiation. ► Increased HP1γ immunoreactivity after NEIL3 knockdown suggests premature senescence. -- Abstract: Embryonic neural stem cells (NSCs) exhibit self-renewal and multipotency as intrinsic characteristics that are key parameters for proper brain development. When cells are challenged by oxidative stress agents the resulting DNA lesions are repaired by DNA glycosylases through the base excision repair (BER) pathway as a means to maintain the fidelity of the genome, and thus, proper cellular characteristics. The functional roles for DNA glycosylases in NSCs have however remained largely unexplored. Here we demonstrate that RNA knockdown of the DNA glycosylases OGG1 and NEIL3 decreased NSC differentiation ability and resulted in decreased expression of both neuronal and astrocytic genes after mitogen withdrawal, as well as the stem cell marker Musashi-1. Furthermore, while cell survival remained unaffected, NEIL3 deficient cells displayed decreased cell proliferation rates along with an increase in HP1γ immunoreactivity, a sign of premature senescence. Our results suggest that DNA glycosylases play multiple roles in governing essential neural stem cell characteristics.

Stability of a neural predictive controller scheme on a neural model

DEFF Research Database (Denmark)

Luther, Jim Benjamin; Sørensen, Paul Haase

2009-01-01

In previous works presenting various forms of neural-network-based predictive controllers, the main emphasis has been on the implementation aspects, i.e. the development of a robust optimization algorithm for the controller, which will be able to perform in real time. However, the stability issue....... The resulting controller is tested on a nonlinear pneumatic servo system.......In previous works presenting various forms of neural-network-based predictive controllers, the main emphasis has been on the implementation aspects, i.e. the development of a robust optimization algorithm for the controller, which will be able to perform in real time. However, the stability issue...... has not been addressed specifically for these controllers. On the other hand a number of results concerning the stability of receding horizon controllers on a nonlinear system exist. In this paper we present a proof of stability for a predictive controller controlling a neural network model...

Neural correlates and neural computations in posterior parietal cortex during perceptual decision-making

Directory of Open Access Journals (Sweden)

Alexander eHuk

2012-10-01

Full Text Available A recent line of work has found remarkable success in relating perceptual decision-making and the spiking activity in the macaque lateral intraparietal area (LIP. In this review, we focus on questions about the neural computations in LIP that are not answered by demonstrations of neural correlates of psychological processes. We highlight three areas of limitations in our current understanding of the precise neural computations that might underlie neural correlates of decisions: (1 empirical questions not yet answered by existing data; (2 implementation issues related to how neural circuits could actually implement the mechanisms suggested by both physiology and psychology; and (3 ecological constraints related to the use of well-controlled laboratory tasks and whether they provide an accurate window on sensorimotor computation. These issues motivate the adoption of a more general encoding-decoding framework that will be fruitful for more detailed contemplation of how neural computations in LIP relate to the formation of perceptual decisions.

Tax and Semaphorin 4D Released from Lymphocytes Infected with Human Lymphotropic Virus Type 1 and Their Effect on Neurite Growth.

Science.gov (United States)

Quintremil, Sebastián; Alberti, Carolina; Rivera, Matías; Medina, Fernando; Puente, Javier; Cartier, Luis; Ramírez, Eugenio; Tanaka, Yuetsu; Valenzuela, M Antonieta

2016-01-01

Human lymphotropic virus type 1 (HTLV-1) is a retrovirus causing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a neurodegenerative central nervous system (CNS) axonopathy. This virus mainly infects CD4(+) T lymphocytes without evidence of neuronal infection. Viral Tax, secreted from infected lymphocytes infiltrated in the CNS, is proposed to alter intracellular pathways related to axonal cytoskeleton dynamics, producing neurological damage. Previous reports showed a higher proteolytic release of soluble Semaphorin 4D (sSEMA-4D) from CD4(+) T cells infected with HTLV-1. Soluble SEMA-4D binds to its receptor Plexin-B1, activating axonal growth collapse pathways in the CNS. In the current study, an increase was found in both SEMA-4D in CD4(+) T cells and sSEMA-4D released to the culture medium of peripheral blood mononuclear cells (PBMCs) from HAM/TSP patients compared to asymptomatic carriers and healthy donors. After a 16-h culture, infected PBMCs showed significantly higher levels of CRMP-2 phosphorylated at Ser(522). The effect was blocked either with anti-Tax or anti-SEMA-4D antibodies. The interaction of Tax and sSEMA-4D was found in secreted medium of PBMCs in patients, which might be associated with a leading role of Tax with the SEMA-4D-Plexin-B1 signaling pathway. In infected PBMCs, the migratory response after transwell assay showed that sSEMA-4D responding cells were CD4(+)Tax(+) T cells with a high CRMP-2 pSer(522) content. In the present study, the participation of Tax-sSEMA-4D in the reduction in neurite growth in PC12 cells produced by MT2 (HTLV-1-infected cell line) culture medium was observed. These results lead to the participation of plexins in the reported effects of infected lymphocytes on neuronal cells.

NETS - A NEURAL NETWORK DEVELOPMENT TOOL, VERSION 3.0 (MACHINE INDEPENDENT VERSION)

Science.gov (United States)

Baffes, P. T.

1994-01-01

NETS, A Tool for the Development and Evaluation of Neural Networks, provides a simulation of Neural Network algorithms plus an environment for developing such algorithms. Neural Networks are a class of systems modeled after the human brain. Artificial Neural Networks are formed from hundreds or thousands of simulated neurons, connected to each other in a manner similar to brain neurons. Problems which involve pattern matching readily fit the class of problems which NETS is designed to solve. NETS uses the back propagation learning method for all of the networks which it creates. The nodes of a network are usually grouped together into clumps called layers. Generally, a network will have an input layer through which the various environment stimuli are presented to the network, and an output layer for determining the network's response. The number of nodes in these two layers is usually tied to some features of the problem being solved. Other layers, which form intermediate stops between the input and output layers, are called hidden layers. NETS allows the user to customize the patterns of connections between layers of a network. NETS also provides features for saving the weight values of a network during the learning process, which allows for more precise control over the learning process. NETS is an interpreter. Its method of execution is the familiar "read-evaluate-print" loop found in interpreted languages such as BASIC and LISP. The user is presented with a prompt which is the simulator's way of asking for input. After a command is issued, NETS will attempt to evaluate the command, which may produce more prompts requesting specific information or an error if the command is not understood. The typical process involved when using NETS consists of translating the problem into a format which uses input/output pairs, designing a network configuration for the problem, and finally training the network with input/output pairs until an acceptable error is reached. NETS

Fundamental study on the interpretation technique for 3-D MT data using neural networks. 2; Neural network wo mochiita sanjigen MT ho data kaishaku gijutsu ni kansuru kisoteki kenkyu. 2

Energy Technology Data Exchange (ETDEWEB)

Fukuoka, K; Kobayashi, T [OYO Corp., Tokyo (Japan); Mogi, T [Kyushu University, Fukuoka (Japan). Faculty of Engineering; Spichak, V

1997-10-22

Behavior of neural networks relative to noise and the constitution of an optimum network are studied for the construction of a 3-D MT data interpretation system using neural networks. In the study, the relationship is examined between the noise level of educational data and the noise level of the neural network to be constructed. After examination it is found that the neural network is effective in interpreting data whose noise level is the same as that of educational data; it cannot correctly interpret data that it has not met in the educational stage even if such data is free of noise; that the optimum number of neurons in a hidden layer is approximately 40 in a network architecture using the current system; and that the neuron gain function enhances recognition capability when a logistic function is used in the hidden layer and a linear function is used in the output layer. 2 refs., 7 figs., 2 tabs.

Expression of the capacity to release [3H]norepinephrine by neural crest cultures

International Nuclear Information System (INIS)

Maxwell, G.D.; Sietz, P.D.

1983-01-01

Cultures of trunk neural crest cells from quail embryos were tested for their ability to release [ 3 H]norepinephrine [( 3 H]NE) in response to depolarization. After 7 days in vitro, exposure of the cultures to either the alkaloid veratridine or 40 mM K+ results in the evoked release of [ 3 H]NE. The release evoked by veratridine is blocked in the presence of tetrodotoxin. The release evoked by increased K+ is blocked by the calcium antagonist cobalt. Release in response to the nicotinic cholinergic agonist 1,1-dimethyl-4-phenylpiperazine was also observed. The amount of evoked release is highly correlated with the number of histochemically demonstrable catecholamine-containing cells in a given culture. Autoradiography reveals that the radioactivity taken up by these cultures is located in a subpopulation of cells whose morphology resembles that of the histochemically detectable catecholamine-containing cell population. Whereas capacity for the release of [ 3 H] NE is readily detectable after 7 days in vitro, it is detectable only with difficulty after 4 days in vitro. There is a greater than 6-fold increase in uptake capacity over the period of 4 to 7 days in vitro. These results demonstrate that neural crest cultures grown without their normal synaptic inputs or targets can exhibit the capacity for stimulus secretion coupling characteristic of synaptic neurotransmitter release

Isointense infant brain MRI segmentation with a dilated convolutional neural network

NARCIS (Netherlands)

Moeskops, P.; Pluim, J.P.W.

2017-01-01

Quantitative analysis of brain MRI at the age of 6 months is difficult because of the limited contrast between white matter and gray matter. In this study, we use a dilated triplanar convolutional neural network in combination with a non-dilated 3D convolutional neural network for the segmentation

Rewiring the taste system.

Science.gov (United States)

Lee, Hojoon; Macpherson, Lindsey J; Parada, Camilo A; Zuker, Charles S; Ryba, Nicholas J P

2017-08-17

In mammals, taste buds typically contain 50-100 tightly packed taste-receptor cells (TRCs), representing all five basic qualities: sweet, sour, bitter, salty and umami. Notably, mature taste cells have life spans of only 5-20 days and, consequently, are constantly replenished by differentiation of taste stem cells. Given the importance of establishing and maintaining appropriate connectivity between TRCs and their partner ganglion neurons (that is, ensuring that a labelled line from sweet TRCs connects to sweet neurons, bitter TRCs to bitter neurons, sour to sour, and so on), we examined how new connections are specified to retain fidelity of signal transmission. Here we show that bitter and sweet TRCs provide instructive signals to bitter and sweet target neurons via different guidance molecules (SEMA3A and SEMA7A). We demonstrate that targeted expression of SEMA3A or SEMA7A in different classes of TRCs produces peripheral taste systems with miswired sweet or bitter cells. Indeed, we engineered mice with bitter neurons that now responded to sweet tastants, sweet neurons that responded to bitter or sweet neurons responding to sour stimuli. Together, these results uncover the basic logic of the wiring of the taste system at the periphery, and illustrate how a labelled-line sensory circuit preserves signalling integrity despite rapid and stochastic turnover of receptor cells.

The DNA glycosylases OGG1 and NEIL3 influence differentiation potential, proliferation, and senescence-associated signs in neural stem cells

Energy Technology Data Exchange (ETDEWEB)

Reis, Amilcar [Linnaeus Center in Developmental Biology for Regenerative Medicine (DBRM), Department of Neuroscience, Karolinska Institutet, SE 17177 Stockholm (Sweden); Hermanson, Ola, E-mail: ola.hermanson@ki.se [Linnaeus Center in Developmental Biology for Regenerative Medicine (DBRM), Department of Neuroscience, Karolinska Institutet, SE 17177 Stockholm (Sweden)

2012-07-13

Highlights: Black-Right-Pointing-Pointer DNA glycosylases OGG1 and NEIL3 are required for neural stem cell state. Black-Right-Pointing-Pointer No effect on cell viability by OGG1 or NEIL3 knockdown in neural stem cells. Black-Right-Pointing-Pointer OGG1 or NEIL3 RNA knockdown result in decreased proliferation and differentiation. Black-Right-Pointing-Pointer Increased HP1{gamma} immunoreactivity after NEIL3 knockdown suggests premature senescence. -- Abstract: Embryonic neural stem cells (NSCs) exhibit self-renewal and multipotency as intrinsic characteristics that are key parameters for proper brain development. When cells are challenged by oxidative stress agents the resulting DNA lesions are repaired by DNA glycosylases through the base excision repair (BER) pathway as a means to maintain the fidelity of the genome, and thus, proper cellular characteristics. The functional roles for DNA glycosylases in NSCs have however remained largely unexplored. Here we demonstrate that RNA knockdown of the DNA glycosylases OGG1 and NEIL3 decreased NSC differentiation ability and resulted in decreased expression of both neuronal and astrocytic genes after mitogen withdrawal, as well as the stem cell marker Musashi-1. Furthermore, while cell survival remained unaffected, NEIL3 deficient cells displayed decreased cell proliferation rates along with an increase in HP1{gamma} immunoreactivity, a sign of premature senescence. Our results suggest that DNA glycosylases play multiple roles in governing essential neural stem cell characteristics.

Musicians' Enhanced Neural Differentiation of Speech Sounds Arises Early in Life: Developmental Evidence from Ages 3 to 30

Science.gov (United States)

Strait, Dana L.; O'Connell, Samantha; Parbery-Clark, Alexandra; Kraus, Nina

2014-01-01

The perception and neural representation of acoustically similar speech sounds underlie language development. Music training hones the perception of minute acoustic differences that distinguish sounds; this training may generalize to speech processing given that adult musicians have enhanced neural differentiation of similar speech syllables compared with nonmusicians. Here, we asked whether this neural advantage in musicians is present early in life by assessing musically trained and untrained children as young as age 3. We assessed auditory brainstem responses to the speech syllables /ba/ and /ga/ as well as auditory and visual cognitive abilities in musicians and nonmusicians across 3 developmental time-points: preschoolers, school-aged children, and adults. Cross-phase analyses objectively measured the degree to which subcortical responses differed to these speech syllables in musicians and nonmusicians for each age group. Results reveal that musicians exhibit enhanced neural differentiation of stop consonants early in life and with as little as a few years of training. Furthermore, the extent of subcortical stop consonant distinction correlates with auditory-specific cognitive abilities (i.e., auditory working memory and attention). Results are interpreted according to a corticofugal framework for auditory learning in which subcortical processing enhancements are engendered by strengthened cognitive control over auditory function in musicians. PMID:23599166

Semaphorin 4C Protects against Allergic Inflammation: Requirement of Regulatory CD138+ Plasma Cells.

Science.gov (United States)

Xue, Di; Kaufman, Gabriel N; Dembele, Marieme; Beland, Marianne; Massoud, Amir H; Mindt, Barbara C; Fiter, Ryan; Fixman, Elizabeth D; Martin, James G; Friedel, Roland H; Divangahi, Maziar; Fritz, Jörg H; Mazer, Bruce D

2017-01-01

The regulatory properties of B cells have been studied in autoimmune diseases; however, their role in allergic diseases is poorly understood. We demonstrate that Semaphorin 4C (Sema4C), an axonal guidance molecule, plays a crucial role in B cell regulatory function. Mice deficient in Sema4C exhibited increased airway inflammation after allergen exposure, with massive eosinophilic lung infiltrates and increased Th2 cytokines. This phenotype was reproduced by mixed bone marrow chimeric mice with Sema4C deficient only in B cells, indicating that B lymphocytes were the key cells affected by the absence of Sema4C expression in allergic inflammation. We determined that Sema4C-deficient CD19 + CD138 + cells exhibited decreased IL-10 and increased IL-4 expression in vivo and in vitro. Adoptive transfer of Sema4c -/- CD19 + CD138 + cells induced marked pulmonary inflammation, eosinophilia, and increased bronchoalveolar lavage fluid IL-4 and IL-5, whereas adoptive transfer of wild-type CD19 + CD138 + IL-10 + cells dramatically decreased allergic airway inflammation in wild-type and Sema4c -/- mice. This study identifies a novel pathway by which Th2-mediated immune responses are regulated. It highlights the importance of plasma cells as regulatory cells in allergic inflammation and suggests that CD138 + B cells contribute to cytokine balance and are important for maintenance of immune homeostasis in allergic airways disease. Furthermore, we demonstrate that Sema4C is critical for optimal regulatory cytokine production in CD138 + B cells. Copyright © 2016 by The American Association of Immunologists, Inc.

Real time track finding in a drift chamber with a VLSI neural network

International Nuclear Information System (INIS)

Lindsey, C.S.; Denby, B.; Haggerty, H.; Johns, K.

1992-01-01

In a test setup, a hardware neural network determined track parameters of charged particles traversing a drift chamber. Voltages proportional to the drift times in 6 cells of the 3-layer chamber were inputs to the Intel ETANN neural network chip which had been trained to give the slope and intercept of tracks. We compare network track parameters to those obtained from off-line track fits. To our knowledge this is the first on-line application of a VLSI neural network to a high energy physics detector. This test explored the potential of the chip and the practical problems of using it in a real world setting. We compare the chip performance to a neural network simulation on a conventional computer. We discuss possible applications of the chip in high energy physics detector triggers. (orig.)

Deconvolution using a neural network

Energy Technology Data Exchange (ETDEWEB)

Lehman, S.K.

1990-11-15

Viewing one dimensional deconvolution as a matrix inversion problem, we compare a neural network backpropagation matrix inverse with LMS, and pseudo-inverse. This is a largely an exercise in understanding how our neural network code works. 1 ref.

Signal Processing and Neural Network Simulator

Science.gov (United States)

Tebbe, Dennis L.; Billhartz, Thomas J.; Doner, John R.; Kraft, Timothy T.

1995-04-01

The signal processing and neural network simulator (SPANNS) is a digital signal processing simulator with the capability to invoke neural networks into signal processing chains. This is a generic tool which will greatly facilitate the design and simulation of systems with embedded neural networks. The SPANNS is based on the Signal Processing WorkSystemTM (SPWTM), a commercial-off-the-shelf signal processing simulator. SPW provides a block diagram approach to constructing signal processing simulations. Neural network paradigms implemented in the SPANNS include Backpropagation, Kohonen Feature Map, Outstar, Fully Recurrent, Adaptive Resonance Theory 1, 2, & 3, and Brain State in a Box. The SPANNS was developed by integrating SAIC's Industrial Strength Neural Networks (ISNN) Software into SPW.

Axon guidance in the developing ocular motor system and Duane retraction syndrome depends on Semaphorin signaling via alpha2-chimaerin

Science.gov (United States)

Ferrario, Juan E.; Baskaran, Pranetha; Clark, Christopher; Hendry, Aenea; Lerner, Oleg; Hintze, Mark; Allen, James; Chilton, John K.; Guthrie, Sarah

2012-01-01

Eye movements depend on correct patterns of connectivity between cranial motor axons and the extraocular muscles. Despite the clinical importance of the ocular motor system, little is known of the molecular mechanisms underlying its development. We have recently shown that mutations in the Chimaerin-1 gene encoding the signaling protein α2-chimaerin (α2-chn) perturb axon guidance in the ocular motor system and lead to the human eye movement disorder, Duane retraction syndrome (DRS). The axon guidance cues that lie upstream of α2-chn are unknown; here we identify candidates to be the Semaphorins (Sema) 3A and 3C, acting via the PlexinA receptors. Sema3A/C are expressed in and around the developing extraocular muscles and cause growth cone collapse of oculomotor neurons in vitro. Furthermore, RNAi knockdown of α2-chn or PlexinAs in oculomotor neurons abrogates Sema3A/C-dependent growth cone collapse. In vivo knockdown of endogenous PlexinAs or α2-chn function results in stereotypical oculomotor axon guidance defects, which are reminiscent of DRS, whereas expression of α2-chn gain-of-function constructs can rescue PlexinA loss of function. These data suggest that α2-chn mediates Sema3–PlexinA repellent signaling. We further show that α2-chn is required for oculomotor neurons to respond to CXCL12 and hepatocyte growth factor (HGF), which are growth promoting and chemoattractant during oculomotor axon guidance. α2-chn is therefore a potential integrator of different types of guidance information to orchestrate ocular motor pathfinding. DRS phenotypes can result from incorrect regulation of this signaling pathway. PMID:22912401

Performance Parameters Analysis of an XD3P Peugeot Engine Using Artificial Neural Networks (ANN) Concept in MATLAB

Science.gov (United States)

Rangaswamy, T.; Vidhyashankar, S.; Madhusudan, M.; Bharath Shekar, H. R.

