Online neural trigger for optimizing data acquisition during particle beam calibration tests with calorimeters

CERN Document Server

Da Silva, P V M; De Seixas, J M; Ferreira, B C

2004-01-01

For LHC, the hadronic calorimetry of the ATLAS detector is performed by Tilecal, a scintillating tile calorimeter. For calibration purposes, a fraction of the Tilecal modules is placed in particle beam lines. Despite beam high quality, experimental beam contamination is observed and this masks the actual performance of the calorimeter. For optimizing the calibration task, an online neural particle classifier was developed for Tilecal. Envisaging a neural trigger for incoming particles, a neural process runs integrated to the data acquisition task and performs online training for particle identification. The neural classification performance is evaluated by correlating the neural response to classical methodology, confirming an ability for outsider identification at levels as high as 99.3%.

Factors Released from Endothelial Cells Exposed to Flow Impact Adhesion, Proliferation, and Fate Choice in the Adult Neural Stem Cell Lineage.

Science.gov (United States)

Dumont, Courtney M; Piselli, Jennifer M; Kazi, Nadeem; Bowman, Evan; Li, Guoyun; Linhardt, Robert J; Temple, Sally; Dai, Guohao; Thompson, Deanna M

2017-08-15

The microvasculature within the neural stem cell (NSC) niche promotes self-renewal and regulates lineage progression. Previous work identified endothelial-produced soluble factors as key regulators of neural progenitor cell (NPC) fate and proliferation; however, endothelial cells (ECs) are sensitive to local hemodynamics, and the effect of this key physiological process has not been defined. In this study, we evaluated adult mouse NPC response to soluble factors isolated from static or dynamic (flow) EC cultures. Endothelial factors generated under dynamic conditions significantly increased neuronal differentiation, while those released under static conditions stimulated oligodendrocyte differentiation. Flow increases EC release of neurogenic factors and of heparin sulfate glycosaminoglycans that increase their bioactivity, likely underlying the enhanced neuronal differentiation. Additionally, endothelial factors, especially from static conditions, promoted adherent growth. Together, our data suggest that blood flow may impact proliferation, adhesion, and the neuron-glial fate choice of adult NPCs, with implications for diseases and aging that reduce flow.

Neural Stimulation Has a Long-Term Effect on Foreign Vocabulary Acquisition.

Science.gov (United States)

Pasqualotto, Achille; Kobanbay, Begüm; Proulx, Michael J

2015-01-01

Acquisition of a foreign language is a challenging task that is becoming increasingly more important in the world nowadays. There is evidence suggesting that the frontal and temporal cortices are involved in language processing and comprehension, but it is still unknown whether foreign language acquisition recruits additional cortical areas in a causal manner. For the first time, we used transcranial random noise stimulation on the frontal and parietal brain areas, in order to compare its effect on the acquisition of unknown foreign words and a sham, or placebo, condition was also included. This type of noninvasive neural stimulation enhances cortical activity by boosting the spontaneous activity of neurons. Foreign vocabulary acquisition was tested both immediately and seven days after the stimulation. We found that stimulation on the posterior parietal, but not the dorsolateral prefrontal cortex or sham stimulation, significantly improved the memory performance in the long term. These results suggest that the posterior parietal cortex is directly involved in acquisition of foreign vocabulary, thus extending the "linguistic network" to this area.

The influence of immunosuppressive drugs on neural stem/progenitor cell fate in vitro

Energy Technology Data Exchange (ETDEWEB)

Skardelly, Marco, E-mail: Marco.Skardelly@med.uni-tuebingen.de [Department of Neurosurgery, University Hospital, Leipzig (Germany); Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig (Germany); Glien, Anja; Groba, Claudia; Schlichting, Nadine [Department of Neurosurgery, University Hospital, Leipzig (Germany); Kamprad, Manja [Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Leipzig (Germany); Meixensberger, Juergen [Department of Neurosurgery, University Hospital, Leipzig (Germany); Milosevic, Javorina [Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig (Germany)

2013-12-10

In allogenic and xenogenic transplantation, adequate immunosuppression plays a major role in graft survival, especially over the long term. The effect of immunosuppressive drugs on neural stem/progenitor cell fate has not been sufficiently explored. The focus of this study is to systematically investigate the effects of the following four different immunotherapeutic strategies on human neural progenitor cell survival/death, proliferation, metabolic activity, differentiation and migration in vitro: (1) cyclosporine A (CsA), a calcineurin inhibitor; (2) everolimus (RAD001), an mTOR-inhibitor; (3) mycophenolic acid (MPA, mycophenolate), an inhibitor of inosine monophosphate dehydrogenase and (4) prednisolone, a steroid. At the minimum effective concentration (MEC), we found a prominent decrease in hNPCs' proliferative capacity (BrdU incorporation), especially for CsA and MPA, and an alteration of the NAD(P)H-dependent metabolic activity. Cell death rate, neurogenesis, gliogenesis and cell migration remained mostly unaffected under these conditions for all four immunosuppressants, except for apoptotic cell death, which was significantly increased by MPA treatment. - Highlights: • Four immunosuppresants (ISs) were tested in human neural progenitor cells in vitro. • Cyclosporine A and mycophenolic acid showed a prominent anti-proliferative activity • Mycophenolic acid exhibited a significant pro-apoptotic effect. • NAD(P)H-dependent metabolic activity was occasionally induced by ISs. • Neuronal differentiation and migration potential remained unaffected by ISs treatment.

The use of neural networks in the D0 data acquisition system

International Nuclear Information System (INIS)

Cutts, D.; Hoftun, J.S.; Sornborger, A.; Astur, R.V.; Johnson, C.R.; Zeller, R.T.

1989-01-01

We discuss the possible application of algorithms derived from neural networks to the D0 experiment. The D0 data acquisition system is based on a large farm of MicroVAXes, each independently performing real-time event filtering. A new generation of multiport memories in each MicroVAX node will enable special function processors to have direct access to event data. We describe an exploratory study of back propagation neural networks, such as might be configured in the nodes, for more efficient event filtering. 9 refs., 3 figs., 1 tab

New roles for Nanos in neural cell fate determination revealed by studies in a cnidarian.

Science.gov (United States)

Kanska, Justyna; Frank, Uri

2013-07-15

Nanos is a pan-metazoan germline marker, important for germ cell development and maintenance. In flies, Nanos also acts in posterior and neural development, but these functions have not been demonstrated experimentally in other animals. Using the cnidarian Hydractinia we have uncovered novel roles for Nanos in neural cell fate determination. Ectopic expression of Nanos2 increased the numbers of embryonic stinging cell progenitors, but decreased the numbers of neurons. Downregulation of Nanos2 had the opposite effect. Furthermore, Nanos2 blocked maturation of committed, post-mitotic nematoblasts. Hence, Nanos2 acts as a switch between two differentiation pathways, increasing the numbers of nematoblasts at the expense of neuroblasts, but preventing nematocyte maturation. Nanos2 ectopic expression also caused patterning defects, but these were not associated with deregulation of Wnt signaling, showing that the basic anterior-posterior polarity remained intact, and suggesting that numerical imbalance between nematocytes and neurons might have caused these defects, affecting axial patterning only indirectly. We propose that the functions of Nanos in germ cells and in neural development are evolutionarily conserved, but its role in posterior patterning is an insect or arthropod innovation.

Cell fate control in the developing central nervous system

Energy Technology Data Exchange (ETDEWEB)

Guérout, Nicolas; Li, Xiaofei; Barnabé-Heider, Fanie, E-mail: Fanie.Barnabe-Heider@ki.se

2014-02-01

The principal neural cell types forming the mature central nervous system (CNS) are now understood to be diverse. This cellular subtype diversity originates to a large extent from the specification of the earlier proliferating progenitor populations during development. Here, we review the processes governing the differentiation of a common neuroepithelial cell progenitor pool into mature neurons, astrocytes, oligodendrocytes, ependymal cells and adult stem cells. We focus on studies performed in mice and involving two distinct CNS structures: the spinal cord and the cerebral cortex. Understanding the origin, specification and developmental regulators of neural cells will ultimately impact comprehension and treatments of neurological disorders and diseases. - Highlights: • Similar mechanisms regulate cell fate in different CNS cell types and structures. • Cell fate regulators operate in a spatial–temporal manner. • Different neural cell types rely on the generation of a diversity of progenitor cells. • Cell fate decision is dictated by the integration of intrinsic and extrinsic signals.

Cell fate control in the developing central nervous system

International Nuclear Information System (INIS)

Guérout, Nicolas; Li, Xiaofei; Barnabé-Heider, Fanie

2014-01-01

The principal neural cell types forming the mature central nervous system (CNS) are now understood to be diverse. This cellular subtype diversity originates to a large extent from the specification of the earlier proliferating progenitor populations during development. Here, we review the processes governing the differentiation of a common neuroepithelial cell progenitor pool into mature neurons, astrocytes, oligodendrocytes, ependymal cells and adult stem cells. We focus on studies performed in mice and involving two distinct CNS structures: the spinal cord and the cerebral cortex. Understanding the origin, specification and developmental regulators of neural cells will ultimately impact comprehension and treatments of neurological disorders and diseases. - Highlights: • Similar mechanisms regulate cell fate in different CNS cell types and structures. • Cell fate regulators operate in a spatial–temporal manner. • Different neural cell types rely on the generation of a diversity of progenitor cells. • Cell fate decision is dictated by the integration of intrinsic and extrinsic signals

High glucose alters the expression of genes involved in proliferation and cell-fate specification of embryonic neural stem cells.

Science.gov (United States)

Fu, J; Tay, S S W; Ling, E A; Dheen, S T

2006-05-01

Maternal diabetes induces neural tube defects during embryogenesis. Since the neural tube is derived from neural stem cells (NSCs), it is hypothesised that in diabetic pregnancy neural tube defects result from altered expression of developmental control genes, leading to abnormal proliferation and cell-fate choice of NSCs. Cell viability, proliferation index and apoptosis of NSCs and differentiated cells from mice exposed to physiological or high glucose concentration medium were examined by a tetrazolium salt assay, 5-bromo-2'-deoxyuridine incorporation, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling and immunocytochemistry. Expression of developmental genes, including sonic hedgehog (Shh), bone morphogenetic protein 4 (Bmp4), neurogenin 1/2 (Neurog1/2), achaete-scute complex-like 1 (Ascl1), oligodendrocyte transcription factor 1 (Olig1), oligodendrocyte lineage transcription factor 2 (Olig2), hairy and enhancer of split 1/5 (Hes1/5) and delta-like 1 (Dll1), was analysed by real-time RT-PCR. Proliferation index and neuronal specification in the forebrain of embryos at embryonic day 11.5 were examined histologically. High glucose decreased the proliferation of NSCs and differentiated cells. The incidence of apoptosis was increased in NSCs treated with high glucose, but not in the differentiated cells. High glucose also accelerated neuronal and glial differentiation from NSCs. The decreased proliferation index and early differentiation of neurons were evident in the telencephalon of embryos derived from diabetic mice. Exposure to high glucose altered the mRNA expression levels of Shh, Bmp4, Neurog1/2, Ascl1, Hes1, Dll1 and Olig1 in NSCs and Shh, Dll1, Neurog1/2 and Hes5 in differentiated cells. The changes in proliferation and differentiation of NSCs exposed to high glucose are associated with altered expression of genes that are involved in cell-cycle progression and cell-fate specification during neurulation. These changes may form the

Regulation of spindle orientation and neural stem cell fate in the Drosophila optic lobe

Directory of Open Access Journals (Sweden)

Brand Andrea H

2007-01-01

Full Text Available Abstract Background The choice of a stem cell to divide symmetrically or asymmetrically has profound consequences for development and disease. Unregulated symmetric division promotes tumor formation, whereas inappropriate asymmetric division affects organ morphogenesis. Despite its importance, little is known about how spindle positioning is regulated. In some tissues cell fate appears to dictate the type of cell division, whereas in other tissues it is thought that stochastic variation in spindle position dictates subsequent sibling cell fate. Results Here we investigate the relationship between neural progenitor identity and spindle positioning in the Drosophila optic lobe. We use molecular markers and live imaging to show that there are two populations of progenitors in the optic lobe: symmetrically dividing neuroepithelial cells and asymmetrically dividing neuroblasts. We use genetically marked single cell clones to show that neuroepithelial cells give rise to neuroblasts. To determine if a change in spindle orientation can trigger a neuroepithelial to neuroblast transition, we force neuroepithelial cells to divide along their apical/basal axis by misexpressing Inscuteable. We find that this does not induce neuroblasts, nor does it promote premature neuronal differentiation. Conclusion We show that symmetrically dividing neuroepithelial cells give rise to asymmetrically dividing neuroblasts in the optic lobe, and that regulation of spindle orientation and division symmetry is a consequence of cell type specification, rather than a mechanism for generating cell type diversity.

Forecasting the Acquisition of University Spin-Outs: An RBF Neural Network Approach

Directory of Open Access Journals (Sweden)

Weiwei Liu

2017-01-01

Full Text Available University spin-outs (USOs, creating businesses from university intellectual property, are a relatively common phenomena. As a knowledge transfer channel, the spin-out business model is attracting extensive attention. In this paper, the impacts of six equities on the acquisition of USOs, including founders, university, banks, business angels, venture capitals, and other equity, are comprehensively analyzed based on theoretical and empirical studies. Firstly, the average distribution of spin-out equity at formation is calculated based on the sample data of 350 UK USOs. According to this distribution, a radial basis function (RBF neural network (NN model is employed to forecast the effects of each equity on the acquisition. To improve the classification accuracy, the novel set-membership method is adopted in the training process of the RBF NN. Furthermore, a simulation test is carried out to measure the effects of six equities on the acquisition of USOs. The simulation results show that the increase of university’s equity has a negative effect on the acquisition of USOs, whereas the increase of remaining five equities has positive effects. Finally, three suggestions are provided to promote the development and growth of USOs.

Apical versus Basal Neurogenesis Directs Cortical Interneuron Subclass Fate

Directory of Open Access Journals (Sweden)

Timothy J. Petros

2015-11-01

Full Text Available Fate determination in the mammalian telencephalon, with its diversity of neuronal subtypes and relevance to neuropsychiatric disease, remains a critical area of study in neuroscience. Most studies investigating this topic focus on the diversity of neural progenitors within spatial and temporal domains along the lateral ventricles. Often overlooked is whether the location of neurogenesis within a fate-restricted domain is associated with, or instructive for, distinct neuronal fates. Here, we use in vivo fate mapping and the manipulation of neurogenic location to demonstrate that apical versus basal neurogenesis influences the fate determination of major subgroups of cortical interneurons derived from the subcortical telencephalon. Somatostatin-expressing interneurons arise mainly from apical divisions along the ventricular surface, whereas parvalbumin-expressing interneurons originate predominantly from basal divisions in the subventricular zone. As manipulations that shift neurogenic location alter interneuron subclass fate, these results add an additional dimension to the spatial-temporal determinants of neuronal fate determination.

Interactive natural language acquisition in a multi-modal recurrent neural architecture

Science.gov (United States)

Heinrich, Stefan; Wermter, Stefan

2018-01-01

For the complex human brain that enables us to communicate in natural language, we gathered good understandings of principles underlying language acquisition and processing, knowledge about sociocultural conditions, and insights into activity patterns in the brain. However, we were not yet able to understand the behavioural and mechanistic characteristics for natural language and how mechanisms in the brain allow to acquire and process language. In bridging the insights from behavioural psychology and neuroscience, the goal of this paper is to contribute a computational understanding of appropriate characteristics that favour language acquisition. Accordingly, we provide concepts and refinements in cognitive modelling regarding principles and mechanisms in the brain and propose a neurocognitively plausible model for embodied language acquisition from real-world interaction of a humanoid robot with its environment. In particular, the architecture consists of a continuous time recurrent neural network, where parts have different leakage characteristics and thus operate on multiple timescales for every modality and the association of the higher level nodes of all modalities into cell assemblies. The model is capable of learning language production grounded in both, temporal dynamic somatosensation and vision, and features hierarchical concept abstraction, concept decomposition, multi-modal integration, and self-organisation of latent representations.

The neural basis of task switching changes with skill acquisition

Directory of Open Access Journals (Sweden)

Koji eJimura

2014-05-01

Full Text Available Learning novel skills involves reorganization and optimization of cognitive processing involving a broad network of brain regions. Previous work has shown asymmetric costs of switching to a well-trained task versus a poorly-trained task, but the neural basis of these differential switch costs is unclear. The current study examined the neural signature of task switching in the context of acquisition of new skill. Human participants alternated randomly between a novel visual task (mirror-reversed word reading and a highly practiced one (plain word reading, allowing the isolation of task switching and skill set maintenance. Two scan sessions were separated by two weeks, with behavioral training on the mirror reading task in between the two sessions. Broad cortical regions, including bilateral prefrontal, parietal, and extrastriate cortices, showed decreased activity associated with learning of the mirror reading skill. In contrast, learning to switch to the novel skill was associated with decreased activity in a focal subcortical region in the dorsal striatum. Switching to the highly practiced task was associated with a non-overlapping set of regions, suggesting substantial differences in the neural substrates of switching as a function of task skill. Searchlight multivariate pattern analysis also revealed that learning was associated with decreased pattern information for mirror versus plain reading tasks in fronto-parietal regions. Inferior frontal junction and posterior parietal cortex showed a joint effect of univariate activation and pattern information. These results suggest distinct learning mechanisms task performance and executive control as a function of learning.

Prolonged Mitosis of Neural Progenitors Alters Cell Fate in the Developing Brain.

Science.gov (United States)

Pilaz, Louis-Jan; McMahon, John J; Miller, Emily E; Lennox, Ashley L; Suzuki, Aussie; Salmon, Edward; Silver, Debra L

2016-01-06

Embryonic neocortical development depends on balanced production of progenitors and neurons. Genetic mutations disrupting progenitor mitosis frequently impair neurogenesis; however, the link between altered mitosis and cell fate remains poorly understood. Here we demonstrate that prolonged mitosis of radial glial progenitors directly alters neuronal fate specification and progeny viability. Live imaging of progenitors from a neurogenesis mutant, Magoh(+/-), reveals that mitotic delay significantly correlates with preferential production of neurons instead of progenitors, as well as apoptotic progeny. Independently, two pharmacological approaches reveal a causal relationship between mitotic delay and progeny fate. As mitotic duration increases, progenitors produce substantially more apoptotic progeny or neurons. We show that apoptosis, but not differentiation, is p53 dependent, demonstrating that these are distinct outcomes of mitotic delay. Together our findings reveal that prolonged mitosis is sufficient to alter fates of radial glia progeny and define a new paradigm to understand how mitosis perturbations underlie brain size disorders such as microcephaly. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Aging differentially affects male and female neural stem cell neurogenic properties

Directory of Open Access Journals (Sweden)

Jay Waldron

2010-09-01

Full Text Available Jay Waldron1, Althea McCourty1, Laurent Lecanu1,21The Research Institute of the McGill University Health Centre, Montreal, Canada; 2Department of Medicine, McGill University, Montreal, Quebec, CanadaPurpose: Neural stem cell transplantation as a brain repair strategy is a very promising technology. However, despite many attempts, the clinical success remains very deceiving. Despite clear evidence that sexual dimorphism rules many aspects of human biology, the occurrence of a sex difference in neural stem cell biology is largely understudied. Herein, we propose to determine whether gender is a dimension that drives the fate of neural stem cells through aging. Should it occur, we believe that neural stem cell sexual dimorphism and its variation during aging should be taken into account to refine clinical approaches of brain repair strategies.Methods: Neural stem cells were isolated from the subventricular zone of three- and 20-month-old male and female Long-Evans rats. Expression of the estrogen receptors, ERα and ERβ, progesterone receptor, androgen receptor, and glucocorticoid receptor was analyzed and quantified by Western blotting on undifferentiated neural stem cells. A second set of neural stem cells was treated with retinoic acid to trigger differentiation, and the expression of neuronal, astroglial, and oligodendroglial markers was determined using Western blotting.Conclusion: We provided in vitro evidence that the fate of neural stem cells is affected by sex and aging. Indeed, young male neural stem cells mainly expressed markers of neuronal and oligodendroglial fate, whereas young female neural stem cells underwent differentiation towards an astroglial phenotype. Aging resulted in a lessened capacity to express neuron and astrocyte markers. Undifferentiated neural stem cells displayed sexual dimorphism in the expression of steroid receptors, in particular ERα and ERβ, and the expression level of several steroid receptors increased

Neural convergence for language comprehension and grammatical class production in highly proficient bilinguals is independent of age of acquisition.