2015-04-01

The current trends of engineering follow the basic rule of innovation in mechanical engineering aspects. For the engineers to be efficient, problem solving aspects need to be viewed in a multidimensional perspective. One such methodology implemented is the fusion of technologies from other disciplines in order to solve the problems. This paper mainly deals with the application of Neural Networks in order to analyze the performance parameters of an XD3P Peugeot engine (used in Ministry of Defence). The basic propaganda of the work is divided into two main working stages. In the former stage, experimentation of an IC engine is carried out in order to obtain the primary data. In the latter stage the primary database formed is used to design and implement a predictive neural network in order to analyze the output parameters variation with respect to each other. A mathematical governing equation for the neural network is obtained. The obtained polynomial equation describes the characteristic behavior of the built neural network system. Finally, a comparative study of the results is carried out.

Analysis of surface ozone using a recurrent neural network.

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Biancofiore, Fabio; Verdecchia, Marco; Di Carlo, Piero; Tomassetti, Barbara; Aruffo, Eleonora; Busilacchio, Marcella; Bianco, Sebastiano; Di Tommaso, Sinibaldo; Colangeli, Carlo

2015-05-01

Hourly concentrations of ozone (O₃) and nitrogen dioxide (NO₂) have been measured for 16 years, from 1998 to 2013, in a seaside town in central Italy. The seasonal trends of O₃ and NO₂ recorded in this period have been studied. Furthermore, we used the data collected during one year (2005), to define the characteristics of a multiple linear regression model and a neural network model. Both models are used to model the hourly O₃ concentration, using, two scenarios: 1) in the first as inputs, only meteorological parameters and 2) in the second adding photochemical parameters at those of the first scenario. In order to evaluate the performance of the model four statistical criteria are used: correlation coefficient, fractional bias, normalized mean squared error and a factor of two. All the criteria show that the neural network gives better results, compared to the regression model, in all the model scenarios. Predictions of O₃ have been carried out by many authors using a feed forward neural architecture. In this paper we show that a recurrent architecture significantly improves the performances of neural predictors. Using only the meteorological parameters as input, the recurrent architecture shows performance better than the multiple linear regression model that uses meteorological and photochemical data as input, making the neural network model with recurrent architecture a more useful tool in areas where only weather measurements are available. Finally, we used the neural network model to forecast the O₃ hourly concentrations 1, 3, 6, 12, 24 and 48 h ahead. The performances of the model in predicting O₃ levels are discussed. Emphasis is given to the possibility of using the neural network model in operational ways in areas where only meteorological data are available, in order to predict O₃ also in sites where it has not been measured yet. Copyright © 2015 Elsevier B.V. All rights reserved.

A primary leiomyoma in the neural foramen of the lumbar spine: a case report

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Jang, Jong Chang; Kang, Byeong Seong; Kim, Young Min; Park, Moon Soo; Jeong, Ae Kyung; Yang, Myeon Jun; Hwang, Jae Cheol [University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan (Korea, Republic of)

2007-12-15

A primary leiomyoma in the neural foramen of the lumbar spine is a very rare condition. We examined a 23-year-old female presented with back and right flank pain. A plain radiography showed a well-defined, osteolytic lesion in the L3 body. In addition, MR images showed a mass lesion with intense enhancement, after intravenous injection with contrast material, in the right neural foramen at the L2/3 level. A histopathologic examination of the resected specimen revealed a benign leiomyoma.

The Effects of Low-Dose Bisphenol A and Bisphenol F on Neural Differentiation of a Fetal Brain-Derived Neural Progenitor Cell Line.

Science.gov (United States)

Fujiwara, Yuki; Miyazaki, Wataru; Koibuchi, Noriyuki; Katoh, Takahiko

2018-01-01

Environmental chemicals are known to disrupt the endocrine system in humans and to have adverse effects on several organs including the developing brain. Recent studies indicate that exposure to environmental chemicals during gestation can interfere with neuronal differentiation, subsequently affecting normal brain development in newborns. Xenoestrogen, bisphenol A (BPA), which is widely used in plastic products, is one such chemical. Adverse effects of exposure to BPA during pre- and postnatal periods include the disruption of brain function. However, the effect of BPA on neural differentiation remains unclear. In this study, we explored the effects of BPA or bisphenol F (BPF), an alternative compound for BPA, on neural differentiation using ReNcell, a human fetus-derived neural progenitor cell line. Maintenance in growth factor-free medium initiated the differentiation of ReNcell to neuronal cells including neurons, astrocytes, and oligodendrocytes. We exposed the cells to BPA or BPF for 3 days from the period of initiation and performed real-time PCR for neural markers such as β III-tubulin and glial fibrillary acidic protein (GFAP), and Olig2. The β III-tubulin mRNA level decreased in response to BPA, but not BPF, exposure. We also observed that the number of β III-tubulin-positive cells in the BPA-exposed group was less than that of the control group. On the other hand, there were no changes in the MAP2 mRNA level. These results indicate that BPA disrupts neural differentiation in human-derived neural progenitor cells, potentially disrupting brain development.

The Effects of Low-Dose Bisphenol A and Bisphenol F on Neural Differentiation of a Fetal Brain-Derived Neural Progenitor Cell Line

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Yuki Fujiwara

2018-02-01

Full Text Available Environmental chemicals are known to disrupt the endocrine system in humans and to have adverse effects on several organs including the developing brain. Recent studies indicate that exposure to environmental chemicals during gestation can interfere with neuronal differentiation, subsequently affecting normal brain development in newborns. Xenoestrogen, bisphenol A (BPA, which is widely used in plastic products, is one such chemical. Adverse effects of exposure to BPA during pre- and postnatal periods include the disruption of brain function. However, the effect of BPA on neural differentiation remains unclear. In this study, we explored the effects of BPA or bisphenol F (BPF, an alternative compound for BPA, on neural differentiation using ReNcell, a human fetus-derived neural progenitor cell line. Maintenance in growth factor-free medium initiated the differentiation of ReNcell to neuronal cells including neurons, astrocytes, and oligodendrocytes. We exposed the cells to BPA or BPF for 3 days from the period of initiation and performed real-time PCR for neural markers such as β III-tubulin and glial fibrillary acidic protein (GFAP, and Olig2. The β III-tubulin mRNA level decreased in response to BPA, but not BPF, exposure. We also observed that the number of β III-tubulin-positive cells in the BPA-exposed group was less than that of the control group. On the other hand, there were no changes in the MAP2 mRNA level. These results indicate that BPA disrupts neural differentiation in human-derived neural progenitor cells, potentially disrupting brain development.

A new perspective on behavioral inconsistency and neural noise in aging: Compensatory speeding of neural communication

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S. Lee Hong

2012-09-01

Full Text Available This paper seeks to present a new perspective on the aging brain. Here, we make connections between two key phenomena of brain aging: 1 increased neural noise or random background activity; and 2 slowing of brain activity. Our perspective proposes the possibility that the slowing of neural processing due to decreasing nerve conduction velocities leads to a compensatory speeding of neuron firing rates. These increased firing rates lead to a broader distribution of power in the frequency spectrum of neural oscillations, which we propose, can just as easily be interpreted as neural noise. Compensatory speeding of neural activity, as we present, is constrained by the: A availability of metabolic energy sources; and B competition for frequency bandwidth needed for neural communication. We propose that these constraints lead to the eventual inability to compensate for age-related declines in neural function that are manifested clinically as deficits in cognition, affect, and motor behavior.

Semaphorin4D Drives CD8+ T-Cell Lesional Trafficking in Oral Lichen Planus via CXCL9/CXCL10 Upregulations in Oral Keratinocytes.

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Ke, Yao; Dang, Erle; Shen, Shengxian; Zhang, Tongmei; Qiao, Hongjiang; Chang, Yuqian; Liu, Qing; Wang, Gang

2017-11-01

Chemokine-mediated CD8 + T-cell recruitment is an essential but not well-established event for the persistence of oral lichen planus (OLP). Semaphorin 4D (Sema4D)/CD100 is implicated in immune dysfunction, chemokine modulation, and cell migration, which are critical aspects for OLP progression, but its implication in OLP pathogenesis has not been determined. In this study, we sought to explicate the effect of Sema4D on human oral keratinocytes and its capacity to drive CD8 + T-cell lesional trafficking via chemokine modulation. We found that upregulations of sSema4D in OLP tissues and blood were positively correlated with disease severity and activity. In vitro observation revealed that Sema4D induced C-X-C motif chemokine ligand 9/C-X-C motif chemokine ligand 10 production by binding to plexin-B1 via protein kinase B-NF-κB cascade in human oral keratinocytes, which elicited OLP CD8 + T-cell migration. We also confirmed using clinical samples that elevated C-X-C motif chemokine ligand 9/C-X-C motif chemokine ligand 10 levels were positively correlated with sSema4D levels in OLP lesions and serum. Notably, we determined matrix metalloproteinase-9 as a new proteolytic enzyme for the cleavage of sSema4D from the T-cell surface, which may contribute to the high levels of sSema4D in OLP lesions and serum. Our findings conclusively revealed an amplification feedback loop involving T cells, chemokines, and Sema4D-dependent signal that promotes OLP progression. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

T1r3 taste receptor involvement in gustatory neural responses to ethanol and oral ethanol preference.

Science.gov (United States)

Brasser, Susan M; Norman, Meghan B; Lemon, Christian H

2010-05-01

Elevated alcohol consumption is associated with enhanced preference for sweet substances across species and may be mediated by oral alcohol-induced activation of neurobiological substrates for sweet taste. Here, we directly examined the contribution of the T1r3 receptor protein, important for sweet taste detection in mammals, to ethanol intake and preference and the neural processing of ethanol taste by measuring behavioral and central neurophysiological responses to oral alcohol in T1r3 receptor-deficient mice and their C57BL/6J background strain. T1r3 knockout and wild-type mice were tested in behavioral preference assays for long-term voluntary intake of a broad concentration range of ethanol, sucrose, and quinine. For neurophysiological experiments, separate groups of mice of each genotype were anesthetized, and taste responses to ethanol and stimuli of different taste qualities were electrophysiologically recorded from gustatory neurons in the nucleus of the solitary tract. Mice lacking the T1r3 receptor were behaviorally indifferent to alcohol (i.e., ∼50% preference values) at concentrations typically preferred by wild-type mice (5-15%). Central neural taste responses to ethanol in T1r3-deficient mice were significantly lower compared with C57BL/6J controls, a strain for which oral ethanol stimulation produced a concentration-dependent activation of sweet-responsive NTS gustatory neurons. An attenuated difference in ethanol preference between knockouts and controls at concentrations >15% indicated that other sensory and/or postingestive effects of ethanol compete with sweet taste input at high concentrations. As expected, T1r3 knockouts exhibited strongly suppressed behavioral and neural taste responses to sweeteners but did not differ from wild-type mice in responses to prototypic salt, acid, or bitter stimuli. These data implicate the T1r3 receptor in the sensory detection and transduction of ethanol taste.

A neural network model of the relativistic electron flux at geosynchronous orbit

International Nuclear Information System (INIS)

Koons, H.C.; Gorney, D.J.

1991-01-01

A neural network has been developed to model the temporal variations of relativistic (>3 MeV) electrons at geosynchronous orbit based on model inputs consisting of 10 consecutive days of the daily sum of the planetary magnetic index ΣKp. The neural network consists of three layers of neurons, containing 10 neurons in the input layer, 6 neurons in a hidden layer, and 1 output neuron. The output is a prediction of the daily-averaged electron flux for the tenth day. The neural network was trained using 62 days of data from July 1, 1984, through August 31, 1984, from the SEE spectrometer on the geosynchronous spacecraft 1982-019. The performance of the model was measured by comparing model outputs with measured fluxes over a 6-year period from April 19, 1982, to June 4, 1988. For the entire data set the rms logarithmic error of the neural network is 0.76, and the average logarithmic error is 0.58. The neural network is essentially zero biased, and for accumulation intervals of 3 days or longer the average logarithmic error is less than 0.1. The neural network provides results that are significantly more accurate than those from linear prediction filters. The model has been used to simulate conditions which are rarely observed in nature, such as long periods of quiet (ΣKp = 0) and ideal impulses. It has also been used to make reasonably accurate day-ahead forecasts of the relativistic electron flux at geosynchronous orbit

The response of early neural genes to FGF signaling or inhibition of BMP indicate the absence of a conserved neural induction module

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Rogers Crystal D

2011-12-01

Full Text Available Abstract Background The molecular mechanism that initiates the formation of the vertebrate central nervous system has long been debated. Studies in Xenopus and mouse demonstrate that inhibition of BMP signaling is sufficient to induce neural tissue in explants or ES cells respectively, whereas studies in chick argue that instructive FGF signaling is also required for the expression of neural genes. Although additional signals may be involved in neural induction and patterning, here we focus on the roles of BMP inhibition and FGF8a. Results To address the question of necessity and sufficiency of BMP inhibition and FGF signaling, we compared the temporal expression of the five earliest genes expressed in the neuroectoderm and determined their requirements for induction at the onset of neural plate formation in Xenopus. Our results demonstrate that the onset and peak of expression of the genes vary and that they have different regulatory requirements and are therefore unlikely to share a conserved neural induction regulatory module. Even though all require inhibition of BMP for expression, some also require FGF signaling; expression of the early-onset pan-neural genes sox2 and foxd5α requires FGF signaling while other early genes, sox3, geminin and zicr1 are induced by BMP inhibition alone. Conclusions We demonstrate that BMP inhibition and FGF signaling induce neural genes independently of each other. Together our data indicate that although the spatiotemporal expression patterns of early neural genes are similar, the mechanisms involved in their expression are distinct and there are different signaling requirements for the expression of each gene.

Spinal Cord Stimulation (SCS) with Anatomically Guided (3D) Neural Targeting Shows Superior Chronic Axial Low Back Pain Relief Compared to Traditional SCS-LUMINA Study.

Science.gov (United States)

Veizi, Elias; Hayek, Salim M; North, James; Brent Chafin, T; Yearwood, Thomas L; Raso, Louis; Frey, Robert; Cairns, Kevin; Berg, Anthony; Brendel, John; Haider, Nameer; McCarty, Matthew; Vucetic, Henry; Sherman, Alden; Chen, Lilly; Mekel-Bobrov, Nitzan

2017-08-01

The aim of this study was to determine whether spinal cord stimulation (SCS) using 3D neural targeting provided sustained overall and low back pain relief in a broad routine clinical practice population. This was a multicenter, open-label observational study with an observational arm and retrospective analysis of a matched cohort. After IPG implantation, programming was done using a patient-specific, model-based algorithm to adjust for lead position (3D neural targeting) or previous generation software (traditional). Demographics, medical histories, SCS parameters, pain locations, pain intensities, disabilities, and safety data were collected for all patients. A total of 213 patients using 3D neural targeting were included, with a trial-to-implant ratio of 86%. Patients used seven different lead configurations, with 62% receiving 24 to 32 contacts, and a broad range of stimulation parameters utilizing a mean of 14.3 (±6.1) contacts. At 24 months postimplant, pain intensity decreased significantly from baseline (ΔNRS = 4.2, N = 169, P  pain subgroup (ΔNRS = 5.3, N = 91, P  low back pain also decreased significantly from baseline to 24 months (ΔNRS = 4.1, N = 70, P  pain responder rates of 51% (traditional SCS) and 74% (neural targeting SCS) and axial low back pain responder rates of 41% and 71% in the traditional SCS and neural targeting SCS cohorts, respectively. Lastly, complications occurred in a total of 33 of the 213 patients, with a 1.6% lead replacement rate and a 1.6% explant rate. Our results suggest that 3D neural targeting SCS and its associated hardware flexibility provide effective treatment for both chronic leg and chronic axial low back pain that is significantly superior to traditional SCS. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Construction of a Piezoresistive Neural Sensor Array

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Carlson, W. B.; Schulze, W. A.; Pilgrim, P. M.

1996-01-01

The construction of a piezoresistive - piezoelectric sensor (or actuator) array is proposed using 'neural' connectivity for signal recognition and possible actuation functions. A closer integration of the sensor and decision functions is necessary in order to achieve intrinsic identification within the sensor. A neural sensor is the next logical step in development of truly 'intelligent' arrays. This proposal will integrate 1-3 polymer piezoresistors and MLC electroceramic devices for applications involving acoustic identification. The 'intelligent' piezoresistor -piezoelectric system incorporates printed resistors, composite resistors, and a feedback for the resetting of resistances. A model of a design is proposed in order to simulate electromechanical resistor interactions. The goal of optimizing a sensor geometry for improving device reliability, training, & signal identification capabilities is the goal of this work. At present, studies predict performance of a 'smart' device with a significant control of 'effective' compliance over a narrow pressure range due to a piezoresistor percolation threshold. An interesting possibility may be to use an array of control elements to shift the threshold function in order to change the level of resistance in a neural sensor array for identification, or, actuation applications. The proposed design employs elements of: (1) conductor loaded polymers for a 'fast' RC time constant response; and (2) multilayer ceramics for actuation or sensing and shifting of resistance in the polymer. Other material possibilities also exist using magnetoresistive layered systems for shifting the resistance. It is proposed to use a neural net configuration to test and to help study the possible changes required in the materials design of these devices. Numerical design models utilize electromechanical elements, in conjunction with structural elements in order to simulate piezoresistively controlled actuators and changes in resistance of sensors

Infrared neural stimulation (INS) inhibits electrically evoked neural responses in the deaf white cat

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Richter, Claus-Peter; Rajguru, Suhrud M.; Robinson, Alan; Young, Hunter K.

2014-03-01

Infrared neural stimulation (INS) has been used in the past to evoke neural activity from hearing and partially deaf animals. All the responses were excitatory. In Aplysia californica, Duke and coworkers demonstrated that INS also inhibits neural responses [1], which similar observations were made in the vestibular system [2, 3]. In deaf white cats that have cochleae with largely reduced spiral ganglion neuron counts and a significant degeneration of the organ of Corti, no cochlear compound action potentials could be observed during INS alone. However, the combined electrical and optical stimulation demonstrated inhibitory responses during irradiation with infrared light.

ZDHHC3 Tyrosine Phosphorylation Regulates Neural Cell Adhesion Molecule Palmitoylation

Science.gov (United States)

Lievens, Patricia Marie-Jeanne; Kuznetsova, Tatiana; Kochlamazashvili, Gaga; Cesca, Fabrizia; Gorinski, Natalya; Galil, Dalia Abdel; Cherkas, Volodimir; Ronkina, Natalia; Lafera, Juri; Gaestel, Matthias

2016-01-01

The neural cell adhesion molecule (NCAM) mediates cell-cell and cell-matrix adhesion. It is broadly expressed in the nervous system and regulates neurite outgrowth, synaptogenesis, and synaptic plasticity. Previous in vitro studies revealed that palmitoylation of NCAM is required for fibroblast growth factor 2 (FGF2)-stimulated neurite outgrowth and identified the zinc finger DHHC (Asp-His-His-Cys)-containing proteins ZDHHC3 and ZDHHC7 as specific NCAM-palmitoylating enzymes. Here, we verified that FGF2 controlled NCAM palmitoylation in vivo and investigated molecular mechanisms regulating NCAM palmitoylation by ZDHHC3. Experiments with overexpression and pharmacological inhibition of FGF receptor (FGFR) and Src revealed that these kinases control tyrosine phosphorylation of ZDHHC3 and that ZDHHC3 is phosphorylated by endogenously expressed FGFR and Src proteins. By site-directed mutagenesis, we found that Tyr18 is an FGFR1-specific ZDHHC3 phosphorylation site, while Tyr295 and Tyr297 are specifically phosphorylated by Src kinase in cell-based and cell-free assays. Abrogation of tyrosine phosphorylation increased ZDHHC3 autopalmitoylation, enhanced interaction with NCAM, and upregulated NCAM palmitoylation. Expression of ZDHHC3 with tyrosine mutated in cultured hippocampal neurons promoted neurite outgrowth. Our findings for the first time highlight that FGFR- and Src-mediated tyrosine phosphorylation of ZDHHC3 modulates ZDHHC3 enzymatic activity and plays a role in neuronal morphogenesis. PMID:27247265

Structural Analysis of Three-dimensional Human Neural Tissue derived from Induced Pluripotent Stem Cells

DEFF Research Database (Denmark)

Terrence Brooks, Patrick; Rasmussen, Mikkel Aabech; Hyttel, Poul

2016-01-01

Objective: The present study aimed at establishing a method for production of a three-dimensional (3D) human neural tissue derived from induced pluripotent stem cells (iPSCs) and analyzing the outcome by a combination of tissue ultrastructure and expression of neural markers. Methods: A two......-step cell culture procedure was implemented by subjecting human iPSCs to a 3D scaffoldbased neural differentiation protocol. First, neural fate-inducing small molecules were used to create a neuroepithelial monolayer. Second, the monolayer was trypsinized into single cells and seeded into a porous...... polystyrene scaffold and further cultured to produce a 3D neural tissue. The neural tissue was characterized by a combination of immunohistochemistry and transmission electron microscopy (TEM). Results: iPSCs developed into a 3D neural tissue expressing markers for neural progenitor cells, early neural...