Science.gov (United States)

Consonni, Monica; Cafiero, Riccardo; Marin, Dario; Tettamanti, Marco; Iadanza, Antonella; Fabbro, Franco; Perani, Daniela

2013-05-01

In bilinguals, native (L1) and second (L2) languages are processed by the same neural resources that can be modulated by age of second language acquisition (AOA), proficiency level, and daily language exposure and usage. AOA seems to particularly affect grammar processing, where a complete neural convergence has been shown only in bilinguals with parallel language acquisition from birth. Despite the fact that proficiency-related neuroanatomical differences have been well documented in language comprehension (LC) and production, few reports have addressed the influence of language exposure. A still unanswered question pertains to the role of AOA, when proficiency is comparably high across languages, with respect to its modulator effects both on LC and production. Here, we evaluated with fMRI during sentence comprehension and verb and noun production tasks, two groups of highly proficient bilinguals only differing in AOA. One group learned Italian and Friulian in parallel from birth, whereas the second group learned Italian between 3 and 6 years. All participants were highly exposed to both languages, but more to Italian than Friulian. The results indicate a complete overlap of neural activations for the comprehension of both languages, not only in bilinguals from birth, but also in late bilinguals. A slightly extra activation in the left thalamus for the less-exposed language confirms that exposure may affect language processing. Noteworthy, we report for the first time that, when proficiency and exposure are kept high, noun and verb production recruit the same neural networks for L1 and L2, independently of AOA. These results support the neural convergence hypothesis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Artificial neural network prediction of ischemic tissue fate in acute stroke imaging

Science.gov (United States)

Huang, Shiliang; Shen, Qiang; Duong, Timothy Q

2010-01-01

Multimodal magnetic resonance imaging of acute stroke provides predictive value that can be used to guide stroke therapy. A flexible artificial neural network (ANN) algorithm was developed and applied to predict ischemic tissue fate on three stroke groups: 30-, 60-minute, and permanent middle cerebral artery occlusion in rats. Cerebral blood flow (CBF), apparent diffusion coefficient (ADC), and spin–spin relaxation time constant (T2) were acquired during the acute phase up to 3 hours and again at 24 hours followed by histology. Infarct was predicted on a pixel-by-pixel basis using only acute (30-minute) stroke data. In addition, neighboring pixel information and infarction incidence were also incorporated into the ANN model to improve prediction accuracy. Receiver-operating characteristic analysis was used to quantify prediction accuracy. The major findings were the following: (1) CBF alone poorly predicted the final infarct across three experimental groups; (2) ADC alone adequately predicted the infarct; (3) CBF+ADC improved the prediction accuracy; (4) inclusion of neighboring pixel information and infarction incidence further improved the prediction accuracy; and (5) prediction was more accurate for permanent occlusion, followed by 60- and 30-minute occlusion. The ANN predictive model could thus provide a flexible and objective framework for clinicians to evaluate stroke treatment options on an individual patient basis. PMID:20424631

SOXE neofunctionalization and elaboration of the neural crest during chordate evolution

Science.gov (United States)

Tai, Andrew; Cheung, Martin; Huang, Yong-Heng; Jauch, Ralf; Bronner, Marianne E.; Cheah, Kathryn S. E.

2016-01-01

During chordate evolution, two genome-wide duplications facilitated acquisition of vertebrate traits, including emergence of neural crest cells (NCCs), in which neofunctionalization of the duplicated genes are thought to have facilitated development of craniofacial structures and the peripheral nervous system. How these duplicated genes evolve and acquire the ability to specify NC and their derivatives are largely unknown. Vertebrate SoxE paralogues, most notably Sox9/10, are essential for NC induction, delamination and lineage specification. In contrast, the basal chordate, amphioxus, has a single SoxE gene and lacks NC-like cells. Here, we test the hypothesis that duplication and divergence of an ancestral SoxE gene may have facilitated elaboration of NC lineages. By using an in vivo expression assay to compare effects of AmphiSoxE and vertebrate Sox9 on NC development, we demonstrate that all SOXE proteins possess similar DNA binding and homodimerization properties and can induce NCCs. However, AmphiSOXE is less efficient than SOX9 in transactivation activity and in the ability to preferentially promote glial over neuronal fate, a difference that lies within the combined properties of amino terminal and transactivation domains. We propose that acquisition of AmphiSoxE expression in the neural plate border led to NCC emergence while duplication and divergence produced advantageous mutations in vertebrate homologues, promoting elaboration of NC traits. PMID:27734831

Glucocorticoid regulation of astrocytic fate and function.

Directory of Open Access Journals (Sweden)

Shuang Yu

Full Text Available Glial loss in the hippocampus has been suggested as a factor in the pathogenesis of stress-related brain disorders that are characterized by dysregulated glucocorticoid (GC secretion. However, little is known about the regulation of astrocytic fate by GC. Here, we show that astrocytes derived from the rat hippocampus undergo growth inhibition and display moderate activation of caspase 3 after exposure to GC. Importantly, the latter event, observed both in situ and in primary astrocytic cultures is not followed by either early- or late-stage apoptosis, as monitored by stage I or stage II DNA fragmentation. Thus, unlike hippocampal granule neurons, astrocytes are resistant to GC-induced apoptosis; this resistance is due to lower production of reactive oxygen species (ROS and a greater buffering capacity against the cytotoxic actions of ROS. We also show that GC influence hippocampal cell fate by inducing the expression of astrocyte-derived growth factors implicated in the control of neural precursor cell proliferation. Together, our results suggest that GC instigate a hitherto unknown dialog between astrocytes and neural progenitors, adding a new facet to understanding how GC influence the cytoarchitecture of the hippocampus.

Ascorbic acid alters cell fate commitment of human neural progenitors in a WNT/β-catenin/ROS signaling dependent manner.

Science.gov (United States)

Rharass, Tareck; Lantow, Margareta; Gbankoto, Adam; Weiss, Dieter G; Panáková, Daniela; Lucas, Stéphanie

2017-10-16

Improving the neuronal yield from in vitro cultivated neural progenitor cells (NPCs) is an essential challenge in transplantation therapy in neurological disorders. In this regard, Ascorbic acid (AA) is widely used to expand neurogenesis from NPCs in cultures although the mechanisms of its action remain unclear. Neurogenesis from NPCs is regulated by the redox-sensitive WNT/β-catenin signaling pathway. We therefore aimed to investigate how AA interacts with this pathway and potentiates neurogenesis. Effects of 200 μM AA were compared with the pro-neurogenic reagent and WNT/β-catenin signaling agonist lithium chloride (LiCl), and molecules with antioxidant activities i.e. N-acetyl-L-cysteine (NAC) and ruthenium red (RuR), in differentiating neural progenitor ReNcell VM cells. Cells were supplemented with reagents for two periods of treatment: a full period encompassing the whole differentiation process versus an early short period that is restricted to the cell fate commitment stage. Intracellular redox balance and reactive oxygen species (ROS) metabolism were examined by flow cytometry using redox and ROS sensors. Confocal microscopy was performed to assess cell viability, neuronal yield, and levels of two proteins: Nucleoredoxin (NXN) and the WNT/β-catenin signaling component Dishevelled 2 (DVL2). TUBB3 and MYC gene responses were evaluated by quantitative real-time PCR. DVL2-NXN complex dissociation was measured by fluorescence resonance energy transfer (FRET). In contrast to NAC which predictably exhibited an antioxidant effect, AA treatment enhanced ROS metabolism with no cytotoxic induction. Both drugs altered ROS levels only at the early stage of the differentiation as no changes were held beyond the neuronal fate commitment stage. FRET studies showed that AA treatment accelerated the redox-dependent release of the initial pool of DVL2 from its sequestration by NXN, while RuR treatment hampered the dissociation of the two proteins. Accordingly, AA

Multiphoton minimal inertia scanning for fast acquisition of neural activity signals

Science.gov (United States)

Schuck, Renaud; Go, Mary Ann; Garasto, Stefania; Reynolds, Stephanie; Dragotti, Pier Luigi; Schultz, Simon R.

2018-04-01

Objective. Multi-photon laser scanning microscopy provides a powerful tool for monitoring the spatiotemporal dynamics of neural circuit activity. It is, however, intrinsically a point scanning technique. Standard raster scanning enables imaging at subcellular resolution; however, acquisition rates are limited by the size of the field of view to be scanned. Recently developed scanning strategies such as travelling salesman scanning (TSS) have been developed to maximize cellular sampling rate by scanning only select regions in the field of view corresponding to locations of interest such as somata. However, such strategies are not optimized for the mechanical properties of galvanometric scanners. We thus aimed to develop a new scanning algorithm which produces minimal inertia trajectories, and compare its performance with existing scanning algorithms. Approach. We describe here the adaptive spiral scanning (SSA) algorithm, which fits a set of near-circular trajectories to the cellular distribution to avoid inertial drifts of galvanometer position. We compare its performance to raster scanning and TSS in terms of cellular sampling frequency and signal-to-noise ratio (SNR). Main Results. Using surrogate neuron spatial position data, we show that SSA acquisition rates are an order of magnitude higher than those for raster scanning and generally exceed those achieved by TSS for neural densities comparable with those found in the cortex. We show that this result also holds true for in vitro hippocampal mouse brain slices bath loaded with the synthetic calcium dye Cal-520 AM. The ability of TSS to ‘park’ the laser on each neuron along the scanning trajectory, however, enables higher SNR than SSA when all targets are precisely scanned. Raster scanning has the highest SNR but at a substantial cost in number of cells scanned. To understand the impact of sampling rate and SNR on functional calcium imaging, we used the Cramér-Rao Bound on evoked calcium traces recorded

FoxA4 favours notochord formation by inhibiting contiguous mesodermal fates and restricts anterior neural development in Xenopus embryos.

Science.gov (United States)

Murgan, Sabrina; Castro Colabianchi, Aitana Manuela; Monti, Renato José; Boyadjián López, Laura Elena; Aguirre, Cecilia E; Stivala, Ernesto González; Carrasco, Andrés E; López, Silvia L

2014-01-01

In vertebrates, the embryonic dorsal midline is a crucial signalling centre that patterns the surrounding tissues during development. Members of the FoxA subfamily of transcription factors are expressed in the structures that compose this centre. Foxa2 is essential for dorsal midline development in mammals, since knock-out mouse embryos lack a definitive node, notochord and floor plate. The related gene foxA4 is only present in amphibians. Expression begins in the blastula -chordin and -noggin expressing centre (BCNE) and is later restricted to the dorsal midline derivatives of the Spemann's organiser. It was suggested that the early functions of mammalian foxa2 are carried out by foxA4 in frogs, but functional experiments were needed to test this hypothesis. Here, we show that some important dorsal midline functions of mammalian foxa2 are exerted by foxA4 in Xenopus. We provide new evidence that the latter prevents the respecification of dorsal midline precursors towards contiguous fates, inhibiting prechordal and paraxial mesoderm development in favour of the notochord. In addition, we show that foxA4 is required for the correct regionalisation and maintenance of the central nervous system. FoxA4 participates in constraining the prospective rostral forebrain territory during neural specification and is necessary for the correct segregation of the most anterior ectodermal derivatives, such as the cement gland and the pituitary anlagen. Moreover, the early expression of foxA4 in the BCNE (which contains precursors of the whole forebrain and most of the midbrain and hindbrain) is directly required to restrict anterior neural development.

Exploiting Heparan Sulfate Proteoglycans in Human Neurogenesis—Controlling Lineage Specification and Fate

Directory of Open Access Journals (Sweden)

Chieh Yu

2017-10-01

Full Text Available Unspecialized, self-renewing stem cells have extraordinary application to regenerative medicine due to their multilineage differentiation potential. Stem cell therapies through replenishing damaged or lost cells in the injured area is an attractive treatment of brain trauma and neurodegenerative neurological disorders. Several stem cell types have neurogenic potential including neural stem cells (NSCs, embryonic stem cells (ESCs, induced pluripotent stem cells (iPSCs, and mesenchymal stem cells (MSCs. Currently, effective use of these cells is limited by our lack of understanding and ability to direct lineage commitment and differentiation of neural lineages. Heparan sulfate proteoglycans (HSPGs are ubiquitous proteins within the stem cell microenvironment or niche and are found localized on the cell surface and in the extracellular matrix (ECM, where they interact with numerous signaling molecules. The glycosaminoglycan (GAG chains carried by HSPGs are heterogeneous carbohydrates comprised of repeating disaccharides with specific sulfation patterns that govern ligand interactions to numerous factors including the fibroblast growth factors (FGFs and wingless-type MMTV integration site family (Wnts. As such, HSPGs are plausible targets for guiding and controlling neural stem cell lineage fate. In this review, we provide an overview of HSPG family members syndecans and glypicans, and perlecan and their role in neurogenesis. We summarize the structural changes and subsequent functional implications of heparan sulfate as cells undergo neural lineage differentiation as well as outline the role of HSPG core protein expression throughout mammalian neural development and their function as cell receptors and co-receptors. Finally, we highlight suitable biomimetic approaches for exploiting the role of HSPGs in mammalian neurogenesis to control and tailor cell differentiation into specific lineages. An improved ability to control stem cell specific neural

BMP signaling protects telencephalic fate by repressing eye identity and its Cxcr4-dependent morphogenesis.

Science.gov (United States)

Bielen, Holger; Houart, Corinne

2012-10-16

Depletion of Wnt signaling is a major requirement for the induction of the anterior prosencephalon. However, the molecular events driving the differential regionalization of this area into eye-field and telencephalon fates are still unknown. Here we show that the BMP pathway is active in the anterior neural ectoderm during late blastula to early gastrula stage in zebrafish. Bmp2b mutants and mosaic loss-of-function experiments reveal that BMP acts as a repressor of eye-field fate through inhibition of its key transcription factor Rx3, thereby protecting the future telencephalon from acquiring eye identity. This BMP-driven mechanism initiates the establishment of the telencephalon prior to the involvement of Wnt antagonists from the anterior neural border. Furthermore, we demonstrate that Rx3 and BMP are respectively required to maintain and restrict the chemokine receptor cxcr4a, which in turn contributes to the morphogenetic separation of eye-field and telencephalic cells during early neurulation. Copyright © 2012 Elsevier Inc. All rights reserved.

Natural language acquisition in large scale neural semantic networks

Science.gov (United States)

Ealey, Douglas

This thesis puts forward the view that a purely signal- based approach to natural language processing is both plausible and desirable. By questioning the veracity of symbolic representations of meaning, it argues for a unified, non-symbolic model of knowledge representation that is both biologically plausible and, potentially, highly efficient. Processes to generate a grounded, neural form of this model-dubbed the semantic filter-are discussed. The combined effects of local neural organisation, coincident with perceptual maturation, are used to hypothesise its nature. This theoretical model is then validated in light of a number of fundamental neurological constraints and milestones. The mechanisms of semantic and episodic development that the model predicts are then used to explain linguistic properties, such as propositions and verbs, syntax and scripting. To mimic the growth of locally densely connected structures upon an unbounded neural substrate, a system is developed that can grow arbitrarily large, data- dependant structures composed of individual self- organising neural networks. The maturational nature of the data used results in a structure in which the perception of concepts is refined by the networks, but demarcated by subsequent structure. As a consequence, the overall structure shows significant memory and computational benefits, as predicted by the cognitive and neural models. Furthermore, the localised nature of the neural architecture also avoids the increasing error sensitivity and redundancy of traditional systems as the training domain grows. The semantic and episodic filters have been demonstrated to perform as well, or better, than more specialist networks, whilst using significantly larger vocabularies, more complex sentence forms and more natural corpora.

In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus

Science.gov (United States)

Suh, Hoonkyo; Consiglio, Antonella; Ray, Jasodhara; Sawai, Toru; D'Amour, Kevin A.; Gage, Fred H.

2007-01-01

Summary To characterize the properties of adult neural stem cells (NSCs), we generated and analyzed Sox2-GFP transgenic mice. Sox2-GFP cells in the subgranular zone (SGZ) express markers specific for progenitors, but they represent two morphologically distinct populations that differ in proliferation levels. Lentivirus- and retrovirus-mediated fate tracing studies showed that Sox2+ cells in the SGZ have potential to give rise to neurons and astrocytes, revealing their multipotency at the population as well as a single cell level. More interestingly, a subpopulation of Sox2+ cells gives rise to cells that retain Sox2, highlighting Sox2+ cells as a primary source for adult NSCs. In response to mitotic signals, increased proliferation of Sox2+ cells is coupled with the generation of Sox2+ NSCs as well as neuronal precursors. An asymmetric contribution of Sox2+ NSCs may play an important role in maintaining the constant size of the NSC pool and producing newly born neurons during adult neurogenesis. PMID:18371391

Neural crest cells: from developmental biology to clinical interventions.

Science.gov (United States)

Noisa, Parinya; Raivio, Taneli

2014-09-01

Neural crest cells are multipotent cells, which are specified in embryonic ectoderm in the border of neural plate and epiderm during early development by interconnection of extrinsic stimuli and intrinsic factors. Neural crest cells are capable of differentiating into various somatic cell types, including melanocytes, craniofacial cartilage and bone, smooth muscle, and peripheral nervous cells, which supports their promise for cell therapy. In this work, we provide a comprehensive review of wide aspects of neural crest cells from their developmental biology to applicability in medical research. We provide a simplified model of neural crest cell development and highlight the key external stimuli and intrinsic regulators that determine the neural crest cell fate. Defects of neural crest cell development leading to several human disorders are also mentioned, with the emphasis of using human induced pluripotent stem cells to model neurocristopathic syndromes. © 2014 Wiley Periodicals, Inc.

Examining neural correlates of skill acquisition in a complex videogame training program.

Science.gov (United States)

Prakash, Ruchika S; De Leon, Angeline A; Mourany, Lyla; Lee, Hyunkyu; Voss, Michelle W; Boot, Walter R; Basak, Chandramallika; Fabiani, Monica; Gratton, Gabriele; Kramer, Arthur F

2012-01-01

Acquisition of complex skills is a universal feature of human behavior that has been conceptualized as a process that starts with intense resource dependency, requires effortful cognitive control, and ends in relative automaticity on the multi-faceted task. The present study examined the effects of different theoretically based training strategies on cortical recruitment during acquisition of complex video game skills. Seventy-five participants were recruited and assigned to one of three training groups: (1) Fixed Emphasis Training (FET), in which participants practiced the game, (2) Hybrid Variable-Priority Training (HVT), in which participants practiced using a combination of part-task training and variable priority training, or (3) a Control group that received limited game play. After 30 h of training, game data indicated a significant advantage for the two training groups relative to the control group. The HVT group demonstrated enhanced benefits of training, as indexed by an improvement in overall game score and a reduction in cortical recruitment post-training. Specifically, while both groups demonstrated a significant reduction of activation in attentional control areas, namely the right middle frontal gyrus, right superior frontal gyrus, and the ventral medial prefrontal cortex, participants in the control group continued to engage these areas post-training, suggesting a sustained reliance on attentional regions during challenging task demands. The HVT group showed a further reduction in neural resources post-training compared to the FET group in these cognitive control regions, along with reduced activation in the motor and sensory cortices and the posteromedial cortex. Findings suggest that training, specifically one that emphasizes cognitive flexibility can reduce the attentional demands of a complex cognitive task, along with reduced reliance on the motor network.

Examining neural correlates of skill acquisition in a complex videogame training program

Directory of Open Access Journals (Sweden)

Ruchika S Prakash

2012-05-01

Full Text Available Acquisition of complex skills is a universal feature of human behavior that has been conceptualized as a process that starts with intense resource dependency, requires effortful cognitive control, and ends in relative automaticity on the multi-faceted task. The present study examined the effects of different theoretically-based training strategies on cortical recruitment during acquisition of complex videogame skills. Seventy-five participants were recruited and assigned to one of three training groups: Fixed Emphasis Training (FET, in which participants practiced the game, Hybrid Variable Priority Training (HVT, in which participants practiced using a combination of part-task training and variable priority training, or a Control group that received limited game play. After 30 hours of training, game data indicated a significant advantage for the two training groups relative to the control group. The HVT group demonstrated enhanced benefits of training, as indexed by an improvement in overall game score and a reduction in cortical recruitment post-training. Specifically, while both groups demonstrated a significant reduction of activation in attentional control areas, namely the right middle frontal gyrus, right superior frontal gyrus, and the ventral medial prefrontal cortex, participants in the control group continued to engage these areas post-training, suggesting a sustained reliance on attentional regions during challenging task demands. The HVT group showed a further reduction in neural resources post-training compared to the FET group in these cognitive control regions, along with reduced activation in the motor and sensory cortices and the posteromedial cortex. Findings suggest that training, specifically one that emphasizes cognitive flexibility can reduce the attentional demands of a complex cognitive task, along with reduced reliance on the motor network.

FoxA4 favours notochord formation by inhibiting contiguous mesodermal fates and restricts anterior neural development in Xenopus embryos.

Directory of Open Access Journals (Sweden)

Sabrina Murgan

Full Text Available In vertebrates, the embryonic dorsal midline is a crucial signalling centre that patterns the surrounding tissues during development. Members of the FoxA subfamily of transcription factors are expressed in the structures that compose this centre. Foxa2 is essential for dorsal midline development in mammals, since knock-out mouse embryos lack a definitive node, notochord and floor plate. The related gene foxA4 is only present in amphibians. Expression begins in the blastula -chordin and -noggin expressing centre (BCNE and is later restricted to the dorsal midline derivatives of the Spemann's organiser. It was suggested that the early functions of mammalian foxa2 are carried out by foxA4 in frogs, but functional experiments were needed to test this hypothesis. Here, we show that some important dorsal midline functions of mammalian foxa2 are exerted by foxA4 in Xenopus. We provide new evidence that the latter prevents the respecification of dorsal midline precursors towards contiguous fates, inhibiting prechordal and paraxial mesoderm development in favour of the notochord. In addition, we show that foxA4 is required for the correct regionalisation and maintenance of the central nervous system. FoxA4 participates in constraining the prospective rostral forebrain territory during neural specification and is necessary for the correct segregation of the most anterior ectodermal derivatives, such as the cement gland and the pituitary anlagen. Moreover, the early expression of foxA4 in the BCNE (which contains precursors of the whole forebrain and most of the midbrain and hindbrain is directly required to restrict anterior neural development.

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.

Prion replication occurs in endogenous adult neural stem cells and alters their neuronal fate: involvement of endogenous neural stem cells in prion diseases.

Directory of Open Access Journals (Sweden)

Aroa Relaño-Ginès

Full Text Available Prion diseases are irreversible progressive neurodegenerative diseases, leading to severe incapacity and death. They are characterized in the brain by prion amyloid deposits, vacuolisation, astrocytosis, neuronal degeneration, and by cognitive, behavioural and physical impairments. There is no treatment for these disorders and stem cell therapy therefore represents an interesting new approach. Gains could not only result from the cell transplantation, but also from the stimulation of endogenous neural stem cells (NSC or by the combination of both approaches. However, the development of such strategies requires a detailed knowledge of the pathology, particularly concerning the status of the adult neurogenesis and endogenous NSC during the development of the disease. During the past decade, several studies have consistently shown that NSC reside in the adult mammalian central nervous system (CNS and that adult neurogenesis occurs throughout the adulthood in the subventricular zone of the lateral ventricle or the Dentate Gyrus of the hippocampus. Adult NSC are believed to constitute a reservoir for neuronal replacement during normal cell turnover or after brain injury. However, the activation of this system does not fully compensate the neuronal loss that occurs during neurodegenerative diseases and could even contribute to the disease progression. We investigated here the status of these cells during the development of prion disorders. We were able to show that NSC accumulate and replicate prions. Importantly, this resulted in the alteration of their neuronal fate which then represents a new pathologic event that might underlie the rapid progression of the disease.

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.

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...

Spatio-temporal Model of Endogenous ROS and Raft-Dependent WNT/Beta-Catenin Signaling Driving Cell Fate Commitment in Human Neural Progenitor Cells

Science.gov (United States)

Haack, Fiete; Lemcke, Heiko; Ewald, Roland; Rharass, Tareck; Uhrmacher, Adelinde M.

2015-01-01

Canonical WNT/β-catenin signaling is a central pathway in embryonic development, but it is also connected to a number of cancers and developmental disorders. Here we apply a combined in-vitro and in-silico approach to investigate the spatio-temporal regulation of WNT/β-catenin signaling during the early neural differentiation process of human neural progenitors cells (hNPCs), which form a new prospect for replacement therapies in the context of neurodegenerative diseases. Experimental measurements indicate a second signal mechanism, in addition to canonical WNT signaling, being involved in the regulation of nuclear β-catenin levels during the cell fate commitment phase of neural differentiation. We find that the biphasic activation of β-catenin signaling observed experimentally can only be explained through a model that combines Reactive Oxygen Species (ROS) and raft dependent WNT/β-catenin signaling. Accordingly after initiation of differentiation endogenous ROS activates DVL in a redox-dependent manner leading to a transient activation of down-stream β-catenin signaling, followed by continuous auto/paracrine WNT signaling, which crucially depends on lipid rafts. Our simulation studies further illustrate the elaborate spatio-temporal regulation of DVL, which, depending on its concentration and localization, may either act as direct inducer of the transient ROS/β-catenin signal or as amplifier during continuous auto-/parcrine WNT/β-catenin signaling. In addition we provide the first stochastic computational model of WNT/β-catenin signaling that combines membrane-related and intracellular processes, including lipid rafts/receptor dynamics as well as WNT- and ROS-dependent β-catenin activation. The model’s predictive ability is demonstrated under a wide range of varying conditions for in-vitro and in-silico reference data sets. Our in-silico approach is realized in a multi-level rule-based language, that facilitates the extension and modification of the

Scandinavian belief in fate

Directory of Open Access Journals (Sweden)

Åke Ström

1967-02-01

Full Text Available In point of principle, Christianity does not give room for any belief in fate. Astrology, horoscopes, divination, etc., are strictly rejected. Belief in fate never disappeared in Christian countries, nor did it in Scandinavia in Christian times. Especially in folklore we can find it at any period: People believed in an implacable fate. All folklore is filled up with this belief in destiny. Nobody can escape his fate. The future lies in the hands of fate, and the time to come takes its form according to inscrutable laws. The pre-Christian period in Scandinavia, dominated by pagan Norse religion, and the secularized epoch of the 20th century, however, show more distinctive and more widespread beliefs in fate than does the Christian period. The present paper makes a comparison between these forms of belief.

Retrovirally transduced NCAM140 facilitates neuronal fate choice of hippocampal progenitor cells.

Science.gov (United States)

Kim, Ju Hee; Lee, Jung-Ha; Park, Jin-Yong; Park, Chang-Hwan; Yun, Chae-Ok; Lee, Sang-Hun; Lee, Yong-Sung; Son, Hyeon

2005-07-01

Neural cell adhesion molecule (NCAM) influences proliferation and differentiation of neuronal cells. However, only a little is known about the downstream effects of NCAM signalling, such as alterations in gene transcription, which are associated with cell fate choice. To examine whether NCAM plays a role in cell fate choice during hippocampal neurogenesis, we performed a gain-of-function study, using a retroviral vector which contained full-length NCAM140 cDNA and the marker gene EGFP, and found that NCAM140 promoted neurogenesis by activating proneural transcription activators with concurrent inhibition of gliogenesis. The enhanced transcript levels of proneural transcription factors in NCAM140-transduced cells were down-regulated by treatment of the cells with mitogen-activated protein kinase kinase (MEK) inhibitor PD098059. Overall, these findings suggest that NCAM140 may facilitate hippocampal neurogenesis via regulation of proneurogenic transcription factors in an extracellular signal-regulated kinase (ERK)-dependent manner.

Neural stem cell heterogeneity through time and space in the ventricular-subventricular zone.

Science.gov (United States)

Rushing, Gabrielle; Ihrie, Rebecca A

2016-08-01

The origin and classification of neural stem cells (NSCs) has been a subject of intense investigation for the past two decades. Efforts to categorize NSCs based on their location, function and expression have established that these cells are a heterogeneous pool in both the embryonic and adult brain. The discovery and additional characterization of adult NSCs has introduced the possibility of using these cells as a source for neuronal and glial replacement following injury or disease. To understand how one could manipulate NSC developmental programs for therapeutic use, additional work is needed to elucidate how NSCs are programmed and how signals during development are interpreted to determine cell fate. This review describes the identification, classification and characterization of NSCs within the large neurogenic niche of the ventricular-subventricular zone (V-SVZ). A literature search was conducted using Pubmed including the keywords "ventricular-subventricular zone," "neural stem cell," "heterogeneity," "identity" and/or "single cell" to find relevant manuscripts to include within the review. A special focus was placed on more recent findings using single-cell level analyses on neural stem cells within their niche(s). This review discusses over 20 research articles detailing findings on V-SVZ NSC heterogeneity, over 25 articles describing fate determinants of NSCs, and focuses on 8 recent publications using distinct single-cell analyses of neural stem cells including flow cytometry and RNA-seq. Additionally, over 60 manuscripts highlighting the markers expressed on cells within the NSC lineage are included in a chart divided by cell type. Investigation of NSC heterogeneity and fate decisions is ongoing. Thus far, much research has been conducted in mice however, findings in human and other mammalian species are also discussed here. Implications of NSC heterogeneity established in the embryo for the properties of NSCs in the adult brain are explored, including

Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined Conditions

Directory of Open Access Journals (Sweden)

Agnete Kirkeby

2012-06-01

Full Text Available To model human neural-cell-fate specification and to provide cells for regenerative therapies, we have developed a method to generate human neural progenitors and neurons from human embryonic stem cells, which recapitulates human fetal brain development. Through the addition of a small molecule that activates canonical WNT signaling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. Ten days after initiation of differentiation, the progenitors could be transplanted to the adult rat striatum, where they formed neuron-rich and tumor-free grafts with maintained regional specification. Cells patterned toward a ventral midbrain (VM identity generated a high proportion of authentic dopaminergic neurons after transplantation. The dopamine neurons showed morphology, projection pattern, and protein expression identical to that of human fetal VM cells grafted in parallel. VM-patterned but not forebrain-patterned neurons released dopamine and reversed motor deficits in an animal model of Parkinson's disease.

Chromatin Remodeling BAF (SWI/SNF Complexes in Neural Development and Disorders

Directory of Open Access Journals (Sweden)

Godwin Sokpor

2017-08-01

Full Text Available The ATP-dependent BRG1/BRM associated factor (BAF chromatin remodeling complexes are crucial in regulating gene expression by controlling chromatin dynamics. Over the last decade, it has become increasingly clear that during neural development in mammals, distinct ontogenetic stage-specific BAF complexes derived from combinatorial assembly of their subunits are formed in neural progenitors and post-mitotic neural cells. Proper functioning of the BAF complexes plays critical roles in neural development, including the establishment and maintenance of neural fates and functionality. Indeed, recent human exome sequencing and genome-wide association studies have revealed that mutations in BAF complex subunits are linked to neurodevelopmental disorders such as Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, Kleefstra's syndrome spectrum, Hirschsprung's disease, autism spectrum disorder, and schizophrenia. In this review, we focus on the latest insights into the functions of BAF complexes during neural development and the plausible mechanistic basis of how mutations in known BAF subunits are associated with certain neurodevelopmental disorders.

Chromatin Remodeling BAF (SWI/SNF) Complexes in Neural Development and Disorders

Science.gov (United States)

Sokpor, Godwin; Xie, Yuanbin; Rosenbusch, Joachim; Tuoc, Tran

2017-01-01

The ATP-dependent BRG1/BRM associated factor (BAF) chromatin remodeling complexes are crucial in regulating gene expression by controlling chromatin dynamics. Over the last decade, it has become increasingly clear that during neural development in mammals, distinct ontogenetic stage-specific BAF complexes derived from combinatorial assembly of their subunits are formed in neural progenitors and post-mitotic neural cells. Proper functioning of the BAF complexes plays critical roles in neural development, including the establishment and maintenance of neural fates and functionality. Indeed, recent human exome sequencing and genome-wide association studies have revealed that mutations in BAF complex subunits are linked to neurodevelopmental disorders such as Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, Kleefstra's syndrome spectrum, Hirschsprung's disease, autism spectrum disorder, and schizophrenia. In this review, we focus on the latest insights into the functions of BAF complexes during neural development and the plausible mechanistic basis of how mutations in known BAF subunits are associated with certain neurodevelopmental disorders. PMID:28824374

Chromatin Remodeling BAF (SWI/SNF) Complexes in Neural Development and Disorders.

Science.gov (United States)

Sokpor, Godwin; Xie, Yuanbin; Rosenbusch, Joachim; Tuoc, Tran

2017-01-01

The ATP-dependent BRG1/BRM associated factor (BAF) chromatin remodeling complexes are crucial in regulating gene expression by controlling chromatin dynamics. Over the last decade, it has become increasingly clear that during neural development in mammals, distinct ontogenetic stage-specific BAF complexes derived from combinatorial assembly of their subunits are formed in neural progenitors and post-mitotic neural cells. Proper functioning of the BAF complexes plays critical roles in neural development, including the establishment and maintenance of neural fates and functionality. Indeed, recent human exome sequencing and genome-wide association studies have revealed that mutations in BAF complex subunits are linked to neurodevelopmental disorders such as Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, Kleefstra's syndrome spectrum, Hirschsprung's disease, autism spectrum disorder, and schizophrenia. In this review, we focus on the latest insights into the functions of BAF complexes during neural development and the plausible mechanistic basis of how mutations in known BAF subunits are associated with certain neurodevelopmental disorders.

Neural overlap in processing music and speech

Science.gov (United States)

Peretz, Isabelle; Vuvan, Dominique; Lagrois, Marie-Élaine; Armony, Jorge L.

2015-01-01

Neural overlap in processing music and speech, as measured by the co-activation of brain regions in neuroimaging studies, may suggest that parts of the neural circuitries established for language may have been recycled during evolution for musicality, or vice versa that musicality served as a springboard for language emergence. Such a perspective has important implications for several topics of general interest besides evolutionary origins. For instance, neural overlap is an important premise for the possibility of music training to influence language acquisition and literacy. However, neural overlap in processing music and speech does not entail sharing neural circuitries. Neural separability between music and speech may occur in overlapping brain regions. In this paper, we review the evidence and outline the issues faced in interpreting such neural data, and argue that converging evidence from several methodologies is needed before neural overlap is taken as evidence of sharing. PMID:25646513

Emerging trends in neuro engineering and neural computation

CERN Document Server

Lee, Kendall; Garmestani, Hamid; Lim, Chee

2017-01-01

This book focuses on neuro-engineering and neural computing, a multi-disciplinary field of research attracting considerable attention from engineers, neuroscientists, microbiologists and material scientists. It explores a range of topics concerning the design and development of innovative neural and brain interfacing technologies, as well as novel information acquisition and processing algorithms to make sense of the acquired data. The book also highlights emerging trends and advances regarding the applications of neuro-engineering in real-world scenarios, such as neural prostheses, diagnosis of neural degenerative diseases, deep brain stimulation, biosensors, real neural network-inspired artificial neural networks (ANNs) and the predictive modeling of information flows in neuronal networks. The book is broadly divided into three main sections including: current trends in technological developments, neural computation techniques to make sense of the neural behavioral data, and application of these technologie...

Neural overlap in processing music and speech.

Science.gov (United States)

Peretz, Isabelle; Vuvan, Dominique; Lagrois, Marie-Élaine; Armony, Jorge L

2015-03-19

Neural overlap in processing music and speech, as measured by the co-activation of brain regions in neuroimaging studies, may suggest that parts of the neural circuitries established for language may have been recycled during evolution for musicality, or vice versa that musicality served as a springboard for language emergence. Such a perspective has important implications for several topics of general interest besides evolutionary origins. For instance, neural overlap is an important premise for the possibility of music training to influence language acquisition and literacy. However, neural overlap in processing music and speech does not entail sharing neural circuitries. Neural separability between music and speech may occur in overlapping brain regions. In this paper, we review the evidence and outline the issues faced in interpreting such neural data, and argue that converging evidence from several methodologies is needed before neural overlap is taken as evidence of sharing. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Neural networks for event filtering at D/O/

International Nuclear Information System (INIS)

Cutts, D.; Hoftun, J.S.; Sornborger, A.; Johnson, C.R.; Zeller, R.T.

1989-01-01

Neural networks may provide important tools for pattern recognition in high energy physics. We discuss an initial exploration of these techniques, presenting the result of network simulations of several filter algorithms. The D0 data acquisition system, a MicroVAX farm, will perform critical event selection; we describe a possible implementation of neural network algorithms in this system. 7 refs., 4 figs

Neural networks, D0, and the SSC

International Nuclear Information System (INIS)

Barter, C.; Cutts, D.; Hoftun, J.S.; Partridge, R.A.; Sornborger, A.T.; Johnson, C.T.; Zeller, R.T.

1989-01-01

We outline several exploratory studies involving neural network simulations applied to pattern recognition in high energy physics. We describe the D0 data acquisition system and a natual means by which algorithms derived from neural networks techniques may be incorporated into recently developed hardware associated with the D0 MicroVAX farm nodes. Such applications to the event filtering needed by SSC detectors look interesting. 10 refs., 11 figs

Tcf7l1 protects the anterior neural fold from adopting the neural crest fate

Czech Academy of Sciences Publication Activity Database

Mašek, Jan; Machoň, Ondřej; Kořínek, Vladimír; Taketo, M.M.; Kozmik, Zbyněk

2016-01-01

Roč. 143, č. 12 (2016), s. 2206-2216 ISSN 0950-1991 R&D Projects: GA ČR GAP305/12/2042; GA ČR(CZ) GA14-33952S; GA MŠk(CZ) LK11214; GA MŠk LO1419; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : Tcf/Lef * Wnt dignaling * neural crest * forebrain * mouse * zebrafish Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.843, year: 2016

Novel perspectives of neural stem cell differentiation: from neurotransmitters to therapeutics.