A Streaming PCA VLSI Chip for Neural Data Compression.

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Wu, Tong; Zhao, Wenfeng; Guo, Hongsun; Lim, Hubert H; Yang, Zhi

2017-12-01

Neural recording system miniaturization and integration with low-power wireless technologies require compressing neural data before transmission. Feature extraction is a procedure to represent data in a low-dimensional space; its integration into a recording chip can be an efficient approach to compress neural data. In this paper, we propose a streaming principal component analysis algorithm and its microchip implementation to compress multichannel local field potential (LFP) and spike data. The circuits have been designed in a 65-nm CMOS technology and occupy a silicon area of 0.06 mm. Throughout the experiments, the chip compresses LFPs by 10 at the expense of as low as 1% reconstruction errors and 144-nW/channel power consumption; for spikes, the achieved compression ratio is 25 with 8% reconstruction errors and 3.05-W/channel power consumption. In addition, the algorithm and its hardware architecture can swiftly adapt to nonstationary spiking activities, which enables efficient hardware sharing among multiple channels to support a high-channel count recorder.

In vivo impact of Dlx3 conditional inactivation in Neural Crest-Derived Craniofacial Bones

Science.gov (United States)

Duverger, Olivier; Isaac, Juliane; Zah, Angela; Hwang, Joonsung; Berdal, Ariane; Lian, Jane B.; Morasso, Maria I.

2012-01-01

Mutations in DLX3 in humans lead to defects in craniofacial and appendicular bones, yet the in vivo activity related to Dlx3 function during normal skeletal development have not been fully elucidated. Here we used a conditional knockout approach to analyze the effects of neural crest deletion of Dlx3 on craniofacial bones development. At birth, mutant mice exhibit a normal overall positioning of the skull bones, but a change in the shape of the calvaria was observed. Molecular analysis of the genes affected in the frontal bones and mandibles from these mice identified several bone markers known to affect bone development, with a strong prediction for increased bone formation and mineralization in vivo. Interestingly, while a subset of these genes were similarly affected in frontal bones and mandibles (Sost, Mepe, Bglap, Alp, Ibsp, Agt), several genes, including Lect1 and Calca, were specifically affected in frontal bones. Consistent with these molecular alterations, cells isolated from the frontal bone of mutant mice exhibited increased differentiation and mineralization capacities ex vivo, supporting cell autonomous defects in neural crest cells. However, adult mutant animals exhibited decreased bone mineral density in both mandibles and calvaria, as well as a significant increase in bone porosity. Together, these observations suggest that mature osteoblasts in the adult respond to signals that regulate adult bone mass and remodeling. This study provides new downstream targets for Dlx3 in craniofacial bone, and gives additional evidence of the complex regulation of bone formation and homeostasis in the adult skeleton. PMID:22886599

Disruption of Aedes aegypti olfactory system development through chitosan/siRNA nanoparticle targeting of semaphorin-1a.

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Keshava Mysore

Full Text Available Despite the devastating impact of mosquito-borne illnesses on human health, surprisingly little is known about mosquito developmental biology, including development of the olfactory system, a tissue of vector importance. Analysis of mosquito olfactory developmental genetics has been hindered by a lack of means to target specific genes during the development of this sensory system. In this investigation, chitosan/siRNA nanoparticles were used to target semaphorin-1a (sema1a during olfactory system development in the dengue and yellow fever vector mosquito Aedes aegypti. Immunohistochemical analyses and anterograde tracing of antennal sensory neurons, which were used to track the progression of olfactory development in this species, revealed antennal lobe defects in sema1a knockdown fourth instar larvae. These findings, which correlated with a larval odorant tracking behavioral phenotype, identified previously unreported roles for Sema1a in the developing insect larval olfactory system. Analysis of sema1a knockdown pupae also revealed a number of olfactory phenotypes, including olfactory receptor neuron targeting and projection neuron defects coincident with a collapse in the structure and shape of the antennal lobe and individual glomeruli. This study, which is to our knowledge the first functional genetic analysis of insect olfactory development outside of D. melanogaster, identified critical roles for Sema1a during Ae. aegypti larval and pupal olfactory development and advocates the use of chitosan/siRNA nanoparticles as an effective means of targeting genes during post-embryonic Ae. aegypti development. Use of siRNA nanoparticle methodology to understand sensory developmental genetics in mosquitoes will provide insight into the evolutionary conservation and divergence of key developmental genes which could be exploited in the development of both common and species-specific means for intervention.

Automatic detection of kidney in 3D pediatric ultrasound images using deep neural networks

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Tabrizi, Pooneh R.; Mansoor, Awais; Biggs, Elijah; Jago, James; Linguraru, Marius George

2018-02-01

Ultrasound (US) imaging is the routine and safe diagnostic modality for detecting pediatric urology problems, such as hydronephrosis in the kidney. Hydronephrosis is the swelling of one or both kidneys because of the build-up of urine. Early detection of hydronephrosis can lead to a substantial improvement in kidney health outcomes. Generally, US imaging is a challenging modality for the evaluation of pediatric kidneys with different shape, size, and texture characteristics. The aim of this study is to present an automatic detection method to help kidney analysis in pediatric 3DUS images. The method localizes the kidney based on its minimum volume oriented bounding box) using deep neural networks. Separate deep neural networks are trained to estimate the kidney position, orientation, and scale, making the method computationally efficient by avoiding full parameter training. The performance of the method was evaluated using a dataset of 45 kidneys (18 normal and 27 diseased kidneys diagnosed with hydronephrosis) through the leave-one-out cross validation method. Quantitative results show the proposed detection method could extract the kidney position, orientation, and scale ratio with root mean square values of 1.3 +/- 0.9 mm, 6.34 +/- 4.32 degrees, and 1.73 +/- 0.04, respectively. This method could be helpful in automating kidney segmentation for routine clinical evaluation.

Neural electrical activity and neural network growth.

Science.gov (United States)

Gafarov, F M

2018-05-01

The development of central and peripheral neural system depends in part on the emergence of the correct functional connectivity in its input and output pathways. Now it is generally accepted that molecular factors guide neurons to establish a primary scaffold that undergoes activity-dependent refinement for building a fully functional circuit. However, a number of experimental results obtained recently shows that the neuronal electrical activity plays an important role in the establishing of initial interneuronal connections. Nevertheless, these processes are rather difficult to study experimentally, due to the absence of theoretical description and quantitative parameters for estimation of the neuronal activity influence on growth in neural networks. In this work we propose a general framework for a theoretical description of the activity-dependent neural network growth. The theoretical description incorporates a closed-loop growth model in which the neural activity can affect neurite outgrowth, which in turn can affect neural activity. We carried out the detailed quantitative analysis of spatiotemporal activity patterns and studied the relationship between individual cells and the network as a whole to explore the relationship between developing connectivity and activity patterns. The model, developed in this work will allow us to develop new experimental techniques for studying and quantifying the influence of the neuronal activity on growth processes in neural networks and may lead to a novel techniques for constructing large-scale neural networks by self-organization. Copyright © 2018 Elsevier Ltd. All rights reserved.

ProLanGO: Protein Function Prediction Using Neural Machine Translation Based on a Recurrent Neural Network.

Science.gov (United States)

Cao, Renzhi; Freitas, Colton; Chan, Leong; Sun, Miao; Jiang, Haiqing; Chen, Zhangxin

2017-10-17

With the development of next generation sequencing techniques, it is fast and cheap to determine protein sequences but relatively slow and expensive to extract useful information from protein sequences because of limitations of traditional biological experimental techniques. Protein function prediction has been a long standing challenge to fill the gap between the huge amount of protein sequences and the known function. In this paper, we propose a novel method to convert the protein function problem into a language translation problem by the new proposed protein sequence language "ProLan" to the protein function language "GOLan", and build a neural machine translation model based on recurrent neural networks to translate "ProLan" language to "GOLan" language. We blindly tested our method by attending the latest third Critical Assessment of Function Annotation (CAFA 3) in 2016, and also evaluate the performance of our methods on selected proteins whose function was released after CAFA competition. The good performance on the training and testing datasets demonstrates that our new proposed method is a promising direction for protein function prediction. In summary, we first time propose a method which converts the protein function prediction problem to a language translation problem and applies a neural machine translation model for protein function prediction.

Proposal of a model of mammalian neural induction

Science.gov (United States)

Levine, Ariel J.; Brivanlou, Ali H.

2009-01-01

How does the vertebrate embryo make a nervous system? This complex question has been at the center of developmental biology for many years. The earliest step in this process – the induction of neural tissue – is intimately linked to patterning of the entire early embryo, and the molecular and embryological basis these processes are beginning to emerge. Here, we analyze classic and cutting-edge findings on neural induction in the mouse. We find that data from genetics, tissue explants, tissue grafting, and molecular marker expression support a coherent framework for mammalian neural induction. In this model, the gastrula organizer of the mouse embryo inhibits BMP signaling to allow neural tissue to form as a default fate – in the absence of instructive signals. The first neural tissue induced is anterior and subsequent neural tissue is posteriorized to form the midbrain, hindbrain, and spinal cord. The anterior visceral endoderm protects the pre-specified anterior neural fate from similar posteriorization, allowing formation of forebrain. This model is very similar to the default model of neural induction in the frog, thus bridging the evolutionary gap between amphibians and mammals. PMID:17585896

Neural tube defects in Waardenburg syndrome: A case report and review of the literature.

Science.gov (United States)

Hart, Joseph; Miriyala, Kalpana

2017-09-01

Waardenburg syndrome type 1 (WS1) is an autosomal dominant genetic condition characterized by sensorineural deafness and pigment abnormalities, and is caused by variants in the PAX3 homeodomain. PAX3 variants have been associated with severe neural tube defects in mice and humans, but the frequency and clinical manifestations of this symptom remain largely unexplored in humans. Consequently, the role of PAX3 in human neural tube formation remains a study of interest, for clinical as well as research purposes. Though the association between spina bifida and WS1 is now well-documented, no study has attempted to characterize the range of spina bifida phenotypes seen in WS. Spina bifida encompasses several diagnoses with a wide scope of clinical severity, ranging from spina bifida occulta to myelomeningocele. We present a patient with Waardenburg syndrome type 1 caused by a novel missense variant in PAX3, presenting with myelomeningocele, Arnold-Chiari malformation, and hydrocephalus at birth. Additionally, we review 32 total cases of neural tube defects associated with WS. Including this report, there have been 15 published cases of myelomeningocele, 10 cases of unspecified spina bifida, 3 cases of sacral dimples, 0 cases of meningocele, and 4 cases of miscellaneous other neural tube defects. Though the true frequency of each phenotype cannot be determined from this collection of cases, these results demonstrate that Waardenburg syndrome type 1 carries a notable risk of severe neural tube defects, which has implications in prenatal and genetic counseling. © 2017 Wiley Periodicals, Inc.

Implantable neurotechnologies: a review of integrated circuit neural amplifiers.

Science.gov (United States)

Ng, Kian Ann; Greenwald, Elliot; Xu, Yong Ping; Thakor, Nitish V

2016-01-01

Neural signal recording is critical in modern day neuroscience research and emerging neural prosthesis programs. Neural recording requires the use of precise, low-noise amplifier systems to acquire and condition the weak neural signals that are transduced through electrode interfaces. Neural amplifiers and amplifier-based systems are available commercially or can be designed in-house and fabricated using integrated circuit (IC) technologies, resulting in very large-scale integration or application-specific integrated circuit solutions. IC-based neural amplifiers are now used to acquire untethered/portable neural recordings, as they meet the requirements of a miniaturized form factor, light weight and low power consumption. Furthermore, such miniaturized and low-power IC neural amplifiers are now being used in emerging implantable neural prosthesis technologies. This review focuses on neural amplifier-based devices and is presented in two interrelated parts. First, neural signal recording is reviewed, and practical challenges are highlighted. Current amplifier designs with increased functionality and performance and without penalties in chip size and power are featured. Second, applications of IC-based neural amplifiers in basic science experiments (e.g., cortical studies using animal models), neural prostheses (e.g., brain/nerve machine interfaces) and treatment of neuronal diseases (e.g., DBS for treatment of epilepsy) are highlighted. The review concludes with future outlooks of this technology and important challenges with regard to neural signal amplification.

Analysis of Al2O3—parylene C bilayer coatings and impact of microelectrode topography on long term stability of implantable neural arrays

Science.gov (United States)

Caldwell, Ryan; Mandal, Himadri; Sharma, Rohit; Solzbacher, Florian; Tathireddy, Prashant; Rieth, Loren

2017-08-01

Objective. Performance of many dielectric coatings for neural electrodes degrades over time, contributing to loss of neural signals and evoked percepts. Studies using planar test substrates have found that a novel bilayer coating of atomic-layer deposited (ALD) Al2O3 and parylene C is a promising candidate for neural electrode applications, exhibiting superior stability to parylene C alone. However, initial results from bilayer encapsulation testing on non-planar devices have been less positive. Our aim was to evaluate ALD Al2O3-parylene C coatings using novel test paradigms, to rigorously evaluate dielectric coatings for neural electrode applications by incorporating neural electrode topography into test structure design. Approach. Five test devices incorporated three distinct topographical features common to neural electrodes, derived from the utah electrode array (UEA). Devices with bilayer (52 nm Al2O3  +  6 µm parylene C) were evaluated against parylene C controls (N  ⩾  6 per device type). Devices were aged in phosphate buffered saline at 67 °C for up to 311 d, and monitored through: (1) leakage current to evaluate encapsulation lifetimes (>1 nA during 5VDC bias indicated failure), and (2) wideband (1-105 Hz) impedance. Main results. Mean-times-to-failure (MTTFs) ranged from 12 to 506 d for bilayer-coated devices, versus 10 to  >2310 d for controls. Statistical testing (log-rank test, α  =  0.05) of failure rates gave mixed results but favored the control condition. After failure, impedance loss for bilayer devices continued for months and manifested across the entire spectrum, whereas the effect was self-limiting after several days, and restricted to frequencies  physiological fluids may improve performance. Testing frameworks which take neural electrode complexities into account will be well suited to reliably evaluate such encapsulation schemes.

Microfluidic engineered high cell density three-dimensional neural cultures

Science.gov (United States)

Cullen, D. Kacy; Vukasinovic, Jelena; Glezer, Ari; La Placa, Michelle C.

2007-06-01

Three-dimensional (3D) neural cultures with cells distributed throughout a thick, bioactive protein scaffold may better represent neurobiological phenomena than planar correlates lacking matrix support. Neural cells in vivo interact within a complex, multicellular environment with tightly coupled 3D cell-cell/cell-matrix interactions; however, thick 3D neural cultures at cell densities approaching that of brain rapidly decay, presumably due to diffusion limited interstitial mass transport. To address this issue, we have developed a novel perfusion platform that utilizes forced intercellular convection to enhance mass transport. First, we demonstrated that in thick (>500 µm) 3D neural cultures supported by passive diffusion, cell densities =104 cells mm-3), continuous medium perfusion at 2.0-11.0 µL min-1 improved viability compared to non-perfused cultures (p death and matrix degradation. In perfused cultures, survival was dependent on proximity to the perfusion source at 2.00-6.25 µL min-1 (p 90% viability in both neuronal cultures and neuronal-astrocytic co-cultures. This work demonstrates the utility of forced interstitial convection in improving the survival of high cell density 3D engineered neural constructs and may aid in the development of novel tissue-engineered systems reconstituting 3D cell-cell/cell-matrix interactions.

Application of neural network technology to setpoint control of a simulated reactor experiment loop

International Nuclear Information System (INIS)

Cordes, G.A.; Bryan, S.R.; Powell, R.H.; Chick, D.R.

1991-01-01

This paper describes the design, implementation, and application of artificial neural networks to achieve temperature and flow rate control for a simulation of a typical experiment loop in the Advanced Test Reactor (ATR) located at the Idaho National Engineering Laboratory (INEL). The goal of the project was to research multivariate, nonlinear control using neural networks. A loop simulation code was adapted for the project and used to create a training set and test the neural network controller for comparison with the existing loop controllers. The results for the best neural network design are documented and compared with existing loop controller action. The neural network was shown to be as accurate at loop control as the classical controllers in the operating region represented by the training set. 5 refs., 8 figs., 3 tabs

Artificial neural networks a practical course

CERN Document Server

da Silva, Ivan Nunes; Andrade Flauzino, Rogerio; Liboni, Luisa Helena Bartocci; dos Reis Alves, Silas Franco

2017-01-01

This book provides comprehensive coverage of neural networks, their evolution, their structure, the problems they can solve, and their applications. The first half of the book looks at theoretical investigations on artificial neural networks and addresses the key architectures that are capable of implementation in various application scenarios. The second half is designed specifically for the production of solutions using artificial neural networks to solve practical problems arising from different areas of knowledge. It also describes the various implementation details that were taken into account to achieve the reported results. These aspects contribute to the maturation and improvement of experimental techniques to specify the neural network architecture that is most appropriate for a particular application scope. The book is appropriate for students in graduate and upper undergraduate courses in addition to researchers and professionals.

Evolvable synthetic neural system

Science.gov (United States)

Curtis, Steven A. (Inventor)

2009-01-01

An evolvable synthetic neural system includes an evolvable neural interface operably coupled to at least one neural basis function. Each neural basis function includes an evolvable neural interface operably coupled to a heuristic neural system to perform high-level functions and an autonomic neural system to perform low-level functions. In some embodiments, the evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy.

Pharmacokinetics, Biodistribution, and Toxicity Evaluation of Anti-SEMA3A (F11) in In Vivo Models.

Science.gov (United States)

Lee, Jaehyun; Kim, Donggeon; Son, Eunju; Yoo, Su-Ji; Sa, Jason K; Shin, Yong Jae; Yoon, Yeup; Nam, DO-Hyun

2018-05-01

The aim of our study was to investigate the pharmacokinetics (PK), tissue distribution and toxicity of F11 antibody to semaphorin 3A in mouse models and explore its anti-angiogenic and tumor-inhibitory effect. Patient-derived xenograft (PDX) models were established via subcutaneous implantation of glioblastoma multiforme (GBM) cells and treated with F11. F11 significantly attenuated tumor growth and angiogenesis in the GBM PDX model. Within the range of administered doses, the PK of F11 in serum demonstrated a linear fashion, consistent with general PK profiles of soluble antigen-targeting antibodies. Additionally, the clearance level was detected at between 4.63 and 7.12 ml/d/kg, while the biological half-life was measured at 6.9 and 9.4 days. Tissue distribution of F11 in kidney, liver and heart was consistent with previously reported antibody patterns. However, the presence of F11 in the brain was an interesting finding. Collectively, our results revealed angiogenic and tumor-inhibitory effect of F11 antibody and its potential therapeutic use within a clinical framework based on PK, biodistribution and toxicity evaluation in mouse models. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Neural neworks in a management information systems

Directory of Open Access Journals (Sweden)

Jana Weinlichová

2009-01-01

Full Text Available For having retrospection for all over the data which are used, analyzed, evaluated and for a future incident predictions are used Management Information Systems and Business Intelligence. In case of not to be able to apply standard methods of data processing there can be with benefit applied an Artificial Intelligence. In this article will be referred to proofed abilities of Neural Networks. The Neural Networks is supported by many software products related to provide effective solution of manager issues. Those products are given as primary support for manager issues solving. We were tried to find reciprocally between products using Neural Networks and between Management Information Systems for finding a real possibility of applying Neural Networks as a direct part of Management Information Systems (MIS. In the article are presented possibilities to apply Neural Networks on different types of tasks in MIS.

Isointense infant brain MRI segmentation with a dilated convolutional neural network

OpenAIRE

Moeskops, Pim; Pluim, Josien P. W.

2017-01-01

Quantitative analysis of brain MRI at the age of 6 months is difficult because of the limited contrast between white matter and gray matter. In this study, we use a dilated triplanar convolutional neural network in combination with a non-dilated 3D convolutional neural network for the segmentation of white matter, gray matter and cerebrospinal fluid in infant brain MR images, as provided by the MICCAI grand challenge on 6-month infant brain MRI segmentation.

Ship Detection in Gaofen-3 SAR Images Based on Sea Clutter Distribution Analysis and Deep Convolutional Neural Network.