Science.gov (United States)

Trujillo, Cleber A; Schwindt, Telma T; Martins, Antonio H; Alves, Janaína M; Mello, Luiz Eugênio; Ulrich, Henning

2009-01-01

In the past years, many reports have described the existence of neural progenitor and stem cells in the adult central nervous system capable of generating new neurons, astrocytes, and oligodendrocytes. This discovery has overturned the central assumption in the neuroscience field, of no new neurons being originated in the brain after birth and provided the fundaments to understand the molecular basis of neural differentiation and to develop new therapies for neural tissue repair. Although the mechanisms underlying cell fate during neural development are not yet understood, the importance of intrinsic and extrinsic factors and of an appropriate microenvironment is well known. In this context, emerging evidence strongly suggests that glial cells play a key role in controlling multiple steps of neurogenesis. Those cells, of particular radial glia, are important for migration, cell specification, and integration of neurons into a functional neural network. This review aims to present an update in the neurogenesis area and highlight the modulation of neural stem cell differentiation by neurotransmitters, growth factors, and their receptors, with possible applications for cell therapy strategies of neurological disorders.

Hydrogel formulation determines cell fate of fetal and adult neural progenitor cells

Directory of Open Access Journals (Sweden)

Emily R. Aurand

2014-01-01

Full Text Available Hydrogels provide a unique tool for neural tissue engineering. These materials can be customized for certain functions, i.e. to provide cell/drug delivery or act as a physical scaffold. Unfortunately, hydrogel complexities can negatively impact their biocompatibility, resulting in unintended consequences. These adverse effects may be combated with a better understanding of hydrogel chemical, physical, and mechanical properties, and how these properties affect encapsulated neural cells. We defined the polymerization and degradation rates and compressive moduli of 25 hydrogels formulated from different concentrations of hyaluronic acid (HA and poly(ethylene glycol (PEG. Changes in compressive modulus were driven primarily by the HA concentration. The in vitro biocompatibility of fetal-derived (fNPC and adult-derived (aNPC neural progenitor cells was dependent on hydrogel formulation. Acute survival of fNPC benefited from hydrogel encapsulation. NPC differentiation was divergent: fNPC differentiated into mostly glial cells, compared with neuronal differentiation of aNPC. Differentiation was influenced in part by the hydrogel mechanical properties. This study indicates that there can be a wide range of HA and PEG hydrogels compatible with NPC. Additionally, this is the first study comparing hydrogel encapsulation of NPC derived from different aged sources, with data suggesting that fNPC and aNPC respond dissimilarly within the same hydrogel formulation.

Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development

Directory of Open Access Journals (Sweden)

Bello Bruno C

2008-02-01

Full Text Available Abstract Background In the mammalian brain, neural stem cells divide asymmetrically and often amplify the number of progeny they generate via symmetrically dividing intermediate progenitors. Here we investigate whether specific neural stem cell-like neuroblasts in the brain of Drosophila might also amplify neuronal proliferation by generating symmetrically dividing intermediate progenitors. Results Cell lineage-tracing and genetic marker analysis show that remarkably large neuroblast lineages exist in the dorsomedial larval brain of Drosophila. These lineages are generated by brain neuroblasts that divide asymmetrically to self renew but, unlike other brain neuroblasts, do not segregate the differentiating cell fate determinant Prospero to their smaller daughter cells. These daughter cells continue to express neuroblast-specific molecular markers and divide repeatedly to produce neural progeny, demonstrating that they are proliferating intermediate progenitors. The proliferative divisions of these intermediate progenitors have novel cellular and molecular features; they are morphologically symmetrical, but molecularly asymmetrical in that key differentiating cell fate determinants are segregated into only one of the two daughter cells. Conclusion Our findings provide cellular and molecular evidence for a new mode of neurogenesis in the larval brain of Drosophila that involves the amplification of neuroblast proliferation through intermediate progenitors. This type of neurogenesis bears remarkable similarities to neurogenesis in the mammalian brain, where neural stem cells as primary progenitors amplify the number of progeny they generate through generation of secondary progenitors. This suggests that key aspects of neural stem cell biology might be conserved in brain development of insects and mammals.

An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells

Directory of Open Access Journals (Sweden)

David A. Turner

2014-06-01

Full Text Available Embryonic Stem cells derived from the epiblast tissue of the mammalian blastocyst retain the capability to differentiate into any adult cell type and are able to self-renew indefinitely under appropriate culture conditions. Despite the large amount of knowledge that we have accumulated to date about the regulation and control of self-renewal, efficient directed differentiation into specific tissues remains elusive. In this work, we have analysed in a systematic manner the interaction between the dynamics of loss of pluripotency and Activin/Nodal, BMP4 and Wnt signalling in fate assignment during the early stages of differentiation of mouse ES cells in culture. During the initial period of differentiation, cells exit from pluripotency and enter an Epi-like state. Following this transient stage, and under the influence of Activin/Nodal and BMP signalling, cells face a fate choice between differentiating into neuroectoderm and contributing to Primitive Streak fates. We find that Wnt signalling does not suppress neural development as previously thought and that it aids both fates in a context dependent manner. Our results suggest that as cells exit pluripotency they are endowed with a primary neuroectodermal fate and that the potency to become endomesodermal rises with time. We suggest that this situation translates into a “race for fates” in which the neuroectodermal fate has an advantage.

The role of BAF (mSWI/SNF) complexes in mammalian neural development.

Science.gov (United States)

Son, Esther Y; Crabtree, Gerald R

2014-09-01

The BAF (mammalian SWI/SNF) complexes are a family of multi-subunit ATP-dependent chromatin remodelers that use ATP hydrolysis to alter chromatin structure. Distinct BAF complex compositions are possible through combinatorial assembly of homologous subunit families and can serve non-redundant functions. In mammalian neural development, developmental stage-specific BAF assemblies are found in embryonic stem cells, neural progenitors and postmitotic neurons. In particular, the neural progenitor-specific BAF complexes are essential for controlling the kinetics and mode of neural progenitor cell division, while neuronal BAF function is necessary for the maturation of postmitotic neuronal phenotypes as well as long-term memory formation. The microRNA-mediated mechanism for transitioning from npBAF to nBAF complexes is instructive for the neuronal fate and can even convert fibroblasts into neurons. The high frequency of BAF subunit mutations in neurological disorders underscores the rate-determining role of BAF complexes in neural development, homeostasis, and plasticity. © 2014 Wiley Periodicals, Inc.

Notch and presenilin regulate cellular expansion and cytokine secretion but cannot instruct Th1/Th2 fate acquisition.

Directory of Open Access Journals (Sweden)

Chin-Tong Ong

2008-07-01

Full Text Available Recent reports suggested that Delta1, 4 and Jagged1, 2 possessed the ability to instruct CD4(+ T cell into selection of Th1 or Th2 fates, respectively, although the underlying mechanism endowing the cleaved Notch receptor with memory of ligand involved in its activation remains elusive. To examine this, we prepared artificial antigen-presenting cells expressing either DLL1 or Jag1. Although both ligands were efficient in inducing Notch2 cleavage and activation in CD4(+ T or reporter cells, the presence of Lunatic Fringe in CD4(+ T cells inhibited Jag1 activation of Notch1 receptor. Neither ligand could induce Th1 or Th2 fate choice independently of cytokines or redirect cytokine-driven Th1 or Th2 development. Instead, we find that Notch ligands only augment cytokine production during T cell differentiation in the presence of polarizing IL-12 and IL-4. Moreover, the differentiation choices of naïve CD4(+ T cells lacking gamma-secretase, RBP-J, or both in response to polarizing cytokines revealed that neither presenilin proteins nor RBP-J were required for cytokine-induced Th1/Th2 fate selection. However, presenilins facilitate cellular proliferation and cytokine secretion in an RBP-J (and thus, Notch independent manner. The controversies surrounding the role of Notch and presenilins in Th1/Th2 polarization may reflect their role as genetic modifiers of T-helper cells differentiation.

Neural cell fate in rca1 and cycA mutants: the roles of intrinsic and extrinsic factors in asymmetric division in the Drosophila central nervous system.

Science.gov (United States)

Lear, B C; Skeath, J B; Patel, N H

1999-11-01

In the central nervous system (CNS) of Drosophila embryos lacking regulator of cyclin A (rca1) or cyclin A, we observe that several ganglion mother cells (GMCs) fail to divide. Whereas GMCs normally produce two sibling neurons that acquire different fates ('A/B'), non-dividing GMCs differentiate exclusively in the manner of one of their progeny ('B'). In zygotic numb mutants, sibling neuron fate alterations ('A/B' to 'A/A') occur infrequently or do not occur in some sibling pairs; we have determined that depletion of both maternal and zygotic numb causes sibling neurons to acquire equalized fates ('A/A') with near-complete expressivity. In rca1, numb mutant embryos, we observe binary cell fate changes ('B' to 'A') in several GMCs as well. Finally, we have demonstrated that expression of Delta in the mesoderm is sufficient to attain both sibling fates. Our results indicate that the intrinsic determinant Numb is absolutely required to attain differential sibling neuron fates. While the extrinsic factors Notch and Delta are also required to attain both fates, our results indicate that Delta signal can be received from outside the sibling pair.

AKT signaling displays multifaceted functions in neural crest development.

Science.gov (United States)

Sittewelle, Méghane; Monsoro-Burq, Anne H

2018-05-31

AKT signaling is an essential intracellular pathway controlling cell homeostasis, cell proliferation and survival, as well as cell migration and differentiation in adults. Alterations impacting the AKT pathway are involved in many pathological conditions in human disease. Similarly, during development, multiple transmembrane molecules, such as FGF receptors, PDGF receptors or integrins, activate AKT to control embryonic cell proliferation, migration, differentiation, and also cell fate decisions. While many studies in mouse embryos have clearly implicated AKT signaling in the differentiation of several neural crest derivatives, information on AKT functions during the earliest steps of neural crest development had remained relatively scarce until recently. However, recent studies on known and novel regulators of AKT signaling demonstrate that this pathway plays critical roles throughout the development of neural crest progenitors. Non-mammalian models such as fish and frog embryos have been instrumental to our understanding of AKT functions in neural crest development, both in neural crest progenitors and in the neighboring tissues. This review combines current knowledge acquired from all these different vertebrate animal models to describe the various roles of AKT signaling related to neural crest development in vivo. We first describe the importance of AKT signaling in patterning the tissues involved in neural crest induction, namely the dorsal mesoderm and the ectoderm. We then focus on AKT signaling functions in neural crest migration and differentiation. Copyright © 2018 Elsevier Inc. All rights reserved.

Learning and adaptation: neural and behavioural mechanisms behind behaviour change

Science.gov (United States)

Lowe, Robert; Sandamirskaya, Yulia

2018-01-01

This special issue presents perspectives on learning and adaptation as they apply to a number of cognitive phenomena including pupil dilation in humans and attention in robots, natural language acquisition and production in embodied agents (robots), human-robot game play and social interaction, neural-dynamic modelling of active perception and neural-dynamic modelling of infant development in the Piagetian A-not-B task. The aim of the special issue, through its contributions, is to highlight some of the critical neural-dynamic and behavioural aspects of learning as it grounds adaptive responses in robotic- and neural-dynamic systems.

Novel insights into the role of NF-κB p50 in astrocyte-mediated fate specification of adult neural progenitor cells

Directory of Open Access Journals (Sweden)

Valeria Bortolotto

2017-01-01

Full Text Available Within the CNS nuclear factor-kappa B (NF-κB transcription factors are involved in a wide range of functions both in homeostasis and in pathology. Over the years, our and other groups produced a vast array of information on the complex involvement of NF-κB proteins in different aspects of postnatal neurogenesis. In particular, several extracellular signals and membrane receptors have been identified as being able to affect neural progenitor cells (NPC and their progeny via NF-κB activation. A crucial role in the regulation of neuronal fate specification in adult hippocampal NPC is played by the NF-κB p50 subunit. NF-κB p50KO mice display a remarkable reduction in adult hippocampal neurogenesis which correlates with a selective defect in hippocampal-dependent short-term memory. Moreover absence of NF-κB p50 can profoundly affect the in vitro proneurogenic response of adult hippocampal NPC (ahNPC to several endogenous signals and drugs. Herein we briefly review the current knowledge on the pivotal role of NF-κB p50 in the regulation of adult hippocampal neurogenesis. In addition we discuss more recent data that further extend the relevance of NF-κB p50 to novel astroglia-derived signals which can influence neuronal specification of ahNPC and to astrocyte-NPC cross-talk.

hESC Differentiation toward an Autonomic Neuronal Cell Fate Depends on Distinct Cues from the Co-Patterning Vasculature

Directory of Open Access Journals (Sweden)

Lisette M. Acevedo

2015-06-01

Full Text Available To gain insight into the cellular and molecular cues that promote neurovascular co-patterning at the earliest stages of human embryogenesis, we developed a human embryonic stem cell model to mimic the developing epiblast. Contact of ectoderm-derived neural cells with mesoderm-derived vasculature is initiated via the neural crest (NC, not the neural tube (NT. Neurovascular co-patterning then ensues with specification of NC toward an autonomic fate requiring vascular endothelial cell (EC-secreted nitric oxide (NO and direct contact with vascular smooth muscle cells (VSMCs via T-cadherin-mediated homotypic interactions. Once a neurovascular template has been established, NT-derived central neurons then align themselves with the vasculature. Our findings reveal that, in early human development, the autonomic nervous system forms in response to distinct molecular cues from VSMCs and ECs, providing a model for how other developing lineages might coordinate their co-patterning.

Neurolinguistics Aspects of Second Language Acquisition

Directory of Open Access Journals (Sweden)

Laleh Fakhraee Faruji

2011-12-01

Full Text Available   Fundamental breakthroughs in the neurosciences, combined with technical innovations for measuring brain activity, are shedding new light on the neural basis of second language (L2
processing, and on its relationship to native language processing (L1 (Perani & Abutalebi, 2005.  Over the past two decades, a large body of neuroimaging studies has been devoted to the study of the neural organization of language (De´monet, Thierry, & Cardebat, 2005; Indefrey & Levelt, 2004; Price, 2000 as cited in Abutalebi, 2008. The value that functional neuroimaging adds to language research is to improve the perspective on the distributed anatomy of language. Thus, it can be used with considerable precision to identify the neural networks underlying the different domains of language processing. In this paper some main issues related to neurolinguistics and second language acquisition with a focus on bilingualism will be discussed.

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 networks, nativism, and the plausibility of constructivism.

Science.gov (United States)

Quartz, S R

1993-09-01

Recent interest in PDP (parallel distributed processing) models is due in part to the widely held belief that they challenge many of the assumptions of classical cognitive science. In the domain of language acquisition, for example, there has been much interest in the claim that PDP models might undermine nativism. Related arguments based on PDP learning have also been given against Fodor's anti-constructivist position--a position that has contributed to the widespread dismissal of constructivism. A limitation of many of the claims regarding PDP learning, however, is that the principles underlying this learning have not been rigorously characterized. In this paper, I examine PDP models from within the framework of Valiant's PAC (probably approximately correct) model of learning, now the dominant model in machine learning, and which applies naturally to neural network learning. From this perspective, I evaluate the implications of PDP models for nativism and Fodor's influential anti-constructivist position. In particular, I demonstrate that, contrary to a number of claims, PDP models are nativist in a robust sense. I also demonstrate that PDP models actually serve as a good illustration of Fodor's anti-constructivist position. While these results may at first suggest that neural network models in general are incapable of the sort of concept acquisition that is required to refute Fodor's anti-constructivist position, I suggest that there is an alternative form of neural network learning that demonstrates the plausibility of constructivism. This alternative form of learning is a natural interpretation of the constructivist position in terms of neural network learning, as it employs learning algorithms that incorporate the addition of structure in addition to weight modification schemes. By demonstrating that there is a natural and plausible interpretation of constructivism in terms of neural network learning, the position that nativism is the only plausible model of

"Fate: The short film"

OpenAIRE

Maya Quintana, Jennifer

2014-01-01

"Fate: The Short Film" is a four minute short film which reflects the idea that nobody can escape from the fate. It has a good picture and sound quality with an understandable message for all public and with the collaboration of actors, filmmaker, stylist, script advisor and media technician.

A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination.

Science.gov (United States)

Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Shi, Yanhong

2009-04-01

MicroRNAs have been implicated as having important roles in stem cell biology. MicroRNA-9 (miR-9) is expressed specifically in neurogenic areas of the brain and may be involved in neural stem cell self-renewal and differentiation. We showed previously that the nuclear receptor TLX is an essential regulator of neural stem cell self-renewal. Here we show that miR-9 suppresses TLX expression to negatively regulate neural stem cell proliferation and accelerate neural differentiation. Introducing a TLX expression vector that is not prone to miR-9 regulation rescued miR-9-induced proliferation deficiency and inhibited precocious differentiation. In utero electroporation of miR-9 in embryonic brains led to premature differentiation and outward migration of the transfected neural stem cells. Moreover, TLX represses expression of the miR-9 pri-miRNA. By forming a negative regulatory loop with TLX, miR-9 provides a model for controlling the balance between neural stem cell proliferation and differentiation.

Activin/Nodal Signaling Supports Retinal Progenitor Specification in a Narrow Time Window during Pluripotent Stem Cell Neuralization

Directory of Open Access Journals (Sweden)

Michele Bertacchi

2015-10-01

Full Text Available Retinal progenitors are initially found in the anterior neural plate region known as the eye field, whereas neighboring areas undertake telencephalic or hypothalamic development. Eye field cells become specified by switching on a network of eye field transcription factors, but the extracellular cues activating this network remain unclear. In this study, we used chemically defined media to induce in vitro differentiation of mouse embryonic stem cells (ESCs toward eye field fates. Inhibition of Wnt/β-catenin signaling was sufficient to drive ESCs to telencephalic, but not retinal, fates. Instead, retinal progenitors could be generated from competent differentiating mouse ESCs by activation of Activin/Nodal signaling within a narrow temporal window corresponding to the emergence of primitive anterior neural progenitors. Activin also promoted eye field gene expression in differentiating human ESCs. Our results reveal insights into the mechanisms of eye field specification and open new avenues toward the generation of retinal progenitors for translational medicine.

Lunatic fringe-mediated Notch signaling regulates adult hippocampal neural stem cell maintenance.

Science.gov (United States)

Semerci, Fatih; Choi, William Tin-Shing; Bajic, Aleksandar; Thakkar, Aarohi; Encinas, Juan Manuel; Depreux, Frederic; Segil, Neil; Groves, Andrew K; Maletic-Savatic, Mirjana

2017-07-12

Hippocampal neural stem cells (NSCs) integrate inputs from multiple sources to balance quiescence and activation. Notch signaling plays a key role during this process. Here, we report that Lunatic fringe ( Lfng), a key modifier of the Notch receptor, is selectively expressed in NSCs. Further, Lfng in NSCs and Notch ligands Delta1 and Jagged1, expressed by their progeny, together influence NSC recruitment, cell cycle duration, and terminal fate. We propose a new model in which Lfng-mediated Notch signaling enables direct communication between a NSC and its descendants, so that progeny can send feedback signals to the 'mother' cell to modify its cell cycle status. Lfng-mediated Notch signaling appears to be a key factor governing NSC quiescence, division, and fate.