Science.gov (United States)

An, Quanzhi; Pan, Zongxu; You, Hongjian

2018-01-24

Target detection is one of the important applications in the field of remote sensing. The Gaofen-3 (GF-3) Synthetic Aperture Radar (SAR) satellite launched by China is a powerful tool for maritime monitoring. This work aims at detecting ships in GF-3 SAR images using a new land masking strategy, the appropriate model for sea clutter and a neural network as the discrimination scheme. Firstly, the fully convolutional network (FCN) is applied to separate the sea from the land. Then, by analyzing the sea clutter distribution in GF-3 SAR images, we choose the probability distribution model of Constant False Alarm Rate (CFAR) detector from K-distribution, Gamma distribution and Rayleigh distribution based on a tradeoff between the sea clutter modeling accuracy and the computational complexity. Furthermore, in order to better implement CFAR detection, we also use truncated statistic (TS) as a preprocessing scheme and iterative censoring scheme (ICS) for boosting the performance of detector. Finally, we employ a neural network to re-examine the results as the discrimination stage. Experiment results on three GF-3 SAR images verify the effectiveness and efficiency of this approach.

Neural complexity: A graph theoretic interpretation

Science.gov (United States)

Barnett, L.; Buckley, C. L.; Bullock, S.

2011-04-01

One of the central challenges facing modern neuroscience is to explain the ability of the nervous system to coherently integrate information across distinct functional modules in the absence of a central executive. To this end, Tononi [Proc. Natl. Acad. Sci. USA.PNASA60027-842410.1073/pnas.91.11.5033 91, 5033 (1994)] proposed a measure of neural complexity that purports to capture this property based on mutual information between complementary subsets of a system. Neural complexity, so defined, is one of a family of information theoretic metrics developed to measure the balance between the segregation and integration of a system’s dynamics. One key question arising for such measures involves understanding how they are influenced by network topology. Sporns [Cereb. Cortex53OPAV1047-321110.1093/cercor/10.2.127 10, 127 (2000)] employed numerical models in order to determine the dependence of neural complexity on the topological features of a network. However, a complete picture has yet to be established. While De Lucia [Phys. Rev. EPLEEE81539-375510.1103/PhysRevE.71.016114 71, 016114 (2005)] made the first attempts at an analytical account of this relationship, their work utilized a formulation of neural complexity that, we argue, did not reflect the intuitions of the original work. In this paper we start by describing weighted connection matrices formed by applying a random continuous weight distribution to binary adjacency matrices. This allows us to derive an approximation for neural complexity in terms of the moments of the weight distribution and elementary graph motifs. In particular, we explicitly establish a dependency of neural complexity on cyclic graph motifs.

Podocalyxin Is a Novel Polysialylated Neural Adhesion Protein with Multiple Roles in Neural Development and Synapse Formation

Science.gov (United States)

Vitureira, Nathalia; Andrés, Rosa; Pérez-Martínez, Esther; Martínez, Albert; Bribián, Ana; Blasi, Juan; Chelliah, Shierley; López-Doménech, Guillermo; De Castro, Fernando; Burgaya, Ferran; McNagny, Kelly; Soriano, Eduardo

2010-01-01

Neural development and plasticity are regulated by neural adhesion proteins, including the polysialylated form of NCAM (PSA-NCAM). Podocalyxin (PC) is a renal PSA-containing protein that has been reported to function as an anti-adhesin in kidney podocytes. Here we show that PC is widely expressed in neurons during neural development. Neural PC interacts with the ERM protein family, and with NHERF1/2 and RhoA/G. Experiments in vitro and phenotypic analyses of podxl-deficient mice indicate that PC is involved in neurite growth, branching and axonal fasciculation, and that PC loss-of-function reduces the number of synapses in the CNS and in the neuromuscular system. We also show that whereas some of the brain PC functions require PSA, others depend on PC per se. Our results show that PC, the second highly sialylated neural adhesion protein, plays multiple roles in neural development. PMID:20706633

"Geo-statistics methods and neural networks in geophysical applications: A case study"

Science.gov (United States)

Rodriguez Sandoval, R.; Urrutia Fucugauchi, J.; Ramirez Cruz, L. C.

2008-12-01

The study is focus in the Ebano-Panuco basin of northeastern Mexico, which is being explored for hydrocarbon reservoirs. These reservoirs are in limestones and there is interest in determining porosity and permeability in the carbonate sequences. The porosity maps presented in this study are estimated from application of multiattribute and neural networks techniques, which combine geophysics logs and 3-D seismic data by means of statistical relationships. The multiattribute analysis is a process to predict a volume of any underground petrophysical measurement from well-log and seismic data. The data consist of a series of target logs from wells which tie a 3-D seismic volume. The target logs are neutron porosity logs. From the 3-D seismic volume a series of sample attributes is calculated. The objective of this study is to derive a set of attributes and the target log values. The selected set is determined by a process of forward stepwise regression. The analysis can be linear or nonlinear. In the linear mode the method consists of a series of weights derived by least-square minimization. In the nonlinear mode, a neural network is trained using the select attributes as inputs. In this case we used a probabilistic neural network PNN. The method is applied to a real data set from PEMEX. For better reservoir characterization the porosity distribution was estimated using both techniques. The case shown a continues improvement in the prediction of the porosity from the multiattribute to the neural network analysis. The improvement is in the training and the validation, which are important indicators of the reliability of the results. The neural network showed an improvement in resolution over the multiattribute analysis. The final maps provide more realistic results of the porosity distribution.

Inversion of a lateral log using neural networks

International Nuclear Information System (INIS)

Garcia, G.; Whitman, W.W.

1992-01-01

In this paper a technique using neural networks is demonstrated for the inversion of a lateral log. The lateral log is simulated by a finite difference method which in turn is used as an input to a backpropagation neural network. An initial guess earth model is generated from the neural network, which is then input to a Marquardt inversion. The neural network reacts to gross and subtle data features in actual logs and produces a response inferred from the knowledge stored in the network during a training process. The neural network inversion of lateral logs is tested on synthetic and field data. Tests using field data resulted in a final earth model whose simulated lateral is in good agreement with the actual log data

A fuzzy neural network for sensor signal estimation

International Nuclear Information System (INIS)

Na, Man Gyun

2000-01-01

In this work, a fuzzy neural network is used to estimate the relevant sensor signal using other sensor signals. Noise components in input signals into the fuzzy neural network are removed through the wavelet denoising technique. Principal component analysis (PCA) is used to reduce the dimension of an input space without losing a significant amount of information. A lower dimensional input space will also usually reduce the time necessary to train a fuzzy-neural network. Also, the principal component analysis makes easy the selection of the input signals into the fuzzy neural network. The fuzzy neural network parameters are optimized by two learning methods. A genetic algorithm is used to optimize the antecedent parameters of the fuzzy neural network and a least-squares algorithm is used to solve the consequent parameters. The proposed algorithm was verified through the application to the pressurizer water level and the hot-leg flowrate measurements in pressurized water reactors

The equilibrium of neural firing: A mathematical theory

Energy Technology Data Exchange (ETDEWEB)

Lan, Sizhong, E-mail: lsz@fuyunresearch.org [Fuyun Research, Beijing, 100055 (China)

2014-12-15

Inspired by statistical thermodynamics, we presume that neuron system has equilibrium condition with respect to neural firing. We show that, even with dynamically changeable neural connections, it is inevitable for neural firing to evolve to equilibrium. To study the dynamics between neural firing and neural connections, we propose an extended communication system where noisy channel has the tendency towards fixed point, implying that neural connections are always attracted into fixed points such that equilibrium can be reached. The extended communication system and its mathematics could be useful back in thermodynamics.

Mass reconstruction with a neural network

International Nuclear Information System (INIS)

Loennblad, L.; Peterson, C.; Roegnvaldsson, T.

1992-01-01

A feed-forward neural network method is developed for reconstructing the invariant mass of hadronic jets appearing in a calorimeter. The approach is illustrated in W→qanti q, where W-bosons are produced in panti p reactions at SPS collider energies. The neural network method yields results that are superior to conventional methods. This neural network application differs from the classification ones in the sense that an analog number (the mass) is computed by the network, rather than a binary decision being made. As a by-product our application clearly demonstrates the need for using 'intelligent' variables in instances when the amount of training instances is limited. (orig.)

Enhancement of digital radiography image quality using a convolutional neural network.

Science.gov (United States)

Sun, Yuewen; Li, Litao; Cong, Peng; Wang, Zhentao; Guo, Xiaojing

2017-01-01

Digital radiography system is widely used for noninvasive security check and medical imaging examination. However, the system has a limitation of lower image quality in spatial resolution and signal to noise ratio. In this study, we explored whether the image quality acquired by the digital radiography system can be improved with a modified convolutional neural network to generate high-resolution images with reduced noise from the original low-quality images. The experiment evaluated on a test dataset, which contains 5 X-ray images, showed that the proposed method outperformed the traditional methods (i.e., bicubic interpolation and 3D block-matching approach) as measured by peak signal to noise ratio (PSNR) about 1.3 dB while kept highly efficient processing time within one second. Experimental results demonstrated that a residual to residual (RTR) convolutional neural network remarkably improved the image quality of object structural details by increasing the image resolution and reducing image noise. Thus, this study indicated that applying this RTR convolutional neural network system was useful to improve image quality acquired by the digital radiography system.

Conserved gene regulatory module specifies lateral neural borders across bilaterians.

Science.gov (United States)

Li, Yongbin; Zhao, Di; Horie, Takeo; Chen, Geng; Bao, Hongcun; Chen, Siyu; Liu, Weihong; Horie, Ryoko; Liang, Tao; Dong, Biyu; Feng, Qianqian; Tao, Qinghua; Liu, Xiao

2017-08-01

The lateral neural plate border (NPB), the neural part of the vertebrate neural border, is composed of central nervous system (CNS) progenitors and peripheral nervous system (PNS) progenitors. In invertebrates, PNS progenitors are also juxtaposed to the lateral boundary of the CNS. Whether there are conserved molecular mechanisms determining vertebrate and invertebrate lateral neural borders remains unclear. Using single-cell-resolution gene-expression profiling and genetic analysis, we present evidence that orthologs of the NPB specification module specify the invertebrate lateral neural border, which is composed of CNS and PNS progenitors. First, like in vertebrates, the conserved neuroectoderm lateral border specifier Msx/vab-15 specifies lateral neuroblasts in Caenorhabditis elegans Second, orthologs of the vertebrate NPB specification module ( Msx/vab-15 , Pax3/7/pax-3 , and Zic/ref-2 ) are significantly enriched in worm lateral neuroblasts. In addition, like in other bilaterians, the expression domain of Msx/vab-15 is more lateral than those of Pax3/7/pax-3 and Zic/ref- 2 in C. elegans Third, we show that Msx/vab-15 regulates the development of mechanosensory neurons derived from lateral neural progenitors in multiple invertebrate species, including C. elegans , Drosophila melanogaster , and Ciona intestinalis We also identify a novel lateral neural border specifier, ZNF703/tlp-1 , which functions synergistically with Msx/vab- 15 in both C. elegans and Xenopus laevis These data suggest a common origin of the molecular mechanism specifying lateral neural borders across bilaterians.

Boolean Factor Analysis by Attractor Neural Network

Czech Academy of Sciences Publication Activity Database

Frolov, A. A.; Húsek, Dušan; Muraviev, I. P.; Polyakov, P.Y.

2007-01-01

Roč. 18, č. 3 (2007), s. 698-707 ISSN 1045-9227 R&D Projects: GA AV ČR 1ET100300419; GA ČR GA201/05/0079 Institutional research plan: CEZ:AV0Z10300504 Keywords : recurrent neural network * Hopfield-like neural network * associative memory * unsupervised learning * neural network architecture * neural network application * statistics * Boolean factor analysis * dimensionality reduction * features clustering * concepts search * information retrieval Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.769, year: 2007

The quest for a Quantum Neural Network

OpenAIRE

Schuld, M.; Sinayskiy, I.; Petruccione, F.

2014-01-01

With the overwhelming success in the field of quantum information in the last decades, the "quest" for a Quantum Neural Network (QNN) model began in order to combine quantum computing with the striking properties of neural computing. This article presents a systematic approach to QNN research, which so far consists of a conglomeration of ideas and proposals. It outlines the challenge of combining the nonlinear, dissipative dynamics of neural computing and the linear, unitary dynamics of quant...

Morphological neural networks

Energy Technology Data Exchange (ETDEWEB)

Ritter, G.X.; Sussner, P. [Univ. of Florida, Gainesville, FL (United States)

1996-12-31

The theory of artificial neural networks has been successfully applied to a wide variety of pattern recognition problems. In this theory, the first step in computing the next state of a neuron or in performing the next layer neural network computation involves the linear operation of multiplying neural values by their synaptic strengths and adding the results. Thresholding usually follows the linear operation in order to provide for nonlinearity of the network. In this paper we introduce a novel class of neural networks, called morphological neural networks, in which the operations of multiplication and addition are replaced by addition and maximum (or minimum), respectively. By taking the maximum (or minimum) of sums instead of the sum of products, morphological network computation is nonlinear before thresholding. As a consequence, the properties of morphological neural networks are drastically different than those of traditional neural network models. In this paper we consider some of these differences and provide some particular examples of morphological neural network.

Effects of Fish Oil Supplementation during the Suckling Period on Auditory Neural Conduction in n-3 Fatty Acid-Deficient Rat Pups

Directory of Open Access Journals (Sweden)

vida rahimi

2014-07-01

Full Text Available Abstract Introduction: Omega 3 fatty acid especially in the form of fish oil, has structural and biological role in the body's various systems especially nervous system. Numerous studies have tried to research about it. Auditory is one of the affected systems. Omega 3 deficiency can have devastating effects on the nervous system and auditory. This study aimed to evaluate neural conduction in n-3 fatty acid-deficient rat pups following the supplementation of fish oil consumption during the suckling period Materials and Methods: In this interventional and experimental study, one sources of omega3 fatty acid (fish oil were fed to rat pups of n-3 PUFA-deficient dams to compare changes in their auditory neural conduction with that of control and n-3 PUFA-deficient groups, using Auditory Brainstem Response (ABR. The parameters of interest were P1, P3, P4 absolute latency, P1-P3, P1-P4 and P3-P4 IPL , P4/P1 amplitude ratio . The rat pups were given oral fish oil, 5 Ml /g weight for 17 days, between the age of 5 and 21 days. Results There were no significant group differences in P1 and P3 absolute latency (p > 0.05. but the result in P4 was significant(P ≤ 0.05 . The n-3 PUFA deficient +vehicle had the most prolonged (the worst P1-P4 IPL and P3-P4 IPL compared with control and n-3 PUFA deficient + FO groups. There was no significant difference in P1-P4 IPL and P3-P4 IPL between n-3 PUFA deficient + FO and control groups (p > 0.05.There was a significant effect of diet on P1-P4 IPL and P3-P4 IPL between groups (P ≤ 0.05. Conclusion: The results of present study showed the effect of omega3 deficiency on auditory neural structure during pregnancy and lactation period. Additionally, we observed the reduced devastating effects on neural conduction in n-3 fatty acid-deficient rat pups following the supplementation of fish oil during the suckling period

Neural growth into a microchannel network: towards a regenerative neural interface

NARCIS (Netherlands)

Wieringa, P.A.; Wiertz, Remy; le Feber, Jakob; Rutten, Wim

2009-01-01

We propose and validated a design for a highly selective 'endcap' regenerative neural interface towards a neuroprosthesis. In vitro studies using rat cortical neurons determine if a branching microchannel structure can counter fasciculated growth and cause neurites to separte from one another,

Neural networks and applications tutorial

Science.gov (United States)

Guyon, I.

1991-09-01

The importance of neural networks has grown dramatically during this decade. While only a few years ago they were primarily of academic interest, now dozens of companies and many universities are investigating the potential use of these systems and products are beginning to appear. The idea of building a machine whose architecture is inspired by that of the brain has roots which go far back in history. Nowadays, technological advances of computers and the availability of custom integrated circuits, permit simulations of hundreds or even thousands of neurons. In conjunction, the growing interest in learning machines, non-linear dynamics and parallel computation spurred renewed attention in artificial neural networks. Many tentative applications have been proposed, including decision systems (associative memories, classifiers, data compressors and optimizers), or parametric models for signal processing purposes (system identification, automatic control, noise canceling, etc.). While they do not always outperform standard methods, neural network approaches are already used in some real world applications for pattern recognition and signal processing tasks. The tutorial is divided into six lectures, that where presented at the Third Graduate Summer Course on Computational Physics (September 3-7, 1990) on Parallel Architectures and Applications, organized by the European Physical Society: (1) Introduction: machine learning and biological computation. (2) Adaptive artificial neurons (perceptron, ADALINE, sigmoid units, etc.): learning rules and implementations. (3) Neural network systems: architectures, learning algorithms. (4) Applications: pattern recognition, signal processing, etc. (5) Elements of learning theory: how to build networks which generalize. (6) A case study: a neural network for on-line recognition of handwritten alphanumeric characters.

Neural principles of memory and a neural theory of analogical insight

Science.gov (United States)

Lawson, David I.; Lawson, Anton E.

1993-12-01

Grossberg's principles of neural modeling are reviewed and extended to provide a neural level theory to explain how analogies greatly increase the rate of learning and can, in fact, make learning and retention possible. In terms of memory, the key point is that the mind is able to recognize and recall when it is able to match sensory input from new objects, events, or situations with past memory records of similar objects, events, or situations. When a match occurs, an adaptive resonance is set up in which the synaptic strengths of neurons are increased; thus a long term record of the new input is formed in memory. Systems of neurons called outstars and instars are presumably the underlying units that enable this to occur. Analogies can greatly facilitate learning and retention because they activate the outstars (i.e., the cells that are sampling the to-be-learned pattern) and cause the neural activity to grow exponentially by forming feedback loops. This increased activity insures the boost in synaptic strengths of neurons, thus causing storage and retention in long-term memory (i.e., learning).

Neural Based Orthogonal Data Fitting The EXIN Neural Networks

CERN Document Server

Cirrincione, Giansalvo

2008-01-01

Written by three leaders in the field of neural based algorithms, Neural Based Orthogonal Data Fitting proposes several neural networks, all endowed with a complete theory which not only explains their behavior, but also compares them with the existing neural and traditional algorithms. The algorithms are studied from different points of view, including: as a differential geometry problem, as a dynamic problem, as a stochastic problem, and as a numerical problem. All algorithms have also been analyzed on real time problems (large dimensional data matrices) and have shown accurate solutions. Wh

A Neural Network-Based Interval Pattern Matcher

Directory of Open Access Journals (Sweden)

Jing Lu

2015-07-01

Full Text Available One of the most important roles in the machine learning area is to classify, and neural networks are very important classifiers. However, traditional neural networks cannot identify intervals, let alone classify them. To improve their identification ability, we propose a neural network-based interval matcher in our paper. After summarizing the theoretical construction of the model, we take a simple and a practical weather forecasting experiment, which show that the recognizer accuracy reaches 100% and that is promising.

A fully implantable rodent neural stimulator

Science.gov (United States)

Perry, D. W. J.; Grayden, D. B.; Shepherd, R. K.; Fallon, J. B.

2012-02-01

The ability to electrically stimulate neural and other excitable tissues in behaving experimental animals is invaluable for both the development of neural prostheses and basic neurological research. We developed a fully implantable neural stimulator that is able to deliver two channels of intra-cochlear electrical stimulation in the rat. It is powered via a novel omni-directional inductive link and includes an on-board microcontroller with integrated radio link, programmable current sources and switching circuitry to generate charge-balanced biphasic stimulation. We tested the implant in vivo and were able to elicit both neural and behavioural responses. The implants continued to function for up to five months in vivo. While targeted to cochlear stimulation, with appropriate electrode arrays the stimulator is well suited to stimulating other neurons within the peripheral or central nervous systems. Moreover, it includes significant on-board data acquisition and processing capabilities, which could potentially make it a useful platform for telemetry applications, where there is a need to chronically monitor physiological variables in unrestrained animals.

Inverting radiometric measurements with a neural network

Science.gov (United States)

Measure, Edward M.; Yee, Young P.; Balding, Jeff M.; Watkins, Wendell R.

1992-02-01

A neural network scheme for retrieving remotely sensed vertical temperature profiles was applied to observed ground based radiometer measurements. The neural network used microwave radiance measurements and surface measurements of temperature and pressure as inputs. Because the microwave radiometer is capable of measuring 4 oxygen channels at 5 different elevation angles (9, 15, 25, 40, and 90 degs), 20 microwave measurements are potentially available. Because these measurements have considerable redundancy, a neural network was experimented with, accepting as inputs microwave measurements taken at 53.88 GHz, 40 deg; 57.45 GHz, 40 deg; and 57.45, 90 deg. The primary test site was located at White Sands Missile Range (WSMR), NM. Results are compared with measurements made simultaneously with balloon borne radiosonde instruments and with radiometric temperature retrievals made using more conventional retrieval algorithms. The neural network was trained using a Widrow-Hoff delta rule procedure. Functions of date to include season dependence in the retrieval process and functions of time to include diurnal effects were used as inputs to the neural network.