Concentration Sensing by the Moving Nucleus in Cell Fate Determination: A Computational Analysis.

Directory of Open Access Journals (Sweden)

Varun Aggarwal

Full Text Available During development of the vertebrate neuroepithelium, the nucleus in neural progenitor cells (NPCs moves from the apex toward the base and returns to the apex (called interkinetic nuclear migration at which point the cell divides. The fate of the resulting daughter cells is thought to depend on the sampling by the moving nucleus of a spatial concentration profile of the cytoplasmic Notch intracellular domain (NICD. However, the nucleus executes complex stochastic motions including random waiting and back and forth motions, which can expose the nucleus to randomly varying levels of cytoplasmic NICD. How nuclear position can determine daughter cell fate despite the stochastic nature of nuclear migration is not clear. Here we derived a mathematical model for reaction, diffusion, and nuclear accumulation of NICD in NPCs during interkinetic nuclear migration (INM. Using experimentally measured trajectory-dependent probabilities of nuclear turning, nuclear waiting times and average nuclear speeds in NPCs in the developing zebrafish retina, we performed stochastic simulations to compute the nuclear trajectory-dependent probabilities of NPC differentiation. Comparison with experimentally measured nuclear NICD concentrations and trajectory-dependent probabilities of differentiation allowed estimation of the NICD cytoplasmic gradient. Spatially polarized production of NICD, rapid NICD cytoplasmic consumption and the time-averaging effect of nuclear import/export kinetics are sufficient to explain the experimentally observed differentiation probabilities. Our computational studies lend quantitative support to the feasibility of the nuclear concentration-sensing mechanism for NPC fate determination in zebrafish retina.

Biophysical characteristics reveal neural stem cell differentiation potential.

Directory of Open Access Journals (Sweden)

Fatima H Labeed

Full Text Available Distinguishing human neural stem/progenitor cell (huNSPC populations that will predominantly generate neurons from those that produce glia is currently hampered by a lack of sufficient cell type-specific surface markers predictive of fate potential. This limits investigation of lineage-biased progenitors and their potential use as therapeutic agents. A live-cell biophysical and label-free measure of fate potential would solve this problem by obviating the need for specific cell surface markers.We used dielectrophoresis (DEP to analyze the biophysical, specifically electrophysiological, properties of cortical human and mouse NSPCs that vary in differentiation potential. Our data demonstrate that the electrophysiological property membrane capacitance inversely correlates with the neurogenic potential of NSPCs. Furthermore, as huNSPCs are continually passaged they decrease neuron generation and increase membrane capacitance, confirming that this parameter dynamically predicts and negatively correlates with neurogenic potential. In contrast, differences in membrane conductance between NSPCs do not consistently correlate with the ability of the cells to generate neurons. DEP crossover frequency, which is a quantitative measure of cell behavior in DEP, directly correlates with neuron generation of NSPCs, indicating a potential mechanism to separate stem cells biased to particular differentiated cell fates.We show here that whole cell membrane capacitance, but not membrane conductance, reflects and predicts the neurogenic potential of human and mouse NSPCs. Stem cell biophysical characteristics therefore provide a completely novel and quantitative measure of stem cell fate potential and a label-free means to identify neuron- or glial-biased progenitors.

Neural network scatter correction technique for digital radiography

International Nuclear Information System (INIS)

Boone, J.M.

1990-01-01

This paper presents a scatter correction technique based on artificial neural networks. The technique utilizes the acquisition of a conventional digital radiographic image, coupled with the acquisition of a multiple pencil beam (micro-aperture) digital image. Image subtraction results in a sparsely sampled estimate of the scatter component in the image. The neural network is trained to develop a causal relationship between image data on the low-pass filtered open field image and the sparsely sampled scatter image, and then the trained network is used to correct the entire image (pixel by pixel) in a manner which is operationally similar to but potentially more powerful than convolution. The technique is described and is illustrated using clinical primary component images combined with scatter component images that are realistically simulated using the results from previously reported Monte Carlo investigations. The results indicate that an accurate scatter correction can be realized using this technique

Neural processing of race during imitation: self-similarity versus social status

Science.gov (United States)

Reynolds Losin, Elizabeth A.; Cross, Katy A.; Iacoboni, Marco; Dapretto, Mirella

2017-01-01

People preferentially imitate others who are similar to them or have high social status. Such imitative biases are thought to have evolved because they increase the efficiency of cultural acquisition. Here we focused on distinguishing between self-similarity and social status as two candidate mechanisms underlying neural responses to a person’s race during imitation. We used fMRI to measure neural responses when 20 African American (AA) and 20 European American (EA) young adults imitated AA, EA and Chinese American (CA) models and also passively observed their gestures and faces. We found that both AA and EA participants exhibited more activity in lateral fronto-parietal and visual regions when imitating AAs compared to EAs or CAs. These results suggest that racial self-similarity is not likely to modulate neural responses to race during imitation, in contrast with findings from previous neuroimaging studies of face perception and action observation. Furthermore, AA and EA participants associated AAs with lower social status than EAs or CAs, suggesting that the social status associated with different racial groups may instead modulate neural activity during imitation of individuals from those groups. Taken together, these findings suggest that neural responses to race during imitation are driven by socially-learned associations rather than self-similarity. This may reflect the adaptive role of imitation in social learning, where learning from higher-status models can be more beneficial. This study provides neural evidence consistent with evolutionary theories of cultural acquisition. PMID:23813738

EEG in the classroom: Synchronised neural recordings during video presentation

DEFF Research Database (Denmark)

Poulsen, Andreas Trier; Kamronn, Simon Due; Dmochowski, Jacek

2017-01-01

We performed simultaneous recordings of electroencephalography (EEG) from multiple students in a classroom, and measured the inter-subject correlation (ISC) of activity evoked by a common video stimulus. The neural reliability, as quantified by ISC, has been linked to engagement and attentional......-evoked neural responses, known to be modulated by attention, can be tracked for groups of students with synchronized EEG acquisition. This is a step towards real-time inference of engagement in the classroom....

Examining neural correlates of skill acquisition in a complex videogame training program

OpenAIRE

Prakash, Ruchika S.; De Leon, Angeline A.; Mourany, Lyla; Lee, Hyunkyu; Voss, Michelle W.; Boot, Walter R.; Basak, Chandramallika; Fabiani, Monica; Gratton, Gabriele; Kramer, Arthur F.

2012-01-01

Acquisition of complex skills is a universal feature of human behavior that has been conceptualized as a process that starts with intense resource dependency, requires effortful cognitive control, and ends in relative automaticity on the multi-faceted task. The present study examined the effects of different theoretically based training strategies on cortical recruitment during acquisition of complex video game skills. Seventy-five participants were recruited and assigned to one of three trai...

Choice of pesticide fate models

International Nuclear Information System (INIS)

Balderacchi, Matteo; Trevisan, Marco; Vischetti, Costantino

2006-01-01

The choice of a pesticide fate model at field scale is linked to the available input data. The article describes the available pesticide fate models at a field scale and the guidelines for the choice of the suitable model as function of the data input requested [it

Stress, glucocorticoid hormones, and hippocampal neural progenitor cells: implications to mood disorders.

Science.gov (United States)

Kino, Tomoshige

2015-01-01

The hypothalamic-pituitary-adrenal (HPA) axis and its end-effectors glucocorticoid hormones play central roles in the adaptive response to numerous stressors that can be either internal or external. Thus, this system has a strong impact on the brain hippocampus and its major functions, such as cognition, memory as well as behavior, and mood. The hippocampal area of the adult brain contains neural stem cells or more committed neural progenitor cells, which retain throughout the human life the ability of self-renewal and to differentiate into multiple neural cell lineages, such as neurons, astrocytes, and oligodendrocytes. Importantly, these characteristic cells contribute significantly to the above-indicated functions of the hippocampus, while various stressors and glucocorticoids influence proliferation, differentiation, and fate of these cells. This review offers an overview of the current understanding on the interactions between the HPA axis/glucocorticoid stress-responsive system and hippocampal neural progenitor cells by focusing on the actions of glucocorticoids. Also addressed is a further discussion on the implications of such interactions to the pathophysiology of mood disorders.

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.

Immunocytochemistry and metamorphic fate of the larval nervous system of Triphyllozoon mucronatum (Ectoprocta: Gymnolaemata: Cheilostomata)

DEFF Research Database (Denmark)

Wanninger, Andreas; Koop, Demian; Degnan, Bernard M.

2005-01-01

The development of gymnolaemate Ectoprocta includes a larval stage of either the coronate or the cyphonautes type. Herein, we provide the first description of the larval neural anatomy of a coronate larva using immunocytochemical methods. We used antibodies against the neurotransmitters serotonin...... that the larval neuroanatomy and the processes that underlie the reorganization of larval organ systems during metamorphosis may vary much more among lophotrochozoan taxa than previously thought....... and FMRFamide and followed the fate of immunoreactive cells through metamorphosis. The larval serotonergic nervous system of Triphyllozoon mucronatum consists of an apical commissure, one pair of lateral axons, a coronate nerve net, an internal nerve mesh, and one pair of axons innervating the frontal organ....... FMRFamide is only found in the larval commissure and in the lateral axons. The entire serotonergic and FMRFamidergic nervous system is lost during metamorphosis and the adult neural structures form independent of the larval ones. In the postlarval zooid, both neurotransmitters are detected in the cerebral...

A multimedia fate model to evaluate the fate of PAHs in Songhua River, China

International Nuclear Information System (INIS)

Wang Ce; Feng Yujie; Sun Qingfang; Zhao Shanshan; Gao Peng; Li Bailian

2012-01-01

A multimedia fate model coupling dynamic water flow with a level IV fugacity model has been developed and applied to simulate the temporal and spatial fate of Polycyclic Aromatic Hydrocarbons (PAHs) in the Songhua River, China. The model has two components: in the first, the one-dimensional network kinematic wave equation is used to calculate varying water flow and depth. In the second, Fugacity IV equations are implemented to predict contaminant distributions in four environmental media. The estimated concentrations of eight PAHs in Songhua River are obtained, and all simulated results are in acceptable agreement with monitoring data, as verified with the Theil’s inequality coefficient test. The sensitivity of PAH concentration in each environmental phase to input parameters are also evaluated. Our results show the model predicts reasonably accurate contaminant concentrations in natural rivers, and that it can be used to supply necessary information for control and management of water pollution. - Highlights: ► The model used was developed based on kinematic wave equation and level IV fugacity principle. ► The model was applied to describe the fate and transport of organic chemicals in natural river. ► The concentrations of PAHs in water column were satisfactorily simulated when compared with monitoring data. ► Temporal and spatial variability of PAHs concentration among multimedia environmental phases was illustrated. - A dynamic water flow based multimedia fate model is developed to characterize the fate and transport of organic contaminant in natural rivers.

Non-Viral Generation of Neural Precursor-like Cells from Adult Human Fibroblasts

Directory of Open Access Journals (Sweden)

Maucksch C

2012-01-01

Full Text Available Recent studies have reported direct reprogramming of human fibroblasts to mature neurons by the introduction of defined neural genes. This technology has potential use in the areas of neurological disease modeling and drug development. However, use of induced neurons for large-scale drug screening and cell-based replacement strategies is limited due to their inability to expand once reprogrammed. We propose it would be more desirable to induce expandable neural precursor cells directly from human fibroblasts. To date several pluripotent and neural transcription factors have been shown to be capable of converting mouse fibroblasts to neural stem/precursor-like cells when delivered by viral vectors. Here we extend these findings and demonstrate that transient ectopic insertion of the transcription factors SOX2 and PAX6 to adult human fibroblasts through use of non-viral plasmid transfection or protein transduction allows the generation of induced neural precursor (iNP colonies expressing a range of neural stem and pro-neural genes. Upon differentiation, iNP cells give rise to neurons exhibiting typical neuronal morphologies and expressing multiple neuronal markers including tyrosine hydroxylase and GAD65/67. Importantly, iNP-derived neurons demonstrate electrophysiological properties of functionally mature neurons with the capacity to generate action potentials. In addition, iNP cells are capable of differentiating into glial fibrillary acidic protein (GFAP-expressing astrocytes. This study represents a novel virus-free approach for direct reprogramming of human fibroblasts to a neural precursor fate.

Single-Cell Transcriptomics and Fate Mapping of Ependymal Cells Reveals an Absence of Neural Stem Cell Function.

Science.gov (United States)

Shah, Prajay T; Stratton, Jo A; Stykel, Morgan Gail; Abbasi, Sepideh; Sharma, Sandeep; Mayr, Kyle A; Koblinger, Kathrin; Whelan, Patrick J; Biernaskie, Jeff

2018-05-03

Ependymal cells are multi-ciliated cells that form the brain's ventricular epithelium and a niche for neural stem cells (NSCs) in the ventricular-subventricular zone (V-SVZ). In addition, ependymal cells are suggested to be latent NSCs with a capacity to acquire neurogenic function. This remains highly controversial due to a lack of prospective in vivo labeling techniques that can effectively distinguish ependymal cells from neighboring V-SVZ NSCs. We describe a transgenic system that allows for targeted labeling of ependymal cells within the V-SVZ. Single-cell RNA-seq revealed that ependymal cells are enriched for cilia-related genes and share several stem-cell-associated genes with neural stem or progenitors. Under in vivo and in vitro neural-stem- or progenitor-stimulating environments, ependymal cells failed to demonstrate any suggestion of latent neural-stem-cell function. These findings suggest remarkable stability of ependymal cell function and provide fundamental insights into the molecular signature of the V-SVZ niche. Copyright © 2018 Elsevier Inc. All rights reserved.

Estimating the Acquisition Price of Enshi Yulu Young Tea Shoots Using Near-Infrared Spectroscopy by the Back Propagation Artificial Neural Network Model in Conjunction with Backward Interval Partial Least Squares Algorithm

Science.gov (United States)

Wang, Sh.-P.; Gong, Z.-M.; Su, X.-Zh.; Liao, J.-Zh.

2017-09-01

Near infrared spectroscopy and the back propagation artificial neural network model in conjunction with backward interval partial least squares algorithm were used to estimate the purchasing price of Enshi yulu young tea shoots. The near-infrared spectra regions most relevant to the tea shoots price model (5700.5-5935.8, 7613.6-7848.9, 8091.8-8327.1, 8331-8566.2, 9287.5-9522.5, and 9526.6-9761.9 cm-1) were selected using backward interval partial least squares algorithm. The first five principal components that explained 99.96% of the variability in those selected spectral data were then used to calibrate the back propagation artificial neural tea shoots purchasing price model. The performance of this model (coefficient of determination for prediction 0.9724; root-mean-square error of prediction 4.727) was superior to those of the back propagation artificial neural model (coefficient of determination for prediction 0.8653, root-mean-square error of prediction 5.125) and the backward interval partial least squares model (coefficient of determination for prediction 0.5932, root-mean-square error of prediction 25.125). The acquisition price model with the combined backward interval partial least squares-back propagation artificial neural network algorithms can evaluate the price of Enshi yulu tea shoots accurately, quickly and objectively.

miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells.

Science.gov (United States)

Sun, GuoQiang; Ye, Peng; Murai, Kiyohito; Lang, Ming-Fei; Li, Shengxiu; Zhang, Heying; Li, Wendong; Fu, Chelsea; Yin, Jason; Wang, Allen; Ma, Xiaoxiao; Shi, Yanhong

2011-11-08

miR-137 is a brain-enriched microRNA. Its role in neural development remains unknown. Here we show that miR-137 has an essential role in controlling embryonic neural stem cell fate determination. miR-137 negatively regulates cell proliferation and accelerates neural differentiation of embryonic neural stem cells. In addition, we show that the histone lysine-specific demethylase 1 (LSD1), a transcriptional co-repressor of nuclear receptor TLX, is a downstream target of miR-137. In utero electroporation of miR-137 in embryonic mouse brains led to premature differentiation and outward migration of the transfected cells. Introducing a LSD1 expression vector lacking the miR-137 recognition site rescued miR-137-induced precocious differentiation. Furthermore, we demonstrate that TLX, an essential regulator of neural stem cell self-renewal, represses the expression of miR-137 by recruiting LSD1 to the genomic regions of miR-137. Thus, miR-137 forms a feedback regulatory loop with TLX and LSD1 to control the dynamics between neural stem cell proliferation and differentiation during neural development.

A Constructive Neural-Network Approach to Modeling Psychological Development

Science.gov (United States)

Shultz, Thomas R.

2012-01-01

This article reviews a particular computational modeling approach to the study of psychological development--that of constructive neural networks. This approach is applied to a variety of developmental domains and issues, including Piagetian tasks, shift learning, language acquisition, number comparison, habituation of visual attention, concept…

Putative oncogene Brachyury (T) is essential to specify cell fate but dispensable for notochord progenitor proliferation and EMT.

Science.gov (United States)

Zhu, Jianjian; Kwan, Kin Ming; Mackem, Susan

2016-04-05

The transcription factor Brachyury (T) gene is expressed throughout primary mesoderm (primitive streak and notochord) during early embryonic development and has been strongly implicated in the genesis of chordoma, a sarcoma of notochord cell origin. Additionally, T expression has been found in and proposed to play a role in promoting epithelial-mesenchymal transition (EMT) in various other types of human tumors. However, the role of T in normal mammalian notochord development and function is still not well-understood. We have generated an inducible knockdown model to efficiently and selectively deplete T from notochord in mouse embryos. In combination with genetic lineage tracing, we show that T function is essential for maintaining notochord cell fate and function. Progenitors adopt predominantly a neural fate in the absence of T, consistent with an origin from a common chordoneural progenitor. However, T function is dispensable for progenitor cell survival, proliferation, and EMT, which has implications for the therapeutic targeting of T in chordoma and other cancers.

A longitudinal study investigating neural processing of speech envelope modulation rates in children with (a family risk for) dyslexia.

Science.gov (United States)

De Vos, Astrid; Vanvooren, Sophie; Vanderauwera, Jolijn; Ghesquière, Pol; Wouters, Jan

2017-08-01

Recent evidence suggests that a fundamental deficit in the synchronization of neural oscillations to temporal information in speech may underlie phonological processing problems in dyslexia. Since previous studies were performed cross-sectionally in school-aged children or adults, developmental aspects of neural auditory processing in relation to reading acquisition and dyslexia remain to be investigated. The present longitudinal study followed 68 children during development from pre-reader (5 years old) to beginning reader (7 years old) and more advanced reader (9 years old). Thirty-six children had a family risk for dyslexia and 14 children eventually developed dyslexia. EEG recordings of auditory steady-state responses to 4 and 20 Hz modulations, corresponding to syllable and phoneme rates, were collected at each point in time. Our results demonstrate an increase in neural synchronization to phoneme-rate modulations around the onset of reading acquisition. This effect was negatively correlated with later reading and phonological skills, indicating that children who exhibit the largest increase in neural synchronization to phoneme rates, develop the poorest reading and phonological skills. Accordingly, neural synchronization to phoneme-rate modulations was found to be significantly higher in beginning and more advanced readers with dyslexia. We found no developmental effects regarding neural synchronization to syllable rates, nor any effects of a family risk for dyslexia. Altogether, our findings suggest that the onset of reading instruction coincides with an increase in neural responsiveness to phoneme-rate modulations, and that the extent of this increase is related to (the outcome of) reading development. Hereby, dyslexic children persistently demonstrate atypically high neural synchronization to phoneme rates from the beginning of reading acquisition onwards. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adipose stromal cells contain phenotypically distinct adipogenic progenitors derived from neural crest.