Hippocalcin Is Required for Astrocytic Differentiation through Activation of Stat3 in Hippocampal Neural Precursor Cells.

Directory of Open Access Journals (Sweden)

Min-Jeong Kang

2016-10-01

Full Text Available Hippocalcin (Hpca is a neuronal calcium sensor protein expressed in the mammalian brain. However, its function in neural stem/precursor cells has not yet been studied. Here, we clarify the function of Hpca in astrocytic differentiation in hippocampal neural precursor cells (HNPCs. When we overexpressed Hpca in HNPCs in the presence or absence of bFGF, expression levels of nerve-growth factors such as neurotrophin-3 (NT-3, neurotrophin-4/5 (NT-4/5 and brain-derived neurotrophic factor (BDNF, together with the proneural basic helix loop helix (bHLH transcription factors neuroD and neurogenin 1 (ngn1, increased significantly. In addition, there was an increase in the number of cells expressing glial fibrillary acidic protein (GFAP, an astrocyte marker, and in dendrite outgrowth, indicating astrocytic differentiation of the HNPCs. Downregulation of Hpca by transfection with Hpca siRNA reduced expression of NT-3, NT-4/5, BDNF, neuroD and ngn1 as well as levels of GFAP protein. Furthermore, overexpression of Hpca increased the phosphorylation of STAT3 (Ser727, and this effect was abolished by treatment with a STAT3 inhibitor (S3I-201, suggesting that STAT3 (Ser727 activation is involved in Hpca-mediated astrocytic differentiation. As expected, treatment with Stat3 siRNA or STAT3 inhibitor caused a complete inhibition of astrogliogenesis induced by Hpca overexpression. Taken together, this is the first report to show that Hpca, acting through Stat3, has an important role in the expression of neurotrophins and proneural bHLH transcription factors, and that it is an essential regulator of astrocytic differentiation and dendrite outgrowth in HNPCs.

Neural network and its application to CT imaging

Energy Technology Data Exchange (ETDEWEB)

Nikravesh, M.; Kovscek, A.R.; Patzek, T.W. [Lawrence Berkeley National Lab., CA (United States)] [and others

1997-02-01

We present an integrated approach to imaging the progress of air displacement by spontaneous imbibition of oil into sandstone. We combine Computerized Tomography (CT) scanning and neural network image processing. The main aspects of our approach are (I) visualization of the distribution of oil and air saturation by CT, (II) interpretation of CT scans using neural networks, and (III) reconstruction of 3-D images of oil saturation from the CT scans with a neural network model. Excellent agreement between the actual images and the neural network predictions is found.

Classification of brain MRI with big data and deep 3D convolutional neural networks

Science.gov (United States)

Wegmayr, Viktor; Aitharaju, Sai; Buhmann, Joachim

2018-02-01

Our ever-aging society faces the growing problem of neurodegenerative diseases, in particular dementia. Magnetic Resonance Imaging provides a unique tool for non-invasive investigation of these brain diseases. However, it is extremely difficult for neurologists to identify complex disease patterns from large amounts of three-dimensional images. In contrast, machine learning excels at automatic pattern recognition from large amounts of data. In particular, deep learning has achieved impressive results in image classification. Unfortunately, its application to medical image classification remains difficult. We consider two reasons for this difficulty: First, volumetric medical image data is considerably scarcer than natural images. Second, the complexity of 3D medical images is much higher compared to common 2D images. To address the problem of small data set size, we assemble the largest dataset ever used for training a deep 3D convolutional neural network to classify brain images as healthy (HC), mild cognitive impairment (MCI) or Alzheimers disease (AD). We use more than 20.000 images from subjects of these three classes, which is almost 9x the size of the previously largest data set. The problem of high dimensionality is addressed by using a deep 3D convolutional neural network, which is state-of-the-art in large-scale image classification. We exploit its ability to process the images directly, only with standard preprocessing, but without the need for elaborate feature engineering. Compared to other work, our workflow is considerably simpler, which increases clinical applicability. Accuracy is measured on the ADNI+AIBL data sets, and the independent CADDementia benchmark.

Modular representation of layered neural networks.

Science.gov (United States)

Watanabe, Chihiro; Hiramatsu, Kaoru; Kashino, Kunio

2018-01-01

Layered neural networks have greatly improved the performance of various applications including image processing, speech recognition, natural language processing, and bioinformatics. However, it is still difficult to discover or interpret knowledge from the inference provided by a layered neural network, since its internal representation has many nonlinear and complex parameters embedded in hierarchical layers. Therefore, it becomes important to establish a new methodology by which layered neural networks can be understood. In this paper, we propose a new method for extracting a global and simplified structure from a layered neural network. Based on network analysis, the proposed method detects communities or clusters of units with similar connection patterns. We show its effectiveness by applying it to three use cases. (1) Network decomposition: it can decompose a trained neural network into multiple small independent networks thus dividing the problem and reducing the computation time. (2) Training assessment: the appropriateness of a trained result with a given hyperparameter or randomly chosen initial parameters can be evaluated by using a modularity index. And (3) data analysis: in practical data it reveals the community structure in the input, hidden, and output layers, which serves as a clue for discovering knowledge from a trained neural network. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pax7 lineage contributions to the mammalian neural crest.

Directory of Open Access Journals (Sweden)

Barbara Murdoch

Full Text Available Neural crest cells are vertebrate-specific multipotent cells that contribute to a variety of tissues including the peripheral nervous system, melanocytes, and craniofacial bones and cartilage. Abnormal development of the neural crest is associated with several human maladies including cleft/lip palate, aggressive cancers such as melanoma and neuroblastoma, and rare syndromes, like Waardenburg syndrome, a complex disorder involving hearing loss and pigment defects. We previously identified the transcription factor Pax7 as an early marker, and required component for neural crest development in chick embryos. In mammals, Pax7 is also thought to play a role in neural crest development, yet the precise contribution of Pax7 progenitors to the neural crest lineage has not been determined.Here we use Cre/loxP technology in double transgenic mice to fate map the Pax7 lineage in neural crest derivates. We find that Pax7 descendants contribute to multiple tissues including the cranial, cardiac and trunk neural crest, which in the cranial cartilage form a distinct regional pattern. The Pax7 lineage, like the Pax3 lineage, is additionally detected in some non-neural crest tissues, including a subset of the epithelial cells in specific organs.These results demonstrate a previously unappreciated widespread distribution of Pax7 descendants within and beyond the neural crest. They shed light regarding the regionally distinct phenotypes observed in Pax3 and Pax7 mutants, and provide a unique perspective into the potential roles of Pax7 during disease and development.

Neural Differentiation of Human Adipose Tissue-Derived Stem Cells Involves Activation of the Wnt5a/JNK Signalling

Directory of Open Access Journals (Sweden)

Sujeong Jang

2015-01-01

Full Text Available Stem cells are a powerful resource for cell-based transplantation therapies, but understanding of stem cell differentiation at the molecular level is not clear yet. We hypothesized that the Wnt pathway controls stem cell maintenance and neural differentiation. We have characterized the transcriptional expression of Wnt during the neural differentiation of hADSCs. After neural induction, the expressions of Wnt2, Wnt4, and Wnt11 were decreased, but the expression of Wnt5a was increased compared with primary hADSCs in RT-PCR analysis. In addition, the expression levels of most Fzds and LRP5/6 ligand were decreased, but not Fzd3 and Fzd5. Furthermore, Dvl1 and RYK expression levels were downregulated in NI-hADSCs. There were no changes in the expression of ß-catenin and GSK3ß. Interestingly, Wnt5a expression was highly increased in NI-hADSCs by real time RT-PCR analysis and western blot. Wnt5a level was upregulated after neural differentiation and Wnt3, Dvl2, and Naked1 levels were downregulated. Finally, we found that the JNK expression was increased after neural induction and ERK level was decreased. Thus, this study shows for the first time how a single Wnt5a ligand can activate the neural differentiation pathway through the activation of Wnt5a/JNK pathway by binding Fzd3 and Fzd5 and directing Axin/GSK-3ß in hADSCs.

Evaluating the Causal Link Between Malaria Infection and Endemic Burkitt Lymphoma in Northern Uganda: A Mendelian Randomization Study.

Science.gov (United States)

Legason, Ismail D; Pfeiffer, Ruth M; Udquim, Krizia-Ivana; Bergen, Andrew W; Gouveia, Mateus H; Kirimunda, Samuel; Otim, Isaac; Karlins, Eric; Kerchan, Patrick; Nabalende, Hadijah; Bayanjargal, Ariunaa; Emmanuel, Benjamin; Kagwa, Paul; Talisuna, Ambrose O; Bhatia, Kishor; Yeager, Meredith; Biggar, Robert J; Ayers, Leona W; Reynolds, Steven J; Goedert, James J; Ogwang, Martin D; Fraumeni, Joseph F; Prokunina-Olsson, Ludmila; Mbulaiteye, Sam M

2017-11-01

Plasmodium falciparum (Pf) malaria infection is suspected to cause endemic Burkitt Lymphoma (eBL), but the evidence remains unsettled. An inverse relationship between sickle cell trait (SCT) and eBL, which supports that between malaria and eBL, has been reported before, but in small studies with low power. We investigated this hypothesis in children in a population-based study in northern Uganda using Mendelian Randomization. Malaria-related polymorphisms (SCT, IL10, IL1A, CD36, SEMA3C, and IFNAR1) were genotyped in 202 eBL cases and 624 controls enrolled during 2010-2015. We modeled associations between genotypes and eBL or malaria using logistic regression. SCT was associated with decreased risk of eBL (adjusted odds ratio [OR] 0·37, 95% CI 0·21-0·66; p=0·0003). Decreased risk of eBL was associated with IL10 rs1800896-CT (OR 0·73, 95% CI 0·50-1·07) and -CC genotypes (OR 0·53, 95% CI 0·29-0·95, p trend =0·019); IL1A rs2856838-AG (OR 0·56, 95% CI 0·39-0·81) and -AA genotype (OR 0·50, 95% CI 0·28-1·01, p trend =0·0016); and SEMA3C rs4461841-CT or -CC genotypes (OR 0·57, 95% CI 0·35-0·93, p=0·0193). SCT and IL10 rs1800896, IL1A rs2856838, but not SEMA3C rs4461841, polymorphisms were associated with decreased risk of malaria in the controls. Our results support a causal effect of malaria infection on eBL. Published by Elsevier B.V.

3-D inversion of borehole-to-surface electrical data using a back-propagation neural network

Science.gov (United States)

Ho, Trong Long

2009-08-01

The "fluid-flow tomography", an advanced technique for geoelectrical survey based on the conventional mise-à-la-masse measurement, has been developed by Exploration Geophysics Laboratory at the Kyushu University. This technique is proposed to monitor fluid-flow behavior during water injection and production in a geothermal field. However data processing of this technique is very costly. In this light, this paper will discuss the solution to cost reduction by applying a neural network in the data processing. A case study in the Takigami geothermal field in Japan will be used to illustrate this. The achieved neural network in this case study is three-layered and feed-forward. The most successful learning algorithm in this network is the Resilient Propagation (RPROP). Consequently, the study advances the pragmatism of the "fluid-flow tomography" technique which can be widely used for geothermal fields. Accuracy of the solution is then verified by using root mean square (RMS) misfit error as an indicator.

Development of a neural network technique for KSTAR Thomson scattering diagnostics

Energy Technology Data Exchange (ETDEWEB)

Lee, Seung Hun, E-mail: leesh81@nfri.re.kr; Lee, J. H. [National Fusion Research Institute, 169-148 Gwahak-ro, Yuseong-gu, Daejeon 34133 (Korea, Republic of); Yamada, I. [National Institute Fusion Science, Toki, Gifu 509-5292 (Japan); Park, Jae Sun [Department of Physics, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of)

2016-11-15

Neural networks provide powerful approaches of dealing with nonlinear data and have been successfully applied to fusion plasma diagnostics and control systems. Controlling tokamak plasmas in real time is essential to measure the plasma parameters in situ. However, the χ{sup 2} method traditionally used in Thomson scattering diagnostics hampers real-time measurement due to the complexity of the calculations involved. In this study, we applied a neural network approach to Thomson scattering diagnostics in order to calculate the electron temperature, comparing the results to those obtained with the χ{sup 2} method. The best results were obtained for 10{sup 3} training cycles and eight nodes in the hidden layer. Our neural network approach shows good agreement with the χ{sup 2} method and performs the calculation twenty times faster.

Results from a MA16-based neural trigger in an experiment looking for beauty

International Nuclear Information System (INIS)

Baldanza, C.; Beichter, J.; Bisi, F.; Bruels, N.; Bruschini, C.; Cotta-Ramusino, A.; D'Antone, I.; Malferrari, L.; Mazzanti, P.; Musico, P.; Novelli, P.; Odorici, F.; Odorico, R.; Passaseo, M.; Zuffa, M.

1996-01-01

Results from a neural-network trigger based on the digital MA16 chip of Siemens are reported. The neural trigger has been applied to data from the WA92 experiment, looking for beauty particles, which have been collected during a run in which a neural trigger module based on Intel's analog neural chip ETANN operated, as already reported. The MA16 board hosting the chip has a 16-bit I/O precision and a 53-bit precision for internal calculations. It operated at 50 MHz, yielding a response time for a 16 input-variable net of 3 μs for a Fisher discriminant (1-layer net) and of 6 μs for a 2-layer net. Results are compared with those previously obtained with the ETANN trigger. (orig.)

Results from a MA16-based neural trigger in an experiment looking for beauty

Energy Technology Data Exchange (ETDEWEB)

Baldanza, C. [Istituto Nazionale di Fisica Nucleare, Bologna (Italy); Beichter, J. [Siemens AG, ZFE T ME2, 81730 Munich (Germany); Bisi, F. [Istituto Nazionale di Fisica Nucleare, Bologna (Italy); Bruels, N. [Siemens AG, ZFE T ME2, 81730 Munich (Germany); Bruschini, C. [INFN/Genoa, Via Dodecaneso 33, 16146 Genoa (Italy); Cotta-Ramusino, A. [Istituto Nazionale di Fisica Nucleare, Bologna (Italy); D`Antone, I. [Istituto Nazionale di Fisica Nucleare, Bologna (Italy); Malferrari, L. [Istituto Nazionale di Fisica Nucleare, Bologna (Italy); Mazzanti, P. [Istituto Nazionale di Fisica Nucleare, Bologna (Italy); Musico, P. [INFN/Genoa, Via Dodecaneso 33, 16146 Genoa (Italy); Novelli, P. [INFN/Genoa, Via Dodecaneso 33, 16146 Genoa (Italy); Odorici, F. [Istituto Nazionale di Fisica Nucleare, Bologna (Italy); Odorico, R. [Istituto Nazionale di Fisica Nucleare, Bologna (Italy); Passaseo, M. [CERN, 1211 Geneva 23 (Switzerland); Zuffa, M. [Istituto Nazionale di Fisica Nucleare, Bologna (Italy)

1996-07-11

Results from a neural-network trigger based on the digital MA16 chip of Siemens are reported. The neural trigger has been applied to data from the WA92 experiment, looking for beauty particles, which have been collected during a run in which a neural trigger module based on Intel`s analog neural chip ETANN operated, as already reported. The MA16 board hosting the chip has a 16-bit I/O precision and a 53-bit precision for internal calculations. It operated at 50 MHz, yielding a response time for a 16 input-variable net of 3 {mu}s for a Fisher discriminant (1-layer net) and of 6 {mu}s for a 2-layer net. Results are compared with those previously obtained with the ETANN trigger. (orig.).

A Possible Neural Representation of Mathematical Group Structures.

Science.gov (United States)

Pomi, Andrés

2016-09-01

Every cognitive activity has a neural representation in the brain. When humans deal with abstract mathematical structures, for instance finite groups, certain patterns of activity are occurring in the brain that constitute their neural representation. A formal neurocognitive theory must account for all the activities developed by our brain and provide a possible neural representation for them. Associative memories are neural network models that have a good chance of achieving a universal representation of cognitive phenomena. In this work, we present a possible neural representation of mathematical group structures based on associative memory models that store finite groups through their Cayley graphs. A context-dependent associative memory stores the transitions between elements of the group when multiplied by each generator of a given presentation of the group. Under a convenient election of the vector basis mapping the elements of the group in the neural activity, the input of a vector corresponding to a generator of the group collapses the context-dependent rectangular matrix into a virtual square permutation matrix that is the matrix representation of the generator. This neural representation corresponds to the regular representation of the group, in which to each element is assigned a permutation matrix. This action of the generator on the memory matrix can also be seen as the dissection of the corresponding monochromatic subgraph of the Cayley graph of the group, and the adjacency matrix of this subgraph is the permutation matrix corresponding to the generator.

A TLD dose algorithm using artificial neural networks

International Nuclear Information System (INIS)

Moscovitch, M.; Rotunda, J.E.; Tawil, R.A.; Rathbone, B.A.

1995-01-01

An artificial neural network was designed and used to develop a dose algorithm for a multi-element thermoluminescence dosimeter (TLD). The neural network architecture is based on the concept of functional links network (FLN). Neural network is an information processing method inspired by the biological nervous system. A dose algorithm based on neural networks is fundamentally different as compared to conventional algorithms, as it has the capability to learn from its own experience. The neural network algorithm is shown the expected dose values (output) associated with given responses of a multi-element dosimeter (input) many times. The algorithm, being trained that way, eventually is capable to produce its own unique solution to similar (but not exactly the same) dose calculation problems. For personal dosimetry, the output consists of the desired dose components: deep dose, shallow dose and eye dose. The input consists of the TL data obtained from the readout of a multi-element dosimeter. The neural network approach was applied to the Harshaw Type 8825 TLD, and was shown to significantly improve the performance of this dosimeter, well within the U.S. accreditation requirements for personnel dosimeters

Neural activation in stress-related exhaustion

DEFF Research Database (Denmark)

Gavelin, Hanna Malmberg; Neely, Anna Stigsdotter; Andersson, Micael

2017-01-01

The primary purpose of this study was to investigate the association between burnout and neural activation during working memory processing in patients with stress-related exhaustion. Additionally, we investigated the neural effects of cognitive training as part of stress rehabilitation. Fifty...... association between burnout level and working memory performance was found, however, our findings indicate that frontostriatal neural responses related to working memory were modulated by burnout severity. We suggest that patients with high levels of burnout need to recruit additional cognitive resources...... to uphold task performance. Following cognitive training, increased neural activation was observed during 3-back in working memory-related regions, including the striatum, however, low sample size limits any firm conclusions....

A Neural Marker for Social Bias Toward In-group Accents.

Science.gov (United States)

Bestelmeyer, Patricia E G; Belin, Pascal; Ladd, D Robert

2015-10-01

Accents provide information about the speaker's geographical, socio-economic, and ethnic background. Research in applied psychology and sociolinguistics suggests that we generally prefer our own accent to other varieties of our native language and attribute more positive traits to it. Despite the widespread influence of accents on social interactions, educational and work settings the neural underpinnings of this social bias toward our own accent and, what may drive this bias, are unexplored. We measured brain activity while participants from two different geographical backgrounds listened passively to 3 English accent types embedded in an adaptation design. Cerebral activity in several regions, including bilateral amygdalae, revealed a significant interaction between the participants' own accent and the accent they listened to: while repetition of own accents elicited an enhanced neural response, repetition of the other group's accent resulted in reduced responses classically associated with adaptation. Our findings suggest that increased social relevance of, or greater emotional sensitivity to in-group accents, may underlie the own-accent bias. Our results provide a neural marker for the bias associated with accents, and show, for the first time, that the neural response to speech is partly shaped by the geographical background of the listener. © The Author 2014. Published by Oxford University Press.

Towards a magnetoresistive platform for neural signal recording

Science.gov (United States)

Sharma, P. P.; Gervasoni, G.; Albisetti, E.; D'Ercoli, F.; Monticelli, M.; Moretti, D.; Forte, N.; Rocchi, A.; Ferrari, G.; Baldelli, P.; Sampietro, M.; Benfenati, F.; Bertacco, R.; Petti, D.

2017-05-01

A promising strategy to get deeper insight on brain functionalities relies on the investigation of neural activities at the cellular and sub-cellular level. In this framework, methods for recording neuron electrical activity have gained interest over the years. Main technological challenges are associated to finding highly sensitive detection schemes, providing considerable spatial and temporal resolution. Moreover, the possibility to perform non-invasive assays would constitute a noteworthy benefit. In this work, we present a magnetoresistive platform for the detection of the action potential propagation in neural cells. Such platform allows, in perspective, the in vitro recording of neural signals arising from single neurons, neural networks and brain slices.

Intelligent neural network diagnostic system

International Nuclear Information System (INIS)

Mohamed, A.H.

2010-01-01

Recently, artificial neural network (ANN) has made a significant mark in the domain of diagnostic applications. Neural networks are used to implement complex non-linear mappings (functions) using simple elementary units interrelated through connections with adaptive weights. The performance of the ANN is mainly depending on their topology structure and weights. Some systems have been developed using genetic algorithm (GA) to optimize the topology of the ANN. But, they suffer from some limitations. They are : (1) The computation time requires for training the ANN several time reaching for the average weight required, (2) Slowness of GA for optimization process and (3) Fitness noise appeared in the optimization of ANN. This research suggests new issues to overcome these limitations for finding optimal neural network architectures to learn particular problems. This proposed methodology is used to develop a diagnostic neural network system. It has been applied for a 600 MW turbo-generator as a case of real complex systems. The proposed system has proved its significant performance compared to two common methods used in the diagnostic applications.

Development of a Compact Gamma-ray Detector for a Neural-Network Radiation Monitoring

Energy Technology Data Exchange (ETDEWEB)

Kim, H. S.; Ha, J. H.; Lee, K. H. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Lee, C. H. [Hanyang Univ., Seoul (Korea, Republic of)

2012-03-15

Radiation monitoring is very important to secure safety in nuclear-related facilities and against nuclear terrorism. For wide range of radiation monitoring, neutral network system of radiation detection is most efficient way. Thus, a compact radiation detector is useful to install in wide range to be concerned. A compact gamma-ray detector was fabricated by using a CsI(Tl) scintillator, which was matched with the formerly developed PIN photodiode, for a neural network radiation monitoring. At room temperature, the fabricated compact gamma-ray detector demonstrates an energy resolution of 13.3 % for 662 keV 6.9% for 1330 keV. The compactness, the low-voltage power consumption and the physical hardness are very useful features for a neural network radiation monitoring. In this study, characteristics of a fabricated compact gamma-ray detector were presented. An important aspect to consider in a neural-network radiation monitoring such as reaction probability of the fabricated compact detector for angle of incident gamma-ray was also addressed.

Formation of Neural Networks in 3D Scaffolds Fabricated by Means of Laser Microstereolithography.

Science.gov (United States)

Vedunova, M V; Timashev, P S; Mishchenko, T A; Mitroshina, E V; Koroleva, A V; Chichkov, B N; Panchenko, V Ya; Bagratashvili, V N; Mukhina, I V

2016-08-01

We developed and tested new 3D scaffolds for neurotransplantation. Scaffolds of predetermined architectonic were prepared using microstereolithography technique. Scaffolds were highly biocompatible with the nervous tissue cells. In vitro studies showed that the material of fabricated scaffolds is not toxic for dissociated brain cells and promotes the formation of functional neural networks in the matrix. These results demonstrate the possibility of fabrication of tissue-engineering constructs for neurotransplantation based on created scaffolds.

A high-speed analog neural processor

NARCIS (Netherlands)

Masa, P.; Masa, Peter; Hoen, Klaas; Hoen, Klaas; Wallinga, Hans

1994-01-01

Targeted at high-energy physics research applications, our special-purpose analog neural processor can classify up to 70 dimensional vectors within 50 nanoseconds. The decision-making process of the implemented feedforward neural network enables this type of computation to tolerate weight

Neural control of magnetic suspension systems

Science.gov (United States)

Gray, W. Steven

1993-01-01

The purpose of this research program is to design, build and test (in cooperation with NASA personnel from the NASA Langley Research Center) neural controllers for two different small air-gap magnetic suspension systems. The general objective of the program is to study neural network architectures for the purpose of control in an experimental setting and to demonstrate the feasibility of the concept. The specific objectives of the research program are: (1) to demonstrate through simulation and experimentation the feasibility of using neural controllers to stabilize a nonlinear magnetic suspension system; (2) to investigate through simulation and experimentation the performance of neural controllers designs under various types of parametric and nonparametric uncertainty; (3) to investigate through simulation and experimentation various types of neural architectures for real-time control with respect to performance and complexity; and (4) to benchmark in an experimental setting the performance of neural controllers against other types of existing linear and nonlinear compensator designs. To date, the first one-dimensional, small air-gap magnetic suspension system has been built, tested and delivered to the NASA Langley Research Center. The device is currently being stabilized with a digital linear phase-lead controller. The neural controller hardware is under construction. Two different neural network paradigms are under consideration, one based on hidden layer feedforward networks trained via back propagation and one based on using Gaussian radial basis functions trained by analytical methods related to stability conditions. Some advanced nonlinear control algorithms using feedback linearization and sliding mode control are in simulation studies.

Differential effects of erythropoietin on neural and cognitive measures of executive function 3 and 7 days post-administration

DEFF Research Database (Denmark)

Miskowiak, Kamilla; Inkster, Becky; O'Sullivan, Ursula

2008-01-01

Erythropoietin (Epo) has neuroprotective and neurotrophic effects and improves cognitive function in animal models of neurodegenerative and neuropsychiatric illness. In humans, weekly Epo administration over 3 months improves cognitive function in schizophrenia. The neural underpinnings and time...

The Drosophila Neurally Altered Carbohydrate Mutant Has a Defective Golgi GDP-fucose Transporter*

Science.gov (United States)

Geisler, Christoph; Kotu, Varshika; Sharrow, Mary; Rendić, Dubravko; Pöltl, Gerald; Tiemeyer, Michael; Wilson, Iain B. H.; Jarvis, Donald L.

2012-01-01

Studying genetic disorders in model organisms can provide insights into heritable human diseases. The Drosophila neurally altered carbohydrate (nac) mutant is deficient for neural expression of the HRP epitope, which consists of N-glycans with core α1,3-linked fucose residues. Here, we show that a conserved serine residue in the Golgi GDP-fucose transporter (GFR) is substituted by leucine in nac1 flies, which abolishes GDP-fucose transport in vivo and in vitro. This loss of function is due to a biochemical defect, not to destabilization or mistargeting of the mutant GFR protein. Mass spectrometry and HPLC analysis showed that nac1 mutants lack not only core α1,3-linked, but also core α1,6-linked fucose residues on their N-glycans. Thus, the nac1 Gfr mutation produces a previously unrecognized general defect in N-glycan core fucosylation. Transgenic expression of a wild-type Gfr gene restored the HRP epitope in neural tissues, directly demonstrating that the Gfr mutation is solely responsible for the neural HRP epitope deficiency in the nac1 mutant. These results validate the Drosophila nac1 mutant as a model for the human congenital disorder of glycosylation, CDG-IIc (also known as LAD-II), which is also the result of a GFR deficiency. PMID:22745127

Kontrol Kecepatan Motor Induksi menggunakan Algoritma Backpropagation Neural Network

Directory of Open Access Journals (Sweden)

MUHAMMAD RUSWANDI DJALAL

2017-07-01

Full Text Available ABSTRAKBanyak strategi kontrol berbasis kecerdasan buatan telah diusulkan dalam penelitian seperti Fuzzy Logic dan Artificial Neural Network (ANN. Tujuan dari penelitian ini adalah untuk mendesain sebuah kontrol agar kecepatan motor induksi dapat diatur sesuai kebutuhan serta membandingkan kinerja motor induksi tanpa kontrol dan dengan kontrol. Dalam penelitian ini diusulkan sebuah metode artificial neural network untuk mengontrol kecepatan motor induksi tiga fasa. Kecepatan referensi motor diatur pada kecepatan 140 rad/s, 150 rad/s, dan 130 rad/s. Perubahan kecepatan diatur pada setiap interval 0.3 detik dan waktu simulasi maksimum adalah 0,9 detik. Kasus 1 tanpa kontrol, menunjukkan respon torka dan kecepatan dari motor induksi tiga fasa tanpa kontrol. Meskipun kecepatan motor induksi tiga fasa diatur berubah pada setiap 0,3 detik tidak akan mempengaruhi torka. Selain itu, motor induksi tiga fasa tanpa kontrol memiliki kinerja yang buruk dikarenakan kecepatan motor induksi tidak dapat diatur sesuai dengan kebutuhan. Kasus 2 dengan control backpropagation neural network, meskipun kecepatan motor induksi tiga fasa berubah pada setiap 0.3 detik tidak akan mempengaruhi torsi. Selain itu, kontrol backpropagation neural network memiliki kinerja yang baik dikarenakan kecepatan motor induksi dapat diatur sesuai dengan kebutuhan.Kata kunci: Backpropagation Neural Network (BPNN, NN Training, NN Testing, Motor.ABSTRACTMany artificial intelligence-based control strategies have been proposed in research such as Fuzzy Logic and Artificial Neural Network (ANN. The purpose of this research was design a control for the induction motor speed that could be adjusted as needed and compare the performance of induction motor without control and with control. In this research, it was proposed an artificial neural network method to control the speed of three-phase induction motors. The reference speed of motor was set at the rate of 140 rad / s, 150 rad / s, and 130

A Chip for an Implantable Neural Stimulator

DEFF Research Database (Denmark)

Gudnason, Gunnar; Bruun, Erik; Haugland, Morten

2000-01-01

This paper describes a chip for a multichannel neural stimulator for functional electrical stimulation (FES). The purpose of FES is to restore muscular control in disabled patients. The chip performs all the signal processing required in an implanted neural stimulator. The power and digital data...

A wirelessly powered microspectrometer for neural probe-pin device

Science.gov (United States)

Choi, Sang H.; Kim, Min H.; Song, Kyo D.; Yoon, Hargsoon; Lee, Uhn

2015-12-01

Treatment of neurological anomalies, whether done invasively or not, places stringent demands on device functionality and size. We have developed a micro-spectrometer for use as an implantable neural probe to monitor neuro-chemistry in synapses. The micro-spectrometer, based on a NASA-invented miniature Fresnel grating, is capable of differentiating the emission spectra from various brain tissues. The micro-spectrometer meets the size requirements, and is able to probe the neuro-chemistry and suppression voltage typically associated with a neural anomaly. This neural probe-pin device (PPD) is equipped with wireless power technology (WPT) to enable operation in a continuous manner without requiring an implanted battery. The implanted neural PPD, together with a neural electronics interface and WPT, enable real-time measurement and control/feedback for remediation of neural anomalies. The design and performance of the combined PPD/WPT device for monitoring dopamine in a rat brain will be presented to demonstrate the current level of development. Future work on this device will involve the addition of an embedded expert system capable of performing semi-autonomous management of neural functions through a routine of sensing, processing, and control.

Neural networks within multi-core optic fibers.

Science.gov (United States)

Cohen, Eyal; Malka, Dror; Shemer, Amir; Shahmoon, Asaf; Zalevsky, Zeev; London, Michael

2016-07-07

Hardware implementation of artificial neural networks facilitates real-time parallel processing of massive data sets. Optical neural networks offer low-volume 3D connectivity together with large bandwidth and minimal heat production in contrast to electronic implementation. Here, we present a conceptual design for in-fiber optical neural networks. Neurons and synapses are realized as individual silica cores in a multi-core fiber. Optical signals are transferred transversely between cores by means of optical coupling. Pump driven amplification in erbium-doped cores mimics synaptic interactions. We simulated three-layered feed-forward neural networks and explored their capabilities. Simulations suggest that networks can differentiate between given inputs depending on specific configurations of amplification; this implies classification and learning capabilities. Finally, we tested experimentally our basic neuronal elements using fibers, couplers, and amplifiers, and demonstrated that this configuration implements a neuron-like function. Therefore, devices similar to our proposed multi-core fiber could potentially serve as building blocks for future large-scale small-volume optical artificial neural networks.

3D Convolutional Neural Networks for Crop Classification with Multi-Temporal Remote Sensing Images

Directory of Open Access Journals (Sweden)

Shunping Ji

2018-01-01

Full Text Available This study describes a novel three-dimensional (3D convolutional neural networks (CNN based method that automatically classifies crops from spatio-temporal remote sensing images. First, 3D kernel is designed according to the structure of multi-spectral multi-temporal remote sensing data. Secondly, the 3D CNN framework with fine-tuned parameters is designed for training 3D crop samples and learning spatio-temporal discriminative representations, with the full crop growth cycles being preserved. In addition, we introduce an active learning strategy to the CNN model to improve labelling accuracy up to a required threshold with the most efficiency. Finally, experiments are carried out to test the advantage of the 3D CNN, in comparison to the two-dimensional (2D CNN and other conventional methods. Our experiments show that the 3D CNN is especially suitable in characterizing the dynamics of crop growth and outperformed the other mainstream methods.

Insights into function of PSI domains from structure of the Met receptor PSI domain

International Nuclear Information System (INIS)

Kozlov, Guennadi; Perreault, Audrey; Schrag, Joseph D.; Park, Morag; Cygler, Miroslaw; Gehring, Kalle; Ekiel, Irena

2004-01-01

PSI domains are cysteine-rich modules found in extracellular fragments of hundreds of signaling proteins, including plexins, semaphorins, integrins, and attractins. Here, we report the solution structure of the PSI domain from the human Met receptor, a receptor tyrosine kinase critical for proliferation, motility, and differentiation. The structure represents a cysteine knot with short regions of secondary structure including a three-stranded antiparallel β-sheet and two α-helices. All eight cysteines are involved in disulfide bonds with the pattern consistent with that for the PSI domain from Sema4D. Comparison with the Sema4D structure identifies a structurally conserved core comprising the N-terminal half of the PSI domain. Interestingly, this part links adjacent SEMA and immunoglobulin domains in the Sema4D structure, suggesting that the PSI domain serves as a wedge between propeller and immunoglobulin domains and is responsible for the correct positioning of the ligand-binding site of the receptor

Ovariectomy and subsequent treatment with estrogen receptor agonists tune the innate immune system of the hippocampus in middle-aged female rats.

Directory of Open Access Journals (Sweden)

Miklós Sárvári

Full Text Available The innate immune system including microglia has a major contribution to maintenance of the physiological functions of the hippocampus by permanent monitoring of the neural milieu and elimination of tissue-damaging threats. The hippocampus is vulnerable to age-related changes ranging from gene expression to network connectivity. The risk of hippocampal deterioration increases with the decline of gonadal hormone supply. To explore the impact of hormone milieu on the function of the innate immune system in middle-aged female rats, we compared mRNA expression in the hippocampus after gonadal hormone withdrawal, with or without subsequent estrogen replacement using estradiol and isotype-selective estrogen receptor (ER agonists. Targeted profiling assessed the status of the innate immune system (macrophage-associated receptors, complement, inhibitory neuronal ligands, local estradiol synthesis (P450 aromatase and estrogen reception (ER. Results established upregulation of macrophage-associated (Cd45, Iba1, Cd68, Cd11b, Cd18, Fcgr1a, Fcgr2b and complement (C3, factor B, properdin genes in response to ovariectomy. Ovariectomy upregulated Cd22 and downregulated semaphorin3A (Sema3a expression, indicating altered neuronal regulation of microglia. Ovariectomy also led to downregulation of aromatase and upregulation of ERα gene. Of note, analogous changes were observed in the hippocampus of postmenopausal women. In ovariectomized rats, estradiol replacement attenuated Iba1, Cd11b, Fcgr1a, C3, increased mannose receptor Mrc1, Cd163 and reversed Sema3a expression. In contrast, reduced expression of aromatase was not reversed by estradiol. While the effects of ERα agonist closely resembled those of estradiol, ERβ agonist was also capable of attenuating the expression of several macrophage-associated and complement genes. These data together indicate that the innate immune system of the aging hippocampus is highly responsive to the gonadal hormone milieu

A neural network approach to burst detection.

Science.gov (United States)

Mounce, S R; Day, A J; Wood, A S; Khan, A; Widdop, P D; Machell, J

2002-01-01

This paper describes how hydraulic and water quality data from a distribution network may be used to provide a more efficient leakage management capability for the water industry. The research presented concerns the application of artificial neural networks to the issue of detection and location of leakage in treated water distribution systems. An architecture for an Artificial Neural Network (ANN) based system is outlined. The neural network uses time series data produced by sensors to directly construct an empirical model for predication and classification of leaks. Results are presented using data from an experimental site in Yorkshire Water's Keighley distribution system.

Neural networks

International Nuclear Information System (INIS)

Denby, Bruce; Lindsey, Clark; Lyons, Louis

1992-01-01

The 1980s saw a tremendous renewal of interest in 'neural' information processing systems, or 'artificial neural networks', among computer scientists and computational biologists studying cognition. Since then, the growth of interest in neural networks in high energy physics, fueled by the need for new information processing technologies for the next generation of high energy proton colliders, can only be described as explosive

A quantum-implementable neural network model

Science.gov (United States)

Chen, Jialin; Wang, Lingli; Charbon, Edoardo

2017-10-01

A quantum-implementable neural network, namely quantum probability neural network (QPNN) model, is proposed in this paper. QPNN can use quantum parallelism to trace all possible network states to improve the result. Due to its unique quantum nature, this model is robust to several quantum noises under certain conditions, which can be efficiently implemented by the qubus quantum computer. Another advantage is that QPNN can be used as memory to retrieve the most relevant data and even to generate new data. The MATLAB experimental results of Iris data classification and MNIST handwriting recognition show that much less neuron resources are required in QPNN to obtain a good result than the classical feedforward neural network. The proposed QPNN model indicates that quantum effects are useful for real-life classification tasks.

A Universal 3D Voxel Descriptor for Solid-State Material Informatics with Deep Convolutional Neural Networks.

Science.gov (United States)

Kajita, Seiji; Ohba, Nobuko; Jinnouchi, Ryosuke; Asahi, Ryoji

2017-12-05

Material informatics (MI) is a promising approach to liberate us from the time-consuming Edisonian (trial and error) process for material discoveries, driven by machine-learning algorithms. Several descriptors, which are encoded material features to feed computers, were proposed in the last few decades. Especially to solid systems, however, their insufficient representations of three dimensionality of field quantities such as electron distributions and local potentials have critically hindered broad and practical successes of the solid-state MI. We develop a simple, generic 3D voxel descriptor that compacts any field quantities, in such a suitable way to implement convolutional neural networks (CNNs). We examine the 3D voxel descriptor encoded from the electron distribution by a regression test with 680 oxides data. The present scheme outperforms other existing descriptors in the prediction of Hartree energies that are significantly relevant to the long-wavelength distribution of the valence electrons. The results indicate that this scheme can forecast any functionals of field quantities just by learning sufficient amount of data, if there is an explicit correlation between the target properties and field quantities. This 3D descriptor opens a way to import prominent CNNs-based algorithms of supervised, semi-supervised and reinforcement learnings into the solid-state MI.

Evolvable Neural Software System

Science.gov (United States)

Curtis, Steven A.

2009-01-01

The Evolvable Neural Software System (ENSS) is composed of sets of Neural Basis Functions (NBFs), which can be totally autonomously created and removed according to the changing needs and requirements of the software system. The resulting structure is both hierarchical and self-similar in that a given set of NBFs may have a ruler NBF, which in turn communicates with other sets of NBFs. These sets of NBFs may function as nodes to a ruler node, which are also NBF constructs. In this manner, the synthetic neural system can exhibit the complexity, three-dimensional connectivity, and adaptability of biological neural systems. An added advantage of ENSS over a natural neural system is its ability to modify its core genetic code in response to environmental changes as reflected in needs and requirements. The neural system is fully adaptive and evolvable and is trainable before release. It continues to rewire itself while on the job. The NBF is a unique, bilevel intelligence neural system composed of a higher-level heuristic neural system (HNS) and a lower-level, autonomic neural system (ANS). Taken together, the HNS and the ANS give each NBF the complete capabilities of a biological neural system to match sensory inputs to actions. Another feature of the NBF is the Evolvable Neural Interface (ENI), which links the HNS and ANS. The ENI solves the interface problem between these two systems by actively adapting and evolving from a primitive initial state (a Neural Thread) to a complicated, operational ENI and successfully adapting to a training sequence of sensory input. This simulates the adaptation of a biological neural system in a developmental phase. Within the greater multi-NBF and multi-node ENSS, self-similar ENI s provide the basis for inter-NBF and inter-node connectivity.