Directory of Open Access Journals (Sweden)

Yoshihiro Sowa

Full Text Available Recent studies have shown that adipose-derived stromal/stem cells (ASCs contain phenotypically and functionally heterogeneous subpopulations of cells, but their developmental origin and their relative differentiation potential remain elusive. In the present study, we aimed at investigating how and to what extent the neural crest contributes to ASCs using Cre-loxP-mediated fate mapping. ASCs harvested from subcutaneous fat depots of either adult P0-Cre/or Wnt1-Cre/Floxed-reporter mice contained a few neural crest-derived ASCs (NCDASCs. This subpopulation of cells was successfully expanded in vitro under standard culture conditions and their growth rate was comparable to non-neural crest derivatives. Although NCDASCs were positive for several mesenchymal stem cell markers as non-neural crest derivatives, they exhibited a unique bipolar or multipolar morphology with higher expression of markers for both neural crest progenitors (p75NTR, Nestin, and Sox2 and preadipocytes (CD24, CD34, S100, Pref-1, GATA2, and C/EBP-delta. NCDASCs were able to differentiate into adipocytes with high efficiency but their osteogenic and chondrogenic potential was markedly attenuated, indicating their commitment to adipogenesis. In vivo, a very small proportion of adipocytes were originated from the neural crest. In addition, p75NTR-positive neural crest-derived cells were identified along the vessels within the subcutaneous adipose tissue, but they were negative for mural and endothelial markers. These results demonstrate that ASCs contain neural crest-derived adipocyte-restricted progenitors whose phenotype is distinct from that of non-neural crest derivatives.

Neuronal Subtype Generation During Postnatal Olfactory Bulb Neurogenesis.

Science.gov (United States)

Angelova, Alexandra; Tiveron, Marie-Catherine; Cremer, Harold; Beclin, Christophe

2018-01-01

In the perinatal and adult forebrain, regionalized neural stem cells lining the ventricular walls produce different types of olfactory bulb interneurons. Although these postnatal stem cells are lineage related to their embryonic counterparts that produce, for example, cortical, septal, and striatal neurons, their output at the level of neuronal phenotype changes dramatically. Tiveron et al. investigated the molecular determinants underlying stem cell regionalization and the gene expression changes inducing the shift from embryonic to adult neuron production. High-resolution gene expression analyses of different lineages revealed that the zinc finger proteins, Zic1 and Zic2, are postnatally induced in the dorsal olfactory bulb neuron lineage. Functional studies demonstrated that these factors confer a GABAergic and calretinin-positive phenotype to neural stem cells while repressing dopaminergic fate. Based on these findings, we discuss the molecular mechanisms that allow acquisition of new traits during the transition from embryonic to adult neurogenesis. We focus on the involvement of epigenetic marks and emphasize why the identification of master transcription factors, that instruct the fate of postnatally generated neurons, can help in deciphering the mechanisms driving fate transition from embryonic to adult neuron production.

Neuronal Subtype Generation During Postnatal Olfactory Bulb Neurogenesis

Directory of Open Access Journals (Sweden)

Alexandra Angelova

2018-02-01

Full Text Available In the perinatal and adult forebrain, regionalized neural stem cells lining the ventricular walls produce different types of olfactory bulb interneurons. Although these postnatal stem cells are lineage related to their embryonic counterparts that produce, for example, cortical, septal, and striatal neurons, their output at the level of neuronal phenotype changes dramatically. Tiveron et al. investigated the molecular determinants underlying stem cell regionalization and the gene expression changes inducing the shift from embryonic to adult neuron production. High-resolution gene expression analyses of different lineages revealed that the zinc finger proteins, Zic1 and Zic2, are postnatally induced in the dorsal olfactory bulb neuron lineage. Functional studies demonstrated that these factors confer a GABAergic and calretinin-positive phenotype to neural stem cells while repressing dopaminergic fate. Based on these findings, we discuss the molecular mechanisms that allow acquisition of new traits during the transition from embryonic to adult neurogenesis. We focus on the involvement of epigenetic marks and emphasize why the identification of master transcription factors, that instruct the fate of postnatally generated neurons, can help in deciphering the mechanisms driving fate transition from embryonic to adult neuron production.

The C. elegans embryonic fate specification factor EGL-18 (GATA) is reutilized downstream of Wnt signaling to maintain a population of larval progenitor cells.

Science.gov (United States)

Gorrepati, Lakshmi; Eisenmann, David M

2015-01-01

In metazoans, stem cells in developing and adult tissues can divide asymmetrically to give rise to a daughter that differentiates and a daughter that retains the progenitor fate. Although the short-lived nematode C. elegans does not possess adult somatic stem cells, the lateral hypodermal seam cells behave in a similar manner: they divide once per larval stage to generate an anterior daughter that adopts a non-dividing differentiated fate and a posterior daughter that retains the seam fate and the ability to divide further. Wnt signaling pathway is known to regulate the asymmetry of these divisions and maintain the progenitor cell fate in one daughter, but how activation of the Wnt pathway accomplished this was unknown. We describe here our recent work that identified the GATA transcription factor EGL-18 as a downstream target of Wnt signaling necessary for maintenance of a progenitor population of larval seam cells. EGL-18 was previously shown to act in the initial specification of the seam cells in the embryo. Thus the acquisition of a Wnt-responsive cis-regulatory module allows an embryonic fate specification factor to be reutilized later in life downstream of a different regulator (Wnt signaling) to maintain a progenitor cell population. These results support the use of seam cell development in C. elegans as a simple model system for studying stem and progenitor cell biology.

The neural fate of neutral information in emotion-enhanced memory.

Science.gov (United States)

Watts, Sarah; Buratto, Luciano G; Brotherhood, Emilie V; Barnacle, Gemma E; Schaefer, Alexandre

2014-07-01

In this study, we report evidence that neural activity reflecting the encoding of emotionally neutral information in memory is reduced when neutral and emotional stimuli are intermixed during encoding. Specifically, participants studied emotional and neutral pictures organized in mixed lists (in which emotional and neutral pictures were intermixed) or in pure lists (only-neutral or only-emotional pictures) and performed a recall test. To estimate encoding efficiency, we used the Dm effect, measured with event-related potentials. Recall for neutral items was lower in mixed compared to pure lists and posterior Dm activity for neutral items was reduced in mixed lists, whereas it remained robust in pure lists. These findings might be caused by an asymmetrical competition for attentional and working memory resources between emotional and neutral information, which could be a major determinant of emotional memory effects. Copyright © 2014 Society for Psychophysiological Research.

Prospero-related homeobox 1 (Prox1 at the crossroads of diverse pathways during adult neural fate specification

Directory of Open Access Journals (Sweden)

Athanasios eStergiopoulos

2015-01-01

Full Text Available Over the last decades, adult neurogenesis in the central nervous system (CNS has emerged as a fundamental process underlying physiology and disease. Recent evidence indicates that the homeobox transcription factor Prox1 is a critical intrinsic regulator of neurogenesis in the embryonic CNS and adult dentate gyrus (DG of the hippocampus, acting in multiple ways and instructed by extrinsic cues and intrinsic factors. In the embryonic CNS, Prox1 is mechanistically involved in the regulation of proliferation versus differentiation decisions of NSCs, promoting cell cycle exit and neuronal differentiation, while inhibits astrogliogenesis. During the complex differentiation events in adult hippocampal neurogenesis, Prox1 is required for maintenance of intermediate progenitors (IPs, differentiation and maturation of glutamatergic interneurons, as well as specification of DG cell identity over CA3 pyramidal fate. The mechanism by which Prox1 exerts multiple functions involves distinct signaling pathways currently not fully highlighted. In this mini-review, we thoroughly discuss the Prox1-dependent phenotypes and molecular pathways in adult neurogenesis in relation to different upstream signaling cues and cell fate determinants. In addition, we discuss the possibility that Prox1 may act as a cross-talk point between diverse signaling cascades to achieve specific outcomes during adult neurogenesis.

The H3K27 Demethylase JMJD3 Is Required for Maintenance of the Embryonic Respiratory Neuronal Network, Neonatal Breathing, and Survival

Directory of Open Access Journals (Sweden)

Thomas Burgold

2012-11-01

Full Text Available JMJD3 (KDM6B antagonizes Polycomb silencing by demethylating lysine 27 on histone H3. The interplay of methyltransferases and demethylases at this residue is thought to underlie critical cell fate transitions, and the dynamics of H3K27me3 during neurogenesis posited for JMJD3 a critical role in the acquisition of neural fate. Despite evidence of its involvement in early neural commitment, however, its role in the emergence and maturation of the mammalian CNS remains unknown. Here, we inactivated Jmjd3 in the mouse and found that its loss causes perinatal lethality with the complete and selective disruption of the pre-Bötzinger complex (PBC, the pacemaker of the respiratory rhythm generator. Through genetic and electrophysiological approaches, we show that the enzymatic activity of JMJD3 is selectively required for the maintenance of the PBC and controls critical regulators of PBC activity, uncovering an unanticipated role of this enzyme in the late structuring and function of neuronal networks.

Roles of bHLH genes in neural stem cell differentiation

International Nuclear Information System (INIS)

Kageyama, Ryoichiro; Ohtsuka, Toshiyuki; Hatakeyama, Jun; Ohsawa, Ryosuke

2005-01-01

Neural stem cells change their characteristics over time during development: they initially proliferate only and then give rise to neurons first and glial cells later. In the absence of the repressor-type basic helix-loop-helix (bHLH) genes Hes1, Hes3 and Hes5, neural stem cells do not proliferate sufficiently but prematurely differentiate into neurons and become depleted without making the later born cell types such as astrocytes and ependymal cells. Thus, Hes genes are essential for maintenance of neural stem cells to make cells not only in correct numbers but also in full diversity. Hes genes antagonize the activator-type bHLH genes, which include Mash1, Math and Neurogenin. The activator-type bHLH genes promote the neuronal fate determination and induce expression of Notch ligands such as Delta. These ligands activate Notch signaling and upregulate Hes1 and Hes5 expression in neighboring cells, thereby maintaining these cells undifferentiated. Thus, the activator-type and repressor-type bHLH genes regulate each other, allowing only subsets of cells to undergo differentiation while keeping others to stay neural stem cells. This regulation is essential for generation of complex brain structures of appropriate size, shape and cell arrangement

The aged brain: genesis and fate of residual progenitor cells in the subventricular zone

Directory of Open Access Journals (Sweden)

Vivian eCapilla-Gonzalez

2015-09-01

Full Text Available Neural stem cells persist in the adult mammalian brain through life. The subventricular zone is the largest source of stem cells in the nervous system, and continuously generates new neuronal and glial cells involved in brain regeneration. During aging, the germinal potential of the subventricular zone suffers a widespread decline, but the causes of this turn down are not fully understood. This review provides a compilation of the current knowledge about the age-related changes in the neural stem cell population, as well as the fate of the newly generated cells in the aged brain. It is known that the neurogenic capacity is clearly disrupted during aging, while the production of oligodendroglial cells is not compromised. Interestingly, the human brain seems to primarily preserve the ability to produce new oligodendrocytes instead of neurons, which could be related to the development of neurological disorders. Further studies in this matter are required to improve our understanding and the current strategies for fighting neurological diseases associated with senescence.

Differentiation of neurons from neural precursors generated in floating spheres from embryonic stem cells

Directory of Open Access Journals (Sweden)

Forrester Jeff

2009-09-01

Full Text Available Abstract Background Neural differentiation of embryonic stem (ES cells is usually achieved by induction of ectoderm in embryoid bodies followed by the enrichment of neuronal progenitors using a variety of factors. Obtaining reproducible percentages of neural cells is difficult and the methods are time consuming. Results Neural progenitors were produced from murine ES cells by a combination of nonadherent conditions and serum starvation. Conversion to neural progenitors was accompanied by downregulation of Oct4 and NANOG and increased expression of nestin. ES cells containing a GFP gene under the control of the Sox1 regulatory regions became fluorescent upon differentiation to neural progenitors, and ES cells with a tau-GFP fusion protein became fluorescent upon further differentiation to neurons. Neurons produced from these cells upregulated mature neuronal markers, or differentiated to glial and oligodendrocyte fates. The neurons gave rise to action potentials that could be recorded after application of fixed currents. Conclusion Neural progenitors were produced from murine ES cells by a novel method that induced neuroectoderm cells by a combination of nonadherent conditions and serum starvation, in contrast to the embryoid body method in which neuroectoderm cells must be selected after formation of all three germ layers.

Shaping the learning curve: epigenetic dynamics in neural plasticity

Directory of Open Access Journals (Sweden)

Zohar Ziv Bronfman

2014-07-01

Full Text Available A key characteristic of learning and neural plasticity is state-dependent acquisition dynamics reflected by the non-linear learning curve that links increase in learning with practice. Here we propose that the manner by which epigenetic states of individual cells change during learning contributes to the shape of the neural and behavioral learning curve. We base our suggestion on recent studies showing that epigenetic mechanisms such as DNA methylation, histone acetylation and RNA-mediated gene regulation are intimately involved in the establishment and maintenance of long-term neural plasticity, reflecting specific learning-histories and influencing future learning. Our model, which is the first to suggest a dynamic molecular account of the shape of the learning curve, leads to several testable predictions regarding the link between epigenetic dynamics at the promoter, gene-network and neural-network levels. This perspective opens up new avenues for therapeutic interventions in neurological pathologies.

Chemically Induced Reprogramming of Somatic Cells to Pluripotent Stem Cells and Neural Cells.

Science.gov (United States)

Biswas, Dhruba; Jiang, Peng

2016-02-06

The ability to generate transplantable neural cells in a large quantity in the laboratory is a critical step in the field of developing stem cell regenerative medicine for neural repair. During the last few years, groundbreaking studies have shown that cell fate of adult somatic cells can be reprogrammed through lineage specific expression of transcription factors (TFs)-and defined culture conditions. This key concept has been used to identify a number of potent small molecules that could enhance the efficiency of reprogramming with TFs. Recently, a growing number of studies have shown that small molecules targeting specific epigenetic and signaling pathways can replace all of the reprogramming TFs. Here, we provide a detailed review of the studies reporting the generation of chemically induced pluripotent stem cells (ciPSCs), neural stem cells (ciNSCs), and neurons (ciN). We also discuss the main mechanisms of actions and the pathways that the small molecules regulate during chemical reprogramming.

Neural Progenitors Adopt Specific Identities by Directly Repressing All Alternative Progenitor Transcriptional Programs.

Science.gov (United States)

Kutejova, Eva; Sasai, Noriaki; Shah, Ankita; Gouti, Mina; Briscoe, James

2016-03-21

In the vertebrate neural tube, a morphogen-induced transcriptional network produces multiple molecularly distinct progenitor domains, each generating different neuronal subtypes. Using an in vitro differentiation system, we defined gene expression signatures of distinct progenitor populations and identified direct gene-regulatory inputs corresponding to locations of specific transcription factor binding. Combined with targeted perturbations of the network, this revealed a mechanism in which a progenitor identity is installed by active repression of the entire transcriptional programs of other neural progenitor fates. In the ventral neural tube, sonic hedgehog (Shh) signaling, together with broadly expressed transcriptional activators, concurrently activates the gene expression programs of several domains. The specific outcome is selected by repressive input provided by Shh-induced transcription factors that act as the key nodes in the network, enabling progenitors to adopt a single definitive identity from several initially permitted options. Together, the data suggest design principles relevant to many developing tissues. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Due Diligence Processes for Public Acquisition of Mining-Impacted Landscapes

Science.gov (United States)

Martin, E.; Monohan, C.; Keeble-Toll, A. K.

2016-12-01

The acquisition of public land is critical for achieving conservation and habitat goals in rural regions projected to experience continuously high rates of population growth. To ensure that public funds are utilized responsibly in the purchase of conservation easements appropriate due diligence processes must be established that limit landowner liability post-acquisition. Traditional methods of characterizing contamination in regions where legacy mining activities were prevalent may not utilize current scientific knowledge and understanding of contaminant fate, transport and bioavailability, and therefore are likely to have type two error. Agency prescribed assessment methods utilized under CERLA in many cases fail to detect contamination that presents liability issues by failing to require water quality sampling that would reveal offsite transport potential of contaminants posing human health risks, including mercury. Historical analysis can be used to inform judgmental sampling to identify hotspots and contaminants of concern. Land acquisition projects at two historic mine sites in Nevada County, California, the Champion Mine Complex and the Black Swan Preserve have established the necessity of re-thinking due diligence processes for mining-impacted landscapes. These pilot projects demonstrate that pre-acquisition assessment in the Gold Country must include judgmental sampling and evaluation of contaminant transport. Best practices using the current scientific knowledge must be codified by agencies, consultants, and NGOs in order to ensure responsible use of public funds and to safeguard public health.

Notch signaling patterns neurogenic ectoderm and regulates the asymmetric division of neural progenitors in sea urchin embryos.

Science.gov (United States)

Mellott, Dan O; Thisdelle, Jordan; Burke, Robert D

2017-10-01

We have examined regulation of neurogenesis by Delta/Notch signaling in sea urchin embryos. At gastrulation, neural progenitors enter S phase coincident with expression of Sp-SoxC. We used a BAC containing GFP knocked into the Sp-SoxC locus to label neural progenitors. Live imaging and immunolocalizations indicate that Sp-SoxC-expressing cells divide to produce pairs of adjacent cells expressing GFP. Over an interval of about 6 h, one cell fragments, undergoes apoptosis and expresses high levels of activated Caspase3. A Notch reporter indicates that Notch signaling is activated in cells adjacent to cells expressing Sp-SoxC. Inhibition of γ-secretase, injection of Sp-Delta morpholinos or CRISPR/Cas9-induced mutation of Sp-Delta results in supernumerary neural progenitors and neurons. Interfering with Notch signaling increases neural progenitor recruitment and pairs of neural progenitors. Thus, Notch signaling restricts the number of neural progenitors recruited and regulates the fate of progeny of the asymmetric division. We propose a model in which localized signaling converts ectodermal and ciliary band cells to neural progenitors that divide asymmetrically to produce a neural precursor and an apoptotic cell. © 2017. Published by The Company of Biologists Ltd.

Environmental fate and behaviour of nanomaterials

DEFF Research Database (Denmark)

Hartmann, Nanna Isabella Bloch; Skjolding, Lars Michael; Hansen, Steffen Foss

In the current report, the existing knowledge on the fate of nanomaterials in the environment is reviewed and the major knowledge gaps are identified.......In the current report, the existing knowledge on the fate of nanomaterials in the environment is reviewed and the major knowledge gaps are identified....