Identifying Emotions on the Basis of Neural Activation.

Science.gov (United States)

Kassam, Karim S; Markey, Amanda R; Cherkassky, Vladimir L; Loewenstein, George; Just, Marcel Adam

2013-01-01

We attempt to determine the discriminability and organization of neural activation corresponding to the experience of specific emotions. Method actors were asked to self-induce nine emotional states (anger, disgust, envy, fear, happiness, lust, pride, sadness, and shame) while in an fMRI scanner. Using a Gaussian Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1) neural activation of the same individual in other trials, 2) neural activation of other individuals who experienced similar trials, and 3) neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing.

Glassy carbon MEMS for novel origami-styled 3D integrated intracortical and epicortical neural probes

Science.gov (United States)

Goshi, Noah; Castagnola, Elisa; Vomero, Maria; Gueli, Calogero; Cea, Claudia; Zucchini, Elena; Bjanes, David; Maggiolini, Emma; Moritz, Chet; Kassegne, Sam; Ricci, Davide; Fadiga, Luciano

2018-06-01

We report on a novel technology for microfabricating 3D origami-styled micro electro-mechanical systems (MEMS) structures with glassy carbon (GC) features and a supporting polymer substrate. GC MEMS devices that open to form 3D microstructures are microfabricated from GC patterns that are made through pyrolysis of polymer precursors on high-temperature resisting substrates like silicon or quartz and then transferring the patterned devices to a flexible substrate like polyimide followed by deposition of an insulation layer. The devices on flexible substrate are then folded into 3D form in an origami-fashion. These 3D MEMS devices have tunable mechanical properties that are achieved by selectively varying the thickness of the polymeric substrate and insulation layers at any desired location. This technology opens new possibilities by enabling microfabrication of a variety of 3D GC MEMS structures suited to applications ranging from biochemical sensing to implantable microelectrode arrays. As a demonstration of the technology, a neural signal recording microelectrode array platform that integrates both surface (cortical) and depth (intracortical) GC microelectrodes onto a single flexible thin-film device is introduced. When the device is unfurled, a pre-shaped shank of polyimide automatically comes off the substrate and forms the penetrating part of the device in a 3D fashion. With the advantage of being highly reproducible and batch-fabricated, the device introduced here allows for simultaneous recording of electrophysiological signals from both the brain surface (electrocorticography—ECoG) and depth (single neuron). Our device, therefore, has the potential to elucidate the roles of underlying neurons on the different components of µECoG signals. For in vivo validation of the design capabilities, the recording sites are coated with a poly(3,4-ethylenedioxythiophene)—polystyrene sulfonate—carbon nanotube composite, to improve the electrical conductivity of the

A neural network model for credit risk evaluation.

Science.gov (United States)

Khashman, Adnan

2009-08-01

Credit scoring is one of the key analytical techniques in credit risk evaluation which has been an active research area in financial risk management. This paper presents a credit risk evaluation system that uses a neural network model based on the back propagation learning algorithm. We train and implement the neural network to decide whether to approve or reject a credit application, using seven learning schemes and real world credit applications from the Australian credit approval datasets. A comparison of the system performance under the different learning schemes is provided, furthermore, we compare the performance of two neural networks; with one and two hidden layers following the ideal learning scheme. Experimental results suggest that neural networks can be effectively used in automatic processing of credit applications.

Regulation of Msx genes by a Bmp gradient is essential for neural crest specification.

Science.gov (United States)

Tribulo, Celeste; Aybar, Manuel J; Nguyen, Vu H; Mullins, Mary C; Mayor, Roberto

2003-12-01

There is evidence in Xenopus and zebrafish embryos that the neural crest/neural folds are specified at the border of the neural plate by a precise threshold concentration of a Bmp gradient. In order to understand the molecular mechanism by which a gradient of Bmp is able to specify the neural crest, we analyzed how the expression of Bmp targets, the Msx genes, is regulated and the role that Msx genes has in neural crest specification. As Msx genes are directly downstream of Bmp, we analyzed Msx gene expression after experimental modification in the level of Bmp activity by grafting a bead soaked with noggin into Xenopus embryos, by expressing in the ectoderm a dominant-negative Bmp4 or Bmp receptor in Xenopus and zebrafish embryos, and also through Bmp pathway component mutants in the zebrafish. All the results show that a reduction in the level of Bmp activity leads to an increase in the expression of Msx genes in the neural plate border. Interestingly, by reaching different levels of Bmp activity in animal cap ectoderm, we show that a specific concentration of Bmp induces msx1 expression to a level similar to that required to induce neural crest. Our results indicate that an intermediate level of Bmp activity specifies the expression of Msx genes in the neural fold region. In addition, we have analyzed the role that msx1 plays on neural crest specification. As msx1 has a role in dorsoventral pattering, we have carried out conditional gain- and loss-of-function experiments using different msx1 constructs fused to a glucocorticoid receptor element to avoid an early effect of this factor. We show that msx1 expression is able to induce all other early neural crest markers tested (snail, slug, foxd3) at the time of neural crest specification. Furthermore, the expression of a dominant negative of Msx genes leads to the inhibition of all the neural crest markers analyzed. It has been previously shown that snail is one of the earliest genes acting in the neural crest

A Wireless Fully Passive Neural Recording Device for Unobtrusive Neuropotential Monitoring.

Science.gov (United States)

Kiourti, Asimina; Lee, Cedric W L; Chae, Junseok; Volakis, John L

2016-01-01

We propose a novel wireless fully passive neural recording device for unobtrusive neuropotential monitoring. Previous work demonstrated the feasibility of monitoring emulated brain signals in a wireless fully passive manner. In this paper, we propose a novel realistic recorder that is significantly smaller and much more sensitive. The proposed recorder utilizes a highly efficient microwave backscattering method and operates without any formal power supply or regulating elements. Also, no intracranial wires or cables are required. In-vitro testing is performed inside a four-layer head phantom (skin, bone, gray matter, and white matter). Compared to our former implementation, the neural recorder proposed in this study has the following improved features: 1) 59% smaller footprint, 2) up to 20-dB improvement in neuropotential detection sensitivity, and 3) encapsulation in biocompatible polymer. For the first time, temporal emulated neuropotentials as low as 63 μVpp can be detected in a wireless fully passive manner. Remarkably, the high-sensitivity achieved in this study implies reading of most neural signals generated by the human brain. The proposed recorder brings forward transformational possibilities in wireless fully passive neural detection for a very wide range of applications (e.g., epilepsy, Alzheimer's, mental disorders, etc.).

Application of a neural network for reflectance spectrum classification

Science.gov (United States)

Yang, Gefei; Gartley, Michael

2017-05-01

Traditional reflectance spectrum classification algorithms are based on comparing spectrum across the electromagnetic spectrum anywhere from the ultra-violet to the thermal infrared regions. These methods analyze reflectance on a pixel by pixel basis. Inspired by high performance that Convolution Neural Networks (CNN) have demonstrated in image classification, we applied a neural network to analyze directional reflectance pattern images. By using the bidirectional reflectance distribution function (BRDF) data, we can reformulate the 4-dimensional into 2 dimensions, namely incident direction × reflected direction × channels. Meanwhile, RIT's micro-DIRSIG model is utilized to simulate additional training samples for improving the robustness of the neural networks training. Unlike traditional classification by using hand-designed feature extraction with a trainable classifier, neural networks create several layers to learn a feature hierarchy from pixels to classifier and all layers are trained jointly. Hence, the our approach of utilizing the angular features are different to traditional methods utilizing spatial features. Although training processing typically has a large computational cost, simple classifiers work well when subsequently using neural network generated features. Currently, most popular neural networks such as VGG, GoogLeNet and AlexNet are trained based on RGB spatial image data. Our approach aims to build a directional reflectance spectrum based neural network to help us to understand from another perspective. At the end of this paper, we compare the difference among several classifiers and analyze the trade-off among neural networks parameters.

3-D Bioprinting of Neural Tissue for Applications in Cell Therapy and Drug Screening

Directory of Open Access Journals (Sweden)

Michaela Thomas

2017-11-01

Full Text Available Neurodegenerative diseases affect millions of individuals in North America and cost the health-care industry billions of dollars for treatment. Current treatment options for degenerative diseases focus on physical rehabilitation or drug therapies, which temporarily mask the effects of cell damage, but quickly lose their efficacy. Cell therapies for the central nervous system remain an untapped market due to the complexity involved in growing neural tissues, controlling their differentiation, and protecting them from the hostile environment they meet upon implantation. Designing tissue constructs for the discovery of better drug treatments are also limited due to the resolution needed for an accurate cellular representation of the brain, in addition to being expensive and difficult to translate to biocompatible materials. 3-D printing offers a streamlined solution for engineering brain tissue for drug discovery or, in the future, for implantation. New microfluidic and bioplotting devices offer increased resolution, little impact on cell viability and have been tested with several bioink materials including fibrin, collagen, hyaluronic acid, poly(caprolactone, and poly(ethylene glycol. This review details current efforts at bioprinting neural tissue and highlights promising avenues for future work.

Control of autonomous robot using neural networks

Science.gov (United States)

Barton, Adam; Volna, Eva

2017-07-01

The aim of the article is to design a method of control of an autonomous robot using artificial neural networks. The introductory part describes control issues from the perspective of autonomous robot navigation and the current mobile robots controlled by neural networks. The core of the article is the design of the controlling neural network, and generation and filtration of the training set using ART1 (Adaptive Resonance Theory). The outcome of the practical part is an assembled Lego Mindstorms EV3 robot solving the problem of avoiding obstacles in space. To verify models of an autonomous robot behavior, a set of experiments was created as well as evaluation criteria. The speed of each motor was adjusted by the controlling neural network with respect to the situation in which the robot was found.

Generation of Neural Progenitor Spheres from Human Pluripotent Stem Cells in a Suspension Bioreactor.

Science.gov (United States)

Yan, Yuanwei; Song, Liqing; Tsai, Ang-Chen; Ma, Teng; Li, Yan

2016-01-01

Conventional two-dimensional (2-D) culture systems cannot provide large numbers of human pluripotent stem cells (hPSCs) and their derivatives that are demanded for commercial and clinical applications in in vitro drug screening, disease modeling, and potentially cell therapy. The technologies that support three-dimensional (3-D) suspension culture, such as a stirred bioreactor, are generally considered as promising approaches to produce the required cells. Recently, suspension bioreactors have also been used to generate mini-brain-like structure from hPSCs for disease modeling, showing the important role of bioreactor in stem cell culture. This chapter describes a detailed culture protocol for neural commitment of hPSCs into neural progenitor cell (NPC) spheres using a spinner bioreactor. The basic steps to prepare hPSCs for bioreactor inoculation are illustrated from cell thawing to cell propagation. The method for generating NPCs from hPSCs in the spinner bioreactor along with the static control is then described. The protocol in this study can be applied to the generation of NPCs from hPSCs for further neural subtype specification, 3-D neural tissue development, or potential preclinical studies or clinical applications in neurological diseases.

Maintenance of neural progenitor cell stemness in 3D hydrogels requires matrix remodelling

Science.gov (United States)

Madl, Christopher M.; Lesavage, Bauer L.; Dewi, Ruby E.; Dinh, Cong B.; Stowers, Ryan S.; Khariton, Margarita; Lampe, Kyle J.; Nguyen, Duong; Chaudhuri, Ovijit; Enejder, Annika; Heilshorn, Sarah C.

2017-12-01

Neural progenitor cell (NPC) culture within three-dimensional (3D) hydrogels is an attractive strategy for expanding a therapeutically relevant number of stem cells. However, relatively little is known about how 3D material properties such as stiffness and degradability affect the maintenance of NPC stemness in the absence of differentiation factors. Over a physiologically relevant range of stiffness from ~0.5 to 50 kPa, stemness maintenance did not correlate with initial hydrogel stiffness. In contrast, hydrogel degradation was both correlated with, and necessary for, maintenance of NPC stemness. This requirement for degradation was independent of cytoskeletal tension generation and presentation of engineered adhesive ligands, instead relying on matrix remodelling to facilitate cadherin-mediated cell-cell contact and promote β-catenin signalling. In two additional hydrogel systems, permitting NPC-mediated matrix remodelling proved to be a generalizable strategy for stemness maintenance in 3D. Our findings have identified matrix remodelling, in the absence of cytoskeletal tension generation, as a previously unknown strategy to maintain stemness in 3D.

Normalization as a canonical neural computation

Science.gov (United States)

Carandini, Matteo; Heeger, David J.

2012-01-01

There is increasing evidence that the brain relies on a set of canonical neural computations, repeating them across brain regions and modalities to apply similar operations to different problems. A promising candidate for such a computation is normalization, in which the responses of neurons are divided by a common factor that typically includes the summed activity of a pool of neurons. Normalization was developed to explain responses in the primary visual cortex and is now thought to operate throughout the visual system, and in many other sensory modalities and brain regions. Normalization may underlie operations such as the representation of odours, the modulatory effects of visual attention, the encoding of value and the integration of multisensory information. Its presence in such a diversity of neural systems in multiple species, from invertebrates to mammals, suggests that it serves as a canonical neural computation. PMID:22108672

Face recognition: a convolutional neural-network approach.

Science.gov (United States)

Lawrence, S; Giles, C L; Tsoi, A C; Back, A D

1997-01-01

We present a hybrid neural-network for human face recognition which compares favourably with other methods. The system combines local image sampling, a self-organizing map (SOM) neural network, and a convolutional neural network. The SOM provides a quantization of the image samples into a topological space where inputs that are nearby in the original space are also nearby in the output space, thereby providing dimensionality reduction and invariance to minor changes in the image sample, and the convolutional neural network provides partial invariance to translation, rotation, scale, and deformation. The convolutional network extracts successively larger features in a hierarchical set of layers. We present results using the Karhunen-Loeve transform in place of the SOM, and a multilayer perceptron (MLP) in place of the convolutional network for comparison. We use a database of 400 images of 40 individuals which contains quite a high degree of variability in expression, pose, and facial details. We analyze the computational complexity and discuss how new classes could be added to the trained recognizer.

Computationally efficient model predictive control algorithms a neural network approach

CERN Document Server

Ławryńczuk, Maciej

2014-01-01

This book thoroughly discusses computationally efficient (suboptimal) Model Predictive Control (MPC) techniques based on neural models. The subjects treated include: ·         A few types of suboptimal MPC algorithms in which a linear approximation of the model or of the predicted trajectory is successively calculated on-line and used for prediction. ·         Implementation details of the MPC algorithms for feedforward perceptron neural models, neural Hammerstein models, neural Wiener models and state-space neural models. ·         The MPC algorithms based on neural multi-models (inspired by the idea of predictive control). ·         The MPC algorithms with neural approximation with no on-line linearization. ·         The MPC algorithms with guaranteed stability and robustness. ·         Cooperation between the MPC algorithms and set-point optimization. Thanks to linearization (or neural approximation), the presented suboptimal algorithms do not require d...

Optimal multiple-information integration inherent in a ring neural network

International Nuclear Information System (INIS)

Takiyama, Ken

2017-01-01

Although several behavioral experiments have suggested that our neural system integrates multiple sources of information based on the certainty of each type of information in the manner of maximum-likelihood estimation, it is unclear how the maximum-likelihood estimation is implemented in our neural system. Here, I investigate the relationship between maximum-likelihood estimation and a widely used ring-type neural network model that is used as a model of visual, motor, or prefrontal cortices. Without any approximation or ansatz, I analytically demonstrate that the equilibrium of an order parameter in the neural network model exactly corresponds to the maximum-likelihood estimation when the strength of the symmetrical recurrent synaptic connectivity within a neural population is appropriately stronger than that of asymmetrical connectivity, that of local and external inputs, and that of symmetrical or asymmetrical connectivity between different neural populations. In this case, strengths of local and external inputs or those of symmetrical connectivity between different neural populations exactly correspond to the input certainty in maximum-likelihood estimation. Thus, my analysis suggests appropriately strong symmetrical recurrent connectivity as a possible candidate for implementing the maximum-likelihood estimation within our neural system. (paper)

Identifying Emotions on the Basis of Neural Activation.

Directory of Open Access Journals (Sweden)

Karim S Kassam

Full Text Available We attempt to determine the discriminability and organization of neural activation corresponding to the experience of specific emotions. Method actors were asked to self-induce nine emotional states (anger, disgust, envy, fear, happiness, lust, pride, sadness, and shame while in an fMRI scanner. Using a Gaussian Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1 neural activation of the same individual in other trials, 2 neural activation of other individuals who experienced similar trials, and 3 neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing.

Chaotic diagonal recurrent neural network

International Nuclear Information System (INIS)

Wang Xing-Yuan; Zhang Yi

2012-01-01

We propose a novel neural network based on a diagonal recurrent neural network and chaos, and its structure and learning algorithm are designed. The multilayer feedforward neural network, diagonal recurrent neural network, and chaotic diagonal recurrent neural network are used to approach the cubic symmetry map. The simulation results show that the approximation capability of the chaotic diagonal recurrent neural network is better than the other two neural networks. (interdisciplinary physics and related areas of science and technology)

Research on 3D power distribution of PWR reactor core based on RBF neural network

International Nuclear Information System (INIS)

Xia Hong; Li Bin; Liu Jianxin

2014-01-01

Real-time monitor for 3D power distribution is critical to nuclear safety and high efficiency of NPP's operation as well as the control system optimization. A method was proposed to set up a real-time monitor system for 3D power distribution by using of ex-core neutron detecting system and RBF neural network for improving the instantaneity of the monitoring results and reducing the fitting error of the 3D power distribution. A series of experiments were operated on a 300 MW PWR simulation system. The results demonstrate that the new monitor system works very well under condition of certain burnup range during the fuel cycle and reconstructs the real-time 3D distribution of reactor core power. The accuracy of the model is improved effectively with the help of several methods. (authors)

Toward a distributed free-floating wireless implantable neural recording system.

Science.gov (United States)

Pyungwoo Yeon; Xingyuan Tong; Byunghun Lee; Mirbozorgi, Abdollah; Ash, Bruce; Eckhardt, Helmut; Ghovanloo, Maysam

2016-08-01

To understand the complex correlations between neural networks across different regions in the brain and their functions at high spatiotemporal resolution, a tool is needed for obtaining long-term single unit activity (SUA) across the entire brain area. The concept and preliminary design of a distributed free-floating wireless implantable neural recording (FF-WINeR) system are presented, which can enabling SUA acquisition by dispersedly implanting tens to hundreds of untethered 1 mm3 neural recording probes, floating with the brain and operating wirelessly across the cortical surface. For powering FF-WINeR probes, a 3-coil link with an intermediate high-Q resonator provides a minimum S21 of -22.22 dB (in the body medium) and -21.23 dB (in air) at 2.8 cm coil separation, which translates to 0.76%/759 μW and 0.6%/604 μW of power transfer efficiency (PTE) / power delivered to a 9 kΩ load (PDL), in body and air, respectively. A mock-up FF-WINeR is implemented to explore microassembly method of the 1×1 mm2 micromachined silicon die with a bonding wire-wound coil and a tungsten micro-wire electrode. Circuit design methods to fit the active circuitry in only 0.96 mm2 of die area in a 130 nm standard CMOS process, and satisfy the strict power and performance requirements (in simulations) are discussed.

Neural Underpinnings of Decision Strategy Selection: A Review and a Theoretical Model.

Science.gov (United States)

Wichary, Szymon; Smolen, Tomasz

2016-01-01

In multi-attribute choice, decision makers use decision strategies to arrive at the final choice. What are the neural mechanisms underlying decision strategy selection? The first goal of this paper is to provide a literature review on the neural underpinnings and cognitive models of decision strategy selection and thus set the stage for a neurocognitive model of this process. The second goal is to outline such a unifying, mechanistic model that can explain the impact of noncognitive factors (e.g., affect, stress) on strategy selection. To this end, we review the evidence for the factors influencing strategy selection, the neural basis of strategy use and the cognitive models of this process. We also present the Bottom-Up Model of Strategy Selection (BUMSS). The model assumes that the use of the rational Weighted Additive strategy and the boundedly rational heuristic Take The Best can be explained by one unifying, neurophysiologically plausible mechanism, based on the interaction of the frontoparietal network, orbitofrontal cortex, anterior cingulate cortex and the brainstem nucleus locus coeruleus. According to BUMSS, there are three processes that form the bottom-up mechanism of decision strategy selection and lead to the final choice: (1) cue weight computation, (2) gain modulation, and (3) weighted additive evaluation of alternatives. We discuss how these processes might be implemented in the brain, and how this knowledge allows us to formulate novel predictions linking strategy use and neural signals.

Neural Underpinnings of Decision Strategy Selection: A Review and a Theoretical Model

Science.gov (United States)

Wichary, Szymon; Smolen, Tomasz

2016-01-01

In multi-attribute choice, decision makers use decision strategies to arrive at the final choice. What are the neural mechanisms underlying decision strategy selection? The first goal of this paper is to provide a literature review on the neural underpinnings and cognitive models of decision strategy selection and thus set the stage for a neurocognitive model of this process. The second goal is to outline such a unifying, mechanistic model that can explain the impact of noncognitive factors (e.g., affect, stress) on strategy selection. To this end, we review the evidence for the factors influencing strategy selection, the neural basis of strategy use and the cognitive models of this process. We also present the Bottom-Up Model of Strategy Selection (BUMSS). The model assumes that the use of the rational Weighted Additive strategy and the boundedly rational heuristic Take The Best can be explained by one unifying, neurophysiologically plausible mechanism, based on the interaction of the frontoparietal network, orbitofrontal cortex, anterior cingulate cortex and the brainstem nucleus locus coeruleus. According to BUMSS, there are three processes that form the bottom-up mechanism of decision strategy selection and lead to the final choice: (1) cue weight computation, (2) gain modulation, and (3) weighted additive evaluation of alternatives. We discuss how these processes might be implemented in the brain, and how this knowledge allows us to formulate novel predictions linking strategy use and neural signals. PMID:27877103

Real-time camera-based face detection using a modified LAMSTAR neural network system

Science.gov (United States)

Girado, Javier I.; Sandin, Daniel J.; DeFanti, Thomas A.; Wolf, Laura K.

2003-03-01

This paper describes a cost-effective, real-time (640x480 at 30Hz) upright frontal face detector as part of an ongoing project to develop a video-based, tetherless 3D head position and orientation tracking system. The work is specifically targeted for auto-stereoscopic displays and projection-based virtual reality systems. The proposed face detector is based on a modified LAMSTAR neural network system. At the input stage, after achieving image normalization and equalization, a sub-window analyzes facial features using a neural network. The sub-window is segmented, and each part is fed to a neural network layer consisting of a Kohonen Self-Organizing Map (SOM). The output of the SOM neural networks are interconnected and related by correlation-links, and can hence determine the presence of a face with enough redundancy to provide a high detection rate. To avoid tracking multiple faces simultaneously, the system is initially trained to track only the face centered in a box superimposed on the display. The system is also rotationally and size invariant to a certain degree.

Neural networks for sensor validation and plant-wide monitoring

International Nuclear Information System (INIS)

Eryurek, E.

1991-08-01

The feasibility of using neural networks to characterize one or more variables as a function of other than related variables has been studied. Neural network or parallel distributed processing is found to be highly suitable for the development of relationships among various parameters. A sensor failure detection is studied, and it is shown that neural network models can be used to estimate the sensor readings during the absence of a sensor. (author). 4 refs.; 3 figs

An on-line non-leptonic neural trigger applied to an experiment looking for beauty

CERN Document Server

Baldanza, C; Cotta-Ramusino, A; D'Antone, I; Malferrari, L; Mazzanti, P; Odorici, F; Odorico, R; Zuffa, M; Bruschini, C; Musico, P; Novelli, P; Passaseo, M

1994-01-01

Results from a non-leptonic neural-network trigger hosted by experiment WA92, looking for beauty particle production from 350 GeV 1t- on a Cu target, are presented. The neural trigger has been used to send on a special data stream (the Fast Stream) events to be analyzed with high priority. The non-leptonic signature uses microvertex detector data and was devised so as to enrich the fraction of events containing C3 secondary vertices (i.e, vertices having three tracks whith sum of electric charges equal to +1 or -1). The neural trigger module consists of a VME crate hosting two ET ANN analog neural chips from Intel. The neural trigger operated for two continuous weeks during the WA92 1 993 run. For an acceptance of 15% for C3 events, the neural trigger yields a C3 enrichment factor of 6.6-7.l (depending on the event sample considered), which multiplied by that already provided by the standard non-leptonic trigger leads to a global C3 enrichment factor of -1 50. In the event sample selected by the neural trigge...

Knowledge Based 3d Building Model Recognition Using Convolutional Neural Networks from LIDAR and Aerial Imageries

Science.gov (United States)

Alidoost, F.; Arefi, H.

2016-06-01

In recent years, with the development of the high resolution data acquisition technologies, many different approaches and algorithms have been presented to extract the accurate and timely updated 3D models of buildings as a key element of city structures for numerous applications in urban mapping. In this paper, a novel and model-based approach is proposed for automatic recognition of buildings' roof models such as flat, gable, hip, and pyramid hip roof models based on deep structures for hierarchical learning of features that are extracted from both LiDAR and aerial ortho-photos. The main steps of this approach include building segmentation, feature extraction and learning, and finally building roof labeling in a supervised pre-trained Convolutional Neural Network (CNN) framework to have an automatic recognition system for various types of buildings over an urban area. In this framework, the height information provides invariant geometric features for convolutional neural network to localize the boundary of each individual roofs. CNN is a kind of feed-forward neural network with the multilayer perceptron concept which consists of a number of convolutional and subsampling layers in an adaptable structure and it is widely used in pattern recognition and object detection application. Since the training dataset is a small library of labeled models for different shapes of roofs, the computation time of learning can be decreased significantly using the pre-trained models. The experimental results highlight the effectiveness of the deep learning approach to detect and extract the pattern of buildings' roofs automatically considering the complementary nature of height and RGB information.

Computational modeling of neural plasticity for self-organization of neural networks.

Science.gov (United States)

Chrol-Cannon, Joseph; Jin, Yaochu

2014-11-01

Self-organization in biological nervous systems during the lifetime is known to largely occur through a process of plasticity that is dependent upon the spike-timing activity in connected neurons. In the field of computational neuroscience, much effort has been dedicated to building up computational models of neural plasticity to replicate experimental data. Most recently, increasing attention has been paid to understanding the role of neural plasticity in functional and structural neural self-organization, as well as its influence on the learning performance of neural networks for accomplishing machine learning tasks such as classification and regression. Although many ideas and hypothesis have been suggested, the relationship between the structure, dynamics and learning performance of neural networks remains elusive. The purpose of this article is to review the most important computational models for neural plasticity and discuss various ideas about neural plasticity's role. Finally, we suggest a few promising research directions, in particular those along the line that combines findings in computational neuroscience and systems biology, and their synergetic roles in understanding learning, memory and cognition, thereby bridging the gap between computational neuroscience, systems biology and computational intelligence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Deep 3D convolution neural network for CT brain hemorrhage classification

Science.gov (United States)

Jnawali, Kamal; Arbabshirani, Mohammad R.; Rao, Navalgund; Patel, Alpen A.

2018-02-01

Intracranial hemorrhage is a critical conditional with the high mortality rate that is typically diagnosed based on head computer tomography (CT) images. Deep learning algorithms, in particular, convolution neural networks (CNN), are becoming the methodology of choice in medical image analysis for a variety of applications such as computer-aided diagnosis, and segmentation. In this study, we propose a fully automated deep learning framework which learns to detect brain hemorrhage based on cross sectional CT images. The dataset for this work consists of 40,367 3D head CT studies (over 1.5 million 2D images) acquired retrospectively over a decade from multiple radiology facilities at Geisinger Health System. The proposed algorithm first extracts features using 3D CNN and then detects brain hemorrhage using the logistic function as the last layer of the network. Finally, we created an ensemble of three different 3D CNN architectures to improve the classification accuracy. The area under the curve (AUC) of the receiver operator characteristic (ROC) curve of the ensemble of three architectures was 0.87. Their results are very promising considering the fact that the head CT studies were not controlled for slice thickness, scanner type, study protocol or any other settings. Moreover, the proposed algorithm reliably detected various types of hemorrhage within the skull. This work is one of the first applications of 3D CNN trained on a large dataset of cross sectional medical images for detection of a critical radiological condition

Advanced Applications of Neural Networks and Artificial Intelligence: A Review

OpenAIRE

Koushal Kumar; Gour Sundar Mitra Thakur

2012-01-01

Artificial Neural Network is a branch of Artificial intelligence and has been accepted as a new computing technology in computer science fields. This paper reviews the field of Artificial intelligence and focusing on recent applications which uses Artificial Neural Networks (ANN’s) and Artificial Intelligence (AI). It also considers the integration of neural networks with other computing methods Such as fuzzy logic to enhance the interpretation ability of data. Artificial Neural Networks is c...

Design of efficient and safe neural stimulators a multidisciplinary approach

CERN Document Server

van Dongen, Marijn

2016-01-01

This book discusses the design of neural stimulator systems which are used for the treatment of a wide variety of brain disorders such as Parkinson’s, depression and tinnitus. Whereas many existing books treating neural stimulation focus on one particular design aspect, such as the electrical design of the stimulator, this book uses a multidisciplinary approach: by combining the fields of neuroscience, electrophysiology and electrical engineering a thorough understanding of the complete neural stimulation chain is created (from the stimulation IC down to the neural cell). This multidisciplinary approach enables readers to gain new insights into stimulator design, while context is provided by presenting innovative design examples. Provides a single-source, multidisciplinary reference to the field of neural stimulation, bridging an important knowledge gap among the fields of bioelectricity, neuroscience, neuroengineering and microelectronics;Uses a top-down approach to understanding the neural activation proc...

A Simple Quantum Neural Net with a Periodic Activation Function

OpenAIRE

Daskin, Ammar

2018-01-01

In this paper, we propose a simple neural net that requires only $O(nlog_2k)$ number of qubits and $O(nk)$ quantum gates: Here, $n$ is the number of input parameters, and $k$ is the number of weights applied to these parameters in the proposed neural net. We describe the network in terms of a quantum circuit, and then draw its equivalent classical neural net which involves $O(k^n)$ nodes in the hidden layer. Then, we show that the network uses a periodic activation function of cosine values o...

Generation and properties of a new human ventral mesencephalic neural stem cell line

DEFF Research Database (Denmark)

Villa, Ana; Liste, Isabel; Courtois, Elise T

2009-01-01

. Here we report the generation of a new stable cell line of human neural stem cells derived from ventral mesencephalon (hVM1) based on v-myc immortalization. The cells expressed neural stem cell and radial glia markers like nestin, vimentin and 3CB2 under proliferation conditions. After withdrawal......Neural stem cells (NSCs) are powerful research tools for the design and discovery of new approaches to cell therapy in neurodegenerative diseases like Parkinson's disease. Several epigenetic and genetic strategies have been tested for long-term maintenance and expansion of these cells in vitro...... derivatives may constitute good candidates for the study of development and physiology of human dopaminergic neurons in vitro, and to develop tools for Parkinson's disease cell replacement preclinical research and drug testing....

Social priming modulates the neural response to ostracism: a new exploratory approach.

Science.gov (United States)

Hudac, Caitlin M

2018-04-16

The present study sought to evaluate whether social priming modulates neural responses to ostracism, such that making arbitrary interpersonal decisions increases the experience of social exclusion more than making arbitrary physical decisions. This exploratory event-related potential (ERP) study utilized the Lunchroom task, in which adults (N = 28) first selected one of two options that included either interpersonal or physical descriptors. Participants then received ostracism outcome feedback within a lunchroom scenario in which they were either excluded (e.g. sitting alone) or included (e.g. surrounded by others). While the N2 component was sensitive to priming decision condition, only the P3 component discriminated between ostracism decisions. Further inspection of the neural sources indicated that the amygdala, anterior cingulate cortex, and superior temporal gyrus were more engaged for exclusion than inclusion conditions during both N2 and P3 temporal windows. Evaluation of temporal source dynamics suggest that the effects of ostracism are predominant between 250-500 ms and were larger following interpersonal than physical decisions. These results suggest that being ostracized evokes a larger neural response that is modulated following priming of the social brain.

Neural Generalized Predictive Control of a non-linear Process

DEFF Research Database (Denmark)

Sørensen, Paul Haase; Nørgård, Peter Magnus; Ravn, Ole

1998-01-01

The use of neural network in non-linear control is made difficult by the fact the stability and robustness is not guaranteed and that the implementation in real time is non-trivial. In this paper we introduce a predictive controller based on a neural network model which has promising stability qu...... detail and discuss the implementation difficulties. The neural generalized predictive controller is tested on a pneumatic servo sys-tem.......The use of neural network in non-linear control is made difficult by the fact the stability and robustness is not guaranteed and that the implementation in real time is non-trivial. In this paper we introduce a predictive controller based on a neural network model which has promising stability...... qualities. The controller is a non-linear version of the well-known generalized predictive controller developed in linear control theory. It involves minimization of a cost function which in the present case has to be done numerically. Therefore, we develop the numerical algorithms necessary in substantial...

Visual guidance of a pig evisceration robot using neural networks

DEFF Research Database (Denmark)

Christensen, S.S.; Andersen, A.W.; Jørgensen, T.M.

1996-01-01

The application of a RAM-based neural network to robot vision is demonstrated for the guidance of a pig evisceration robot. Tests of the combined robot-vision system have been performed at an abattoir. The vision system locates a set of feature points on a pig carcass and transmits the 3D coordin...

Neural differentiation of mouse embryonic stem cells as a tool to assess developmental neurotoxicity in vitro.

Science.gov (United States)

Visan, Anke; Hayess, Katrin; Sittner, Dana; Pohl, Elena E; Riebeling, Christian; Slawik, Birgitta; Gulich, Konrad; Oelgeschläger, Michael; Luch, Andreas; Seiler, Andrea E M

2012-10-01

Mouse embryonic stem cells (mESCs) represent an attractive cellular system for in vitro studies in developmental biology as well as toxicology because of their potential to differentiate into all fetal cell lineages. The present study aims to establish an in vitro system for developmental neurotoxicity testing employing mESCs. We developed a robust and reproducible protocol for fast and efficient differentiation of the mESC line D3 into neural cells, optimized with regard to chemical testing. Morphological examination and immunocytochemical staining confirmed the presence of different neural cell types, including neural progenitors, neurons, astrocytes, oligodendrocytes, and radial glial cells. Neurons derived from D3 cells expressed the synaptic proteins PSD95 and synaptophysin, and the neurotransmitters serotonin and γ-aminobutyric acid. Calcium ion imaging revealed the presence of functionally active glutamate and dopamine receptors. In addition, flow cytometry analysis of the neuron-specific marker protein MAP2 on day 12 after induction of differentiation demonstrated a concentration dependent effect of the neurodevelopmental toxicants methylmercury chloride, chlorpyrifos, and lead acetate on neuronal differentiation. The current study shows that D3 mESCs differentiate efficiently into neural cells involving a neurosphere-like state and that this system is suitable to detect adverse effects of neurodevelopmental toxicants. Therefore, we propose that the protocol for differentiation of mESCs into neural cells described here could constitute one component of an in vitro testing strategy for developmental neurotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

The Neural Basis of and a Common Neural Circuitry in Different Types of Pro-social Behavior

Directory of Open Access Journals (Sweden)

Jun Luo

2018-06-01

Full Text Available Pro-social behaviors are voluntary behaviors that benefit other people or society as a whole, such as charitable donations, cooperation, trust, altruistic punishment, and fairness. These behaviors have been widely described through non self-interest decision-making in behavioral experimental studies and are thought to be increased by social preference motives. Importantly, recent studies using a combination of neuroimaging and brain stimulation, designed to reveal the neural mechanisms of pro-social behaviors, have found that a wide range of brain areas, specifically the prefrontal cortex, anterior insula, anterior cingulate cortex, and amygdala, are correlated or causally related with pro-social behaviors. In this review, we summarize the research on the neural basis of various kinds of pro-social behaviors and describe a common shared neural circuitry of these pro-social behaviors. We introduce several general ways in which experimental economics and neuroscience can be combined to develop important contributions to understanding social decision-making and pro-social behaviors. Future research should attempt to explore the neural circuitry between the frontal lobes and deeper brain areas.

Evolution of neural crest and placodes: amphioxus as a model for the ancestral vertebrate?

Science.gov (United States)

Holland, L. Z.; Holland, N. D.

2001-01-01

Recent studies of protochordates (ascidian tunicates and amphioxus) have given insights into possible ancestors of 2 of the characteristic features of the vertebrate head: neural crest and placodes. The neural crest probably evolved from cells on either side of the neural plate-epidermis boundary in a protochordate ancestral to the vertebrates. In amphioxus, homologues of several vertebrate neural crest marker genes (BMP2/4, Pax3/7, Msx, Dll and Snail) are expressed at the edges of the neural plate and/or adjacent nonneural ectoderm. Some of these markers are also similarly expressed in tunicates. In protochordates, however, these cells, unlike vertebrate neural crest, neither migrate as individuals through embryonic tissues nor differentiate into a wide spectrum of cell types. Therefore, while the protochordate ancestor of the vertebrates probably had the beginnings of a genetic programme for neural crest formation, this programme was augmented in the earliest vertebrates to attain definitive neural crest. Clear homologues of vertebrate placodes are lacking in protochordates. However, both amphioxus and tunicates have ectodermal sensory cells. In tunicates these are all primary neurons, sending axons to the central nervous system, while in amphioxus, the ectodermal sensory cells include both primary neurons and secondary neurons lacking axons. Comparisons of developmental gene expression suggest that the anterior ectoderm in amphioxus may be homologous to the vertebrate olfactory placode, the only vertebrate placode with primary, not secondary, neurons. Similarly, biochemical, morphological and gene expression data suggest that amphioxus and tunicates also have homologues of the adenohypophysis, one of the few vertebrate structures derived from nonneurogenic placodes. In contrast, the origin of the other vertebrate placodes is very uncertain.

Regeneración axonal posterior a lesiones traumáticas de médula espinal: Papel crítico de galectina-1

Directory of Open Access Journals (Sweden)

Héctor R Quintá

2014-08-01

Full Text Available Al producirse una lesión de médula espinal (LME, un sinnúmero de proteínas inhibidoras de la regeneración axonal ocupan el sitio de lesión en forma secuencial. La primer proteína en llegar al mismo se conoce como semaforina 3A (Sema3A, siendo además una de las más potentes por su acción de inhibir la regeneración axonal. A nivel mecanístico la unión de esta proteína al complejo-receptor neuronal neuropilin-1 (NRP-1/PlexinA4 evita que se produzca regeneración axonal. En este trabajo de revisión se discutirá la acción de galectin-1 (Gal-1, una proteína endógena de unión a glicanos, que selectivamente se une al complejo-receptor NRP-1/PlexinA4 de las neuronas lesionadas a través de un mecanismo dependiente de interacciones lectina-glicano, interrumpiendo la señalización generada por Sema3A y permitiendo de esta manera la regeneración axonal y recuperación locomotora luego de producirse la LME. Mientras ambas formas de Gal-1 (monomérica y dimérica contribuyen a la inactivación de la microglia, solo la forma dimérica de Gal-1 es capaz de unirse al complejo-receptor NRP-1/PlexinA4 y promover regeneración axonal. Por lo tanto, Gal-1 dimérica produce recuperación de las lesiones espinales interfiriendo en la señalización de Sema3A a través de la unión al complejo-receptor NRP-1/PlexinA4, sugiriendo el uso de esta lectina en su forma dimérica para el tratamiento de pacientes con LME.

Prediction based chaos control via a new neural network

International Nuclear Information System (INIS)

Shen Liqun; Wang Mao; Liu Wanyu; Sun Guanghui

2008-01-01

In this Letter, a new chaos control scheme based on chaos prediction is proposed. To perform chaos prediction, a new neural network architecture for complex nonlinear approximation is proposed. And the difficulty in building and training the neural network is also reduced. Simulation results of Logistic map and Lorenz system show the effectiveness of the proposed chaos control scheme and the proposed neural network

Representation of neutron noise data using neural networks

International Nuclear Information System (INIS)

Korsah, K.; Damiano, B.; Wood, R.T.

1992-01-01

This paper describes a neural network-based method of representing neutron noise spectra using a model developed at the Oak Ridge National Laboratory (ORNL). The backpropagation neural network learned to represent neutron noise data in terms of four descriptors, and the network response matched calculated values to within 3.5 percent. These preliminary results are encouraging, and further research is directed towards the application of neural networks in a diagnostics system for the identification of the causes of changes in structural spectral resonances. This work is part of our current investigation of advanced technologies such as expert systems and neural networks for neutron noise data reduction, analysis, and interpretation. The objective is to improve the state-of-the-art of noise analysis as a diagnostic tool for nuclear power plants and other mechanical systems