Sox5 Functions as a Fate Switch in Medaka Pigment Cell Development

Science.gov (United States)

Nagao, Yusuke; Suzuki, Takao; Shimizu, Atsushi; Kimura, Tetsuaki; Seki, Ryoko; Adachi, Tomoko; Inoue, Chikako; Omae, Yoshihiro; Kamei, Yasuhiro; Hara, Ikuyo; Taniguchi, Yoshihito; Naruse, Kiyoshi; Wakamatsu, Yuko; Kelsh, Robert N.; Hibi, Masahiko; Hashimoto, Hisashi

2014-01-01

Mechanisms generating diverse cell types from multipotent progenitors are crucial for normal development. Neural crest cells (NCCs) are multipotent stem cells that give rise to numerous cell-types, including pigment cells. Medaka has four types of NCC-derived pigment cells (xanthophores, leucophores, melanophores and iridophores), making medaka pigment cell development an excellent model for studying the mechanisms controlling specification of distinct cell types from a multipotent progenitor. Medaka many leucophores-3 (ml-3) mutant embryos exhibit a unique phenotype characterized by excessive formation of leucophores and absence of xanthophores. We show that ml-3 encodes sox5, which is expressed in premigratory NCCs and differentiating xanthophores. Cell transplantation studies reveal a cell-autonomous role of sox5 in the xanthophore lineage. pax7a is expressed in NCCs and required for both xanthophore and leucophore lineages; we demonstrate that Sox5 functions downstream of Pax7a. We propose a model in which multipotent NCCs first give rise to pax7a-positive partially fate-restricted intermediate progenitors for xanthophores and leucophores; some of these progenitors then express sox5, and as a result of Sox5 action develop into xanthophores. Our results provide the first demonstration that Sox5 can function as a molecular switch driving specification of a specific cell-fate (xanthophore) from a partially-restricted, but still multipotent, progenitor (the shared xanthophore-leucophore progenitor). PMID:24699463

Sox5 functions as a fate switch in medaka pigment cell development.

Directory of Open Access Journals (Sweden)

Yusuke Nagao

2014-04-01

Full Text Available Mechanisms generating diverse cell types from multipotent progenitors are crucial for normal development. Neural crest cells (NCCs are multipotent stem cells that give rise to numerous cell-types, including pigment cells. Medaka has four types of NCC-derived pigment cells (xanthophores, leucophores, melanophores and iridophores, making medaka pigment cell development an excellent model for studying the mechanisms controlling specification of distinct cell types from a multipotent progenitor. Medaka many leucophores-3 (ml-3 mutant embryos exhibit a unique phenotype characterized by excessive formation of leucophores and absence of xanthophores. We show that ml-3 encodes sox5, which is expressed in premigratory NCCs and differentiating xanthophores. Cell transplantation studies reveal a cell-autonomous role of sox5 in the xanthophore lineage. pax7a is expressed in NCCs and required for both xanthophore and leucophore lineages; we demonstrate that Sox5 functions downstream of Pax7a. We propose a model in which multipotent NCCs first give rise to pax7a-positive partially fate-restricted intermediate progenitors for xanthophores and leucophores; some of these progenitors then express sox5, and as a result of Sox5 action develop into xanthophores. Our results provide the first demonstration that Sox5 can function as a molecular switch driving specification of a specific cell-fate (xanthophore from a partially-restricted, but still multipotent, progenitor (the shared xanthophore-leucophore progenitor.

Race modulates neural activity during imitation

Science.gov (United States)

Losin, Elizabeth A. Reynolds; Iacoboni, Marco; Martin, Alia; Cross, Katy A.; Dapretto, Mirella

2014-01-01

Imitation plays a central role in the acquisition of culture. People preferentially imitate others who are self-similar, prestigious or successful. Because race can indicate a person's self-similarity or status, race influences whom people imitate. Prior studies of the neural underpinnings of imitation have not considered the effects of race. Here we measured neural activity with fMRI while European American participants imitated meaningless gestures performed by actors of their own race, and two racial outgroups, African American, and Chinese American. Participants also passively observed the actions of these actors and their portraits. Frontal, parietal and occipital areas were differentially activated while participants imitated actors of different races. More activity was present when imitating African Americans than the other racial groups, perhaps reflecting participants' reported lack of experience with and negative attitudes towards this group, or the group's lower perceived social status. This pattern of neural activity was not found when participants passively observed the gestures of the actors or simply looked at their faces. Instead, during face-viewing neural responses were overall greater for own-race individuals, consistent with prior race perception studies not involving imitation. Our findings represent a first step in elucidating neural mechanisms involved in cultural learning, a process that influences almost every aspect of our lives but has thus far received little neuroscientific study. PMID:22062193

Neural mechanisms of song memory formation in juvenile zebra finches

NARCIS (Netherlands)

Moorman, S.

2015-01-01

There are many parallels between the acquisition of spoken language in human infants and song learning in songbirds, at the behavioural, neural, genetic and cognitive levels. Both human infants and juvenile songbirds are able to imitate sounds from adults of the same species (often their parents),

Pulsed DC Electric Field-Induced Differentiation of Cortical Neural Precursor Cells.

Directory of Open Access Journals (Sweden)

Hui-Fang Chang

Full Text Available We report the differentiation of neural stem and progenitor cells solely induced by direct current (DC pulses stimulation. Neural stem and progenitor cells in the adult mammalian brain are promising candidates for the development of therapeutic neuroregeneration strategies. The differentiation of neural stem and progenitor cells depends on various in vivo environmental factors, such as nerve growth factor and endogenous EF. In this study, we demonstrated that the morphologic and phenotypic changes of mouse neural stem and progenitor cells (mNPCs could be induced solely by exposure to square-wave DC pulses (magnitude 300 mV/mm at frequency of 100-Hz. The DC pulse stimulation was conducted for 48 h, and the morphologic changes of mNPCs were monitored continuously. The length of primary processes and the amount of branching significantly increased after stimulation by DC pulses for 48 h. After DC pulse treatment, the mNPCs differentiated into neurons, astrocytes, and oligodendrocytes simultaneously in stem cell maintenance medium. Our results suggest that simple DC pulse treatment could control the fate of NPCs. With further studies, DC pulses may be applied to manipulate NPC differentiation and may be used for the development of therapeutic strategies that employ NPCs to treat nervous system disorders.

Pulsed DC Electric Field-Induced Differentiation of Cortical Neural Precursor Cells.

Science.gov (United States)

Chang, Hui-Fang; Lee, Ying-Shan; Tang, Tang K; Cheng, Ji-Yen

2016-01-01

We report the differentiation of neural stem and progenitor cells solely induced by direct current (DC) pulses stimulation. Neural stem and progenitor cells in the adult mammalian brain are promising candidates for the development of therapeutic neuroregeneration strategies. The differentiation of neural stem and progenitor cells depends on various in vivo environmental factors, such as nerve growth factor and endogenous EF. In this study, we demonstrated that the morphologic and phenotypic changes of mouse neural stem and progenitor cells (mNPCs) could be induced solely by exposure to square-wave DC pulses (magnitude 300 mV/mm at frequency of 100-Hz). The DC pulse stimulation was conducted for 48 h, and the morphologic changes of mNPCs were monitored continuously. The length of primary processes and the amount of branching significantly increased after stimulation by DC pulses for 48 h. After DC pulse treatment, the mNPCs differentiated into neurons, astrocytes, and oligodendrocytes simultaneously in stem cell maintenance medium. Our results suggest that simple DC pulse treatment could control the fate of NPCs. With further studies, DC pulses may be applied to manipulate NPC differentiation and may be used for the development of therapeutic strategies that employ NPCs to treat nervous system disorders.

Neural network based photovoltaic electrical forecasting in south Algeria

International Nuclear Information System (INIS)

Hamid Oudjana, S.; Hellal, A.; Hadj Mahammed, I

2014-01-01

Photovoltaic electrical forecasting is significance for the optimal operation and power predication of grid-connected photovoltaic (PV) plants, and it is important task in renewable energy electrical system planning and operating. This paper explores the application of neural networks (NN) to study the design of photovoltaic electrical forecasting systems for one week ahead using weather databases include the global irradiance, and temperature of Ghardaia city (south of Algeria) for one year of 2013 using a data acquisition system. Simulations were run and the results are discussed showing that neural networks Technique is capable to decrease the photovoltaic electrical forecasting error. (author)

Histone Methylation and microRNA-dependent Regulation of Epigenetic Activities in Neural Progenitor Self-Renewal and Differentiation.

Science.gov (United States)

Cacci, Emanuele; Negri, Rodolfo; Biagioni, Stefano; Lupo, Giuseppe

2017-01-01

Neural stem/progenitor cell (NSPC) self-renewal and differentiation in the developing and the adult brain are controlled by extra-cellular signals and by the inherent competence of NSPCs to produce appropriate responses. Stage-dependent responsiveness of NSPCs to extrinsic cues is orchestrated at the epigenetic level. Epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNA-mediated regulation control crucial aspects of NSPC development and function, and are also implicated in pathological conditions. While their roles in the regulation of stem cell fate have been largely explored in pluripotent stem cell models, the epigenetic signature of NSPCs is also key to determine their multipotency as well as their progressive bias towards specific differentiation outcomes. Here we review recent developments in this field, focusing on the roles of histone methylation marks and the protein complexes controlling their deposition in NSPCs of the developing cerebral cortex and the adult subventricular zone. In this context, we describe how bivalent promoters, carrying antagonistic epigenetic modifications, feature during multiple steps of neural development, from neural lineage specification to neuronal differentiation. Furthermore, we discuss the emerging cross-talk between epigenetic regulators and microRNAs, and how the interplay between these different layers of regulation can finely tune the expression of genes controlling NSPC maintenance and differentiation. In particular, we highlight recent advances in the identification of astrocyte-enriched microRNAs and their function in cell fate choices of NSPCs differentiating towards glial lineages.

Applications of Mesenchymal Stem Cells and Neural Crest Cells in Craniofacial Skeletal Research

Directory of Open Access Journals (Sweden)

Satoru Morikawa

2016-01-01

Full Text Available Craniofacial skeletal tissues are composed of tooth and bone, together with nerves and blood vessels. This composite material is mainly derived from neural crest cells (NCCs. The neural crest is transient embryonic tissue present during neural tube formation whose cells have high potential for migration and differentiation. Thus, NCCs are promising candidates for craniofacial tissue regeneration; however, the clinical application of NCCs is hindered by their limited accessibility. In contrast, mesenchymal stem cells (MSCs are easily accessible in adults, have similar potential for self-renewal, and can differentiate into skeletal tissues, including bones and cartilage. Therefore, MSCs may represent good sources of stem cells for clinical use. MSCs are classically identified under adherent culture conditions, leading to contamination with other cell lineages. Previous studies have identified mouse- and human-specific MSC subsets using cell surface markers. Additionally, some studies have shown that a subset of MSCs is closely related to neural crest derivatives and endothelial cells. These MSCs may be promising candidates for regeneration of craniofacial tissues from the perspective of developmental fate. Here, we review the fundamental biology of MSCs in craniofacial research.

Cell fate determination dynamics in bacteria

Science.gov (United States)

Kuchina, Anna; Espinar, Lorena; Cagatay, Tolga; Garcia-Ojalvo, Jordi; Suel, Gurol

2010-03-01

The fitness of an organism depends on many processes that serve the purpose to adapt to changing environment in a robust and coordinated fashion. One example of such process is cellular fate determination. In the presence of a variety of alternative responses each cell adopting a particular fate represents a ``choice'' that must be tightly regulated to ensure the best survival strategy for the population taking into account the broad range of possible environmental challenges. We investigated this problem in the model organism B.Subtilis which under stress conditions differentiates terminally into highly resistant spores or initiates an alternative transient state of competence. The dynamics underlying cell fate choice remains largely unknown. We utilize quantitative fluorescent microscopy to track the activities of genes involved in these responses on a single-cell level. We explored the importance of temporal interactions between competing cell fates by re- engineering the differentiation programs. I will discuss how the precise dynamics of cellular ``decision-making'' governed by the corresponding biological circuits may enable cells to adjust to diverse environments and determine survival.

An Comparative Study of Jane Eyre's Fate and Tess's Fate from Femi-nist Viewpoint%An Comparative Study of Jane Eyre's Fate and Tess's Fate from Femi?nist Viewpoint

Institute of Scientific and Technical Information of China (English)

陈静; 何泠静

2017-01-01

In"Jane Eyre", Charlotte Bronte's masterpiece the heroine, Jane Eyre has fully reflected her self-esteem, equality, and pure personality, which are also reflected in her concept of love vividly. However, Thomas Hardy's Tess is poor and kind, but she does not have a complete love like Jane Eyre, and she is described by his criticism of the old moral character with good vir-tues in the traditional sense. She is a new image of modern feminism who suffered from the old moral sense and gradually has re-volt consciousness. From the feminism viewpoint, this paper attempts to analysis the causes of their different fate from different points and reveal the impact of social background on their fates.

MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis

Directory of Open Access Journals (Sweden)

Francisca F. Vasconcelos

2016-10-01

Full Text Available The generation of neurons from neural stem cells requires large-scale changes in gene expression that are controlled to a large extent by proneural transcription factors, such as Ascl1. While recent studies have characterized the differentiation genes activated by proneural factors, less is known on the mechanisms that suppress progenitor cell identity. Here, we show that Ascl1 induces the transcription factor MyT1 while promoting neuronal differentiation. We combined functional studies of MyT1 during neurogenesis with the characterization of its transcriptional program. MyT1 binding is associated with repression of gene transcription in neural progenitor cells. It promotes neuronal differentiation by counteracting the inhibitory activity of Notch signaling at multiple levels, targeting the Notch1 receptor and many of its downstream targets. These include regulators of the neural progenitor program, such as Hes1, Sox2, Id3, and Olig1. Thus, Ascl1 suppresses Notch signaling cell-autonomously via MyT1, coupling neuronal differentiation with repression of the progenitor fate.

Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis

OpenAIRE

Kawaguchi, Daichi; Furutachi, Shohei; Kawai, Hiroki; Hozumi, Katsuto; Gotoh, Yukiko

2013-01-01

Stem cells often divide asymmetrically to produce one stem cell and one differentiating cell, thus maintaining the stem cell pool. Although neural stem cells (NSCs) in the adult mouse subventricular zone have been suggested to divide asymmetrically, intrinsic cell fate determinants for asymmetric NSC division are largely unknown. Stem cell niches are important for stem cell maintenance, but the niche for the maintenance of adult quiescent NSCs has remained obscure. Here we show that the Notch...

Particle shape impacts export and fate in the ocean through interactions with the globally abundant appendicularian Oikopleura dioica.

Science.gov (United States)

Conley, Keats R; Sutherland, Kelly R

2017-01-01

Marine microbes exhibit highly varied, often non-spherical shapes that have functional significance for essential processes, including nutrient acquisition and sinking rates. There is a surprising absence of data, however, on how cell shape affects grazing, which is crucial for predicting the fate of oceanic carbon. We used synthetic spherical and prolate spheroid microbeads to isolate the effect of particle length-to-width ratios on grazing and fate in the ocean. Here we show that the shape of microbe-sized particles affects predation by the appendicularian Oikopleura dioica, a globally abundant marine grazer. Using incubation experiments, we demonstrate that shape affects how particles are retained in the house and that the minimum particle diameter is the key variable determining how particles are ingested. High-speed videography revealed the mechanism behind these results: microbe-sized spheroids oriented with the long axis parallel to fluid streamlines, matching the speed and tortuosity of spheres of equivalent width. Our results suggest that the minimum particle diameter determines how elongated prey interact with the feeding-filters of appendicularians, which may help to explain the prevalence of ellipsoidal cells in the ocean, since a cell's increased surface-to-volume ratio does not always increase predation. We provide the first evidence that grazing by appendicularians can cause non-uniform export of different shaped particles, thereby influencing particle fate.

Krox20 defines a subpopulation of cardiac neural crest cells contributing to arterial valves and bicuspid aortic valve.

Science.gov (United States)

Odelin, Gaëlle; Faure, Emilie; Coulpier, Fanny; Di Bonito, Maria; Bajolle, Fanny; Studer, Michèle; Avierinos, Jean-François; Charnay, Patrick; Topilko, Piotr; Zaffran, Stéphane

2018-01-03

Although cardiac neural crest cells are required at early stages of arterial valve development, their contribution during valvular leaflet maturation remains poorly understood. Here, we show in mouse that neural crest cells from pre-otic and post-otic regions make distinct contributions to the arterial valve leaflets. Genetic fate-mapping analysis of Krox20-expressing neural crest cells shows a large contribution to the borders and the interleaflet triangles of the arterial valves. Loss of Krox20 function results in hyperplastic aortic valve and partially penetrant bicuspid aortic valve formation. Similar defects are observed in neural crest Krox20 -deficient embryos. Genetic lineage tracing in Krox20 -/- mutant mice shows that endothelial-derived cells are normal, whereas neural crest-derived cells are abnormally increased in number and misplaced in the valve leaflets. In contrast, genetic ablation of Krox20 -expressing cells is not sufficient to cause an aortic valve defect, suggesting that adjacent cells can compensate this depletion. Our findings demonstrate a crucial role for Krox20 in arterial valve development and reveal that an excess of neural crest cells may be associated with bicuspid aortic valve. © 2018. Published by The Company of Biologists Ltd.

Cell fate in the Arabidopsis root meristem determined by directional signalling.

Science.gov (United States)

van den Berg, C; Willemsen, V; Hage, W; Weisbeek, P; Scheres, B

1995-11-02

Postembryonic development in plants is achieved by apical meristems. Surgical studies and clonal analysis have revealed indirectly that cells in shoot meristems have no predictable destiny and that position is likely to play a role in the acquisition of cell identity. In contrast to animal systems, there has been no direct evidence for inductive signalling in plants until now. Here we present evidence for such signalling using laser ablation of cells in the root meristem of Arabidopsis thaliana. Although these cells show rigid clonal relationships, we now demonstrate that it is positional control that is most important in the determination of cell fate. Positional signals can be perpetuated from more mature to initial cells to guide the pattern of meristem cell differentiation. This offers an alternative to the general opinion that meristems are the source of patterning information.

Fate of pollutants

International Nuclear Information System (INIS)

Chapta, S.C.; Boyer, J.M.

1990-01-01

A literature review is presented of the fate of pollutants in sediment and water systems. Topics of discussion include the following: modeling, observations, and general studies; chlorinated xenobiotic chemicals; nonchlorinated xenobiotic chemicals; pesticides; heavy metals; and radionuclides

Condition monitoring of planetary gearbox by hardware implementation of artificial neural networks

DEFF Research Database (Denmark)

Dabrowski, Dariusz

2016-01-01

for a selected neural network, which is based on a Learning Vector Quantization (LVQ) algorithm. Presented classifier can be used as an independent diagnostic system or can be combined with traditional data acquisition systems using FPGAs. (C) 2016 Elsevier Ltd. All rights reserved....

MicroRNA let-7d regulates the TLX/microRNA-9 cascade to control neural cell fate and neurogenesis.

Science.gov (United States)

Zhao, Chunnian; Sun, GuoQiang; Ye, Peng; Li, Shengxiu; Shi, Yanhong

2013-01-01

MicroRNAs have important functions in the nervous system through post-transcriptional regulation of neurogenesis genes. Here we show that microRNA let-7d, which has been implicated in cocaine addiction and other neurological disorders, targets the neural stem cell regulator TLX. Overexpression of let-7d in vivo reduced neural stem cell proliferation and promoted premature neuronal differentiation and migration, a phenotype similar to those induced by TLX knockdown or overexpression of its negatively-regulated target, microRNA-9. We found a let-7d binding sequence in the tlx 3' UTR and demonstrated that let-7d reduced TLX expression levels in neural stem cells, which in turn, up-regulated miR-9 expression. Moreover, co-expression of let-7d and TLX lacking its 3' UTR in vivo restored neural stem cell proliferation and reversed the premature neuronal differentiation and migration. Therefore, manipulating let-7d and its downstream targets could be a novel strategy to unravel neurogenic signaling pathways and identify potential interventions for relevant neurological disorders.

Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.

Science.gov (United States)

Pardanaud, Luc; Pibouin-Fragner, Laurence; Dubrac, Alexandre; Mathivet, Thomas; English, Isabel; Brunet, Isabelle; Simons, Michael; Eichmann, Anne

2016-08-19

Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood. We set out to identify factors that promote arterial endothelial cell fate in vivo. We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors. These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease. © 2016 American Heart Association, Inc.

Transcriptional profiling of adult neural stem-like cells from the human brain.

Directory of Open Access Journals (Sweden)

Cecilie Jonsgar Sandberg

Full Text Available There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60. Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate. We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6, foetal human neural stem cells (n = 1 and human brain tissues (n = 12. The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular

EEG-fMRI Bayesian framework for neural activity estimation: a simulation study

Science.gov (United States)

Croce, Pierpaolo; Basti, Alessio; Marzetti, Laura; Zappasodi, Filippo; Del Gratta, Cosimo

2016-12-01

Objective. Due to the complementary nature of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), and given the possibility of simultaneous acquisition, the joint data analysis can afford a better understanding of the underlying neural activity estimation. In this simulation study we want to show the benefit of the joint EEG-fMRI neural activity estimation in a Bayesian framework. Approach. We built a dynamic Bayesian framework in order to perform joint EEG-fMRI neural activity time course estimation. The neural activity is originated by a given brain area and detected by means of both measurement techniques. We have chosen a resting state neural activity situation to address the worst case in terms of the signal-to-noise ratio. To infer information by EEG and fMRI concurrently we used a tool belonging to the sequential Monte Carlo (SMC) methods: the particle filter (PF). Main results. First, despite a high computational cost, we showed the feasibility of such an approach. Second, we obtained an improvement in neural activity reconstruction when using both EEG and fMRI measurements. Significance. The proposed simulation shows the improvements in neural activity reconstruction with EEG-fMRI simultaneous data. The application of such an approach to real data allows a better comprehension of the neural dynamics.

Investigating undergraduate students' ideas about the fate of the Universe

Science.gov (United States)

Conlon, Mallory; Coble, Kim; Bailey, Janelle M.; Cominsky, Lynn R.

2017-12-01

As astronomers further develop an understanding of the fate of the Universe, it is essential to study students' ideas on the fate of the Universe so that instructors can communicate the field's current status more effectively. In this study, we examine undergraduate students' preinstruction ideas of the fate of the Universe in ten semester-long introductory astronomy course sections (ASTRO 101) at three institutions. We also examine students' postinstruction ideas about the fate of the Universe in ASTRO 101 over five semester-long course sections at one institution. The data include precourse surveys given during the first week of instruction (N =264 ), postinstruction exam questions (N =59 ), and interviews. We find that, preinstruction, more than a quarter of ASTRO 101 students either do not respond or respond with "I don't know" when asked what the long-term fate of the Universe is. We also find that, though the term was not necessarily used, students tend to describe a "big chill" scenario in the preinstruction surveys, among a wide variety of other scenarios. A fraction of students describe the fate of smaller-scale systems, possibly due to confusion of the hierarchical nature of structure in the Universe. Preinstruction, students mention the Universe's expansion when describing how astronomers know the fate of the Universe but do not discuss how we know the Universe is expanding or the relationship between expansion and the fate of the Universe. Postinstruction, students' responses shift toward greater degrees of completeness and correctness.

Transcriptional response of Hoxb genes to retinoid signalling is regionally restricted along the neural tube rostrocaudal axis.

Science.gov (United States)

Carucci, Nicoletta; Cacci, Emanuele; Nisi, Paola S; Licursi, Valerio; Paul, Yu-Lee; Biagioni, Stefano; Negri, Rodolfo; Rugg-Gunn, Peter J; Lupo, Giuseppe

2017-04-01

During vertebrate neural development, positional information is largely specified by extracellular morphogens. Their distribution, however, is very dynamic due to the multiple roles played by the same signals in the developing and adult neural tissue. This suggests that neural progenitors are able to modify their competence to respond to morphogen signalling and autonomously maintain positional identities after their initial specification. In this work, we take advantage of in vitro culture systems of mouse neural stem/progenitor cells (NSPCs) to show that NSPCs isolated from rostral or caudal regions of the mouse neural tube are differentially responsive to retinoic acid (RA), a pivotal morphogen for the specification of posterior neural fates. Hoxb genes are among the best known RA direct targets in the neural tissue, yet we found that RA could promote their transcription only in caudal but not in rostral NSPCs. Correlating with these effects, key RA-responsive regulatory regions in the Hoxb cluster displayed opposite enrichment of activating or repressing histone marks in rostral and caudal NSPCs. Finally, RA was able to strengthen Hoxb chromatin activation in caudal NSPCs, but was ineffective on the repressed Hoxb chromatin of rostral NSPCs. These results suggest that the response of NSPCs to morphogen signalling across the rostrocaudal axis of the neural tube may be gated by the epigenetic configuration of target patterning genes, allowing long-term maintenance of intrinsic positional values in spite of continuously changing extrinsic signals.

Neural redundancy applied to the parity space for signal validation

International Nuclear Information System (INIS)

Mol, Antonio Carlos de Abreu; Pereira, Claudio Marcio Nascimento Abreu; Martinez, Aquilino Senra

2005-01-01

The objective of signal validation is to provide more reliable information from the plant sensor data The method presented in this work introduces the concept of neural redundancy and applies it to the space parity method [1] to overcome an inherent deficiency of this method - the determination of the best estimative of the redundant measures when they are inconsistent. The concept of neural redundancy consists on the calculation of a redundancy through neural networks based on the time series of the own state variable. Therefore, neural networks, dynamically trained with the time series, will estimate the current value of the own measure, which will be used as referee of the redundant measures in the parity space. For this purpose the neural network should have the capacity to supply the neural redundancy in real time and with maximum error corresponding to the group deviation. The historical series should be enough to allow the estimate of the next value, during transients and at the same time, it should be optimized to facilitate the retraining of the neural network to each acquisition. In order to have the capacity to reproduce the tendency of the time series even under accident condition, the dynamic training of the neural network privileges the recent points of the time series. The tests accomplished with simulated data of a nuclear plant, demonstrated that this method applied on the parity space method improves the signal validation process. (author)

Neural redundancy applied to the parity space for signal validation

Energy Technology Data Exchange (ETDEWEB)

Mol, Antonio Carlos de Abreu; Pereira, Claudio Marcio Nascimento Abreu [Instituto de Engenharia Nuclear (IEN), Rio de Janeiro, RJ (Brazil)]. E-mail: cmnap@ien.gov.br; Martinez, Aquilino Senra [Universidade Federal, Rio de Janeiro, RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia]. E-mail: aquilino@lmp.br

2005-07-01

The objective of signal validation is to provide more reliable information from the plant sensor data The method presented in this work introduces the concept of neural redundancy and applies it to the space parity method [1] to overcome an inherent deficiency of this method - the determination of the best estimative of the redundant measures when they are inconsistent. The concept of neural redundancy consists on the calculation of a redundancy through neural networks based on the time series of the own state variable. Therefore, neural networks, dynamically trained with the time series, will estimate the current value of the own measure, which will be used as referee of the redundant measures in the parity space. For this purpose the neural network should have the capacity to supply the neural redundancy in real time and with maximum error corresponding to the group deviation. The historical series should be enough to allow the estimate of the next value, during transients and at the same time, it should be optimized to facilitate the retraining of the neural network to each acquisition. In order to have the capacity to reproduce the tendency of the time series even under accident condition, the dynamic training of the neural network privileges the recent points of the time series. The tests accomplished with simulated data of a nuclear plant, demonstrated that this method applied on the parity space method improves the signal validation process. (author)

Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo

Directory of Open Access Journals (Sweden)

Sophie R. Miller

2017-03-01

Full Text Available Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs, we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1 into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4. NotchΔE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells, but also neural crest-derived frontonasal mesenchyme and perhaps developing OECs, to a perivascular cell fate. These results also highlight the plasticity of neural crest-derived mesenchyme and glia.

An illusion of control modulates the reluctance to tempt fate

Directory of Open Access Journals (Sweden)

Chloe L. Swirsky

2011-10-01

Full Text Available The tempting fate effect is that the probability of a fateful outcome is deemed higher following an action that ``tempts'' the outcome than in the absence of such an action. In this paper we evaluate the hypothesis that the effect is due to an illusion of control induced by a causal framing of the situation. Causal frames require that the action make a difference to an outcome and that the action precedes the outcome. If an illusion of control modulates the reluctance to tempt fate, then actions that make a difference to well-being and that occur prior to the outcome should tempt fate most strongly. In Experiments 1--3 we varied whether the action makes a difference and the temporal order of action and outcome. In Experiment 4 we tested whether an action can tempt fate if all outcomes are negative. The results of all four experiments supported our hypothesis that the tempting fate effect depends on a causal construal that gives rise to a false sense of control.

MicroRNA-130b targets Fmr1 and regulates embryonic neural progenitor cell proliferation and differentiation

International Nuclear Information System (INIS)

Gong, Xi; Zhang, Kunshan; Wang, Yanlu; Wang, Junbang; Cui, Yaru; Li, Siguang; Luo, Yuping

2013-01-01

Highlights: •We found that the 3′ UTR of the Fmr1 mRNA is a target of miR-130b. •MiR-130b suppresses the expression of Fmr1 in mouse embryonic stem cell. •MiR-130b alters the proliferation of mouse embryonic stem cell. •MiR-130b alters fate specification of mouse embryonic stem cell. -- Abstract: Fragile X syndrome, one of the most common forms of inherited mental retardation, is caused by expansion of the CGG repeat in the 5′-untranslated region of the X-linked Fmr1 gene, which results in transcriptional silencing and loss of expression of its encoded protein FMRP. The loss of FMRP increases proliferation and alters fate specification in adult neural progenitor cells (aNPCs). However, little is known about Fmr1 mRNA regulation at the transcriptional and post-transcriptional levels. In the present study, we report that miR-130b regulated Fmr1 expression by directly targeting its 3′-untranslated region (3′ UTR). Up-regulation of miR-130b in mouse embryonic neural progenitor cells (eNPCs) decreased Fmr1 expression, markedly increased eNPC proliferation and altered the differentiation tendency of eNPCs, suggesting that antagonizing miR-130b may be a new therapeutic entry point for treating Fragile X syndrome

MicroRNA-130b targets Fmr1 and regulates embryonic neural progenitor cell proliferation and differentiation

Energy Technology Data Exchange (ETDEWEB)

Gong, Xi [State Key Laboratory of Food Science and Technology, College of Life Sciences and Food Engineering, Nanchang University, Nanchang 330047 (China); Zhang, Kunshan [Department of Regenerative Medicine, Stem Cell Center, Tongji University School of Medicine, Shanghai 200092 (China); Wang, Yanlu; Wang, Junbang; Cui, Yaru [State Key Laboratory of Food Science and Technology, College of Life Sciences and Food Engineering, Nanchang University, Nanchang 330047 (China); Li, Siguang, E-mail: siguangli@163.com [Department of Regenerative Medicine, Stem Cell Center, Tongji University School of Medicine, Shanghai 200092 (China); Luo, Yuping, E-mail: luoyuping@163.com [State Key Laboratory of Food Science and Technology, College of Life Sciences and Food Engineering, Nanchang University, Nanchang 330047 (China)

2013-10-04

Highlights: •We found that the 3′ UTR of the Fmr1 mRNA is a target of miR-130b. •MiR-130b suppresses the expression of Fmr1 in mouse embryonic stem cell. •MiR-130b alters the proliferation of mouse embryonic stem cell. •MiR-130b alters fate specification of mouse embryonic stem cell. -- Abstract: Fragile X syndrome, one of the most common forms of inherited mental retardation, is caused by expansion of the CGG repeat in the 5′-untranslated region of the X-linked Fmr1 gene, which results in transcriptional silencing and loss of expression of its encoded protein FMRP. The loss of FMRP increases proliferation and alters fate specification in adult neural progenitor cells (aNPCs). However, little is known about Fmr1 mRNA regulation at the transcriptional and post-transcriptional levels. In the present study, we report that miR-130b regulated Fmr1 expression by directly targeting its 3′-untranslated region (3′ UTR). Up-regulation of miR-130b in mouse embryonic neural progenitor cells (eNPCs) decreased Fmr1 expression, markedly increased eNPC proliferation and altered the differentiation tendency of eNPCs, suggesting that antagonizing miR-130b may be a new therapeutic entry point for treating Fragile X syndrome.

Multipotent versus differentiated cell fate selection in the developing Drosophila airways

Science.gov (United States)

Matsuda, Ryo; Hosono, Chie; Samakovlis, Christos; Saigo, Kaoru

2015-01-01

Developmental potentials of cells are tightly controlled at multiple levels. The embryonic Drosophila airway tree is roughly subdivided into two types of cells with distinct developmental potentials: a proximally located group of multipotent adult precursor cells (P-fate) and a distally located population of more differentiated cells (D-fate). We show that the GATA-family transcription factor (TF) Grain promotes the P-fate and the POU-homeobox TF Ventral veinless (Vvl/Drifter/U-turned) stimulates the D-fate. Hedgehog and receptor tyrosine kinase (RTK) signaling cooperate with Vvl to drive the D-fate at the expense of the P-fate while negative regulators of either of these signaling pathways ensure P-fate specification. Local concentrations of Decapentaplegic/BMP, Wingless/Wnt, and Hedgehog signals differentially regulate the expression of D-factors and P-factors to transform an equipotent primordial field into a concentric pattern of radially different morphogenetic potentials, which gradually gives rise to the distal-proximal organization of distinct cell types in the mature airway. DOI: http://dx.doi.org/10.7554/eLife.09646.001 PMID:26633813

Investigating undergraduate students’ ideas about the fate of the Universe

Directory of Open Access Journals (Sweden)

Mallory Conlon

2017-11-01

Full Text Available As astronomers further develop an understanding of the fate of the Universe, it is essential to study students’ ideas on the fate of the Universe so that instructors can communicate the field’s current status more effectively. In this study, we examine undergraduate students’ preinstruction ideas of the fate of the Universe in ten semester-long introductory astronomy course sections (ASTRO 101 at three institutions. We also examine students’ postinstruction ideas about the fate of the Universe in ASTRO 101 over five semester-long course sections at one institution. The data include precourse surveys given during the first week of instruction (N=264, postinstruction exam questions (N=59, and interviews. We find that, preinstruction, more than a quarter of ASTRO 101 students either do not respond or respond with “I don’t know” when asked what the long-term fate of the Universe is. We also find that, though the term was not necessarily used, students tend to describe a “big chill” scenario in the preinstruction surveys, among a wide variety of other scenarios. A fraction of students describe the fate of smaller-scale systems, possibly due to confusion of the hierarchical nature of structure in the Universe. Preinstruction, students mention the Universe’s expansion when describing how astronomers know the fate of the Universe but do not discuss how we know the Universe is expanding or the relationship between expansion and the fate of the Universe. Postinstruction, students’ responses shift toward greater degrees of completeness and correctness.

Online neural monitoring of statistical learning.

Science.gov (United States)

Batterink, Laura J; Paller, Ken A

2017-05-01

The extraction of patterns in the environment plays a critical role in many types of human learning, from motor skills to language acquisition. This process is known as statistical learning. Here we propose that statistical learning has two dissociable components: (1) perceptual binding of individual stimulus units into integrated composites and (2) storing those integrated representations for later use. Statistical learning is typically assessed using post-learning tasks, such that the two components are conflated. Our goal was to characterize the online perceptual component of statistical learning. Participants were exposed to a structured stream of repeating trisyllabic nonsense words and a random syllable stream. Online learning was indexed by an EEG-based measure that quantified neural entrainment at the frequency of the repeating words relative to that of individual syllables. Statistical learning was subsequently assessed using conventional measures in an explicit rating task and a reaction-time task. In the structured stream, neural entrainment to trisyllabic words was higher than in the random stream, increased as a function of exposure to track the progression of learning, and predicted performance on the reaction time (RT) task. These results demonstrate that monitoring this critical component of learning via rhythmic EEG entrainment reveals a gradual acquisition of knowledge whereby novel stimulus sequences are transformed into familiar composites. This online perceptual transformation is a critical component of learning. Copyright © 2017 Elsevier Ltd. All rights reserved.

Skeletogenic fate of zebrafish cranial and trunk neural crest.

Directory of Open Access Journals (Sweden)

Erika Kague

Full Text Available The neural crest (NC is a major contributor to the vertebrate craniofacial skeleton, detailed in model organisms through embryological and genetic approaches, most notably in chick and mouse. Despite many similarities between these rather distant species, there are also distinct differences in the contribution of the NC, particularly to the calvariae of the skull. Lack of information about other vertebrate groups precludes an understanding of the evolutionary significance of these differences. Study of zebrafish craniofacial development has contributed substantially to understanding of cartilage and bone formation in teleosts, but there is currently little information on NC contribution to the zebrafish skeleton. Here, we employ a two-transgene system based on Cre recombinase to genetically label NC in the zebrafish. We demonstrate NC contribution to cells in the cranial ganglia and peripheral nervous system known to be NC-derived, as well as to a subset of myocardial cells. The indelible labeling also enables us to determine NC contribution to late-forming bones, including the calvariae. We confirm suspected NC origin of cartilage and bones of the viscerocranium, including cartilages such as the hyosymplectic and its replacement bones (hymandibula and symplectic and membranous bones such as the opercle. The cleithrum develops at the border of NC and mesoderm, and as an ancestral component of the pectoral girdle was predicted to be a hybrid bone composed of both NC and mesoderm tissues. However, we find no evidence of a NC contribution to the cleithrum. Similarly, in the vault of the skull, the parietal bones and the caudal portion of the frontal bones show no evidence of NC contribution. We also determine a NC origin for caudal fin lepidotrichia; the presumption is that these are derived from trunk NC, demonstrating that these cells have the ability to form bone during normal vertebrate development.

Characterizing root response phenotypes by neural network analysis

OpenAIRE

Hatzig, Sarah V.; Schiessl, Sarah; Stahl, Andreas; Snowdon, Rod J.

2015-01-01

Roots play an immediate role as the interface for water acquisition. To improve sustainability in low-water environments, breeders of major crops must therefore pay closer attention to advantageous root phenotypes; however, the complexity of root architecture in response to stress can be difficult to quantify. Here, the Sholl method, an established technique from neurobiology used for the characterization of neural network anatomy, was adapted to more adequately describe root responses to osm...

Wind Turbine Fault Detection based on Artificial Neural Network Analysis of SCADA Data

DEFF Research Database (Denmark)

Herp, Jürgen; S. Nadimi, Esmaeil

2015-01-01

Slowly developing faults in wind turbine can, when not detected and fixed on time, cause severe damage and downtime. We are proposing a fault detection method based on Artificial Neural Networks (ANN) and the recordings from Supervisory Control and Data Acquisition (SCADA) systems installed in wind...

An Comparative Study of Jane Eyre's Fate and Tess's Fate from Femi?nist Viewpoint

Institute of Scientific and Technical Information of China (English)

CHEN Jing; HE Ling-jing

2017-01-01

In"Jane Eyre", Charlotte Bronte's masterpiece the heroine, Jane Eyre has fully reflected her self-esteem, equality, and pure personality, which are also reflected in her concept of love vividly. However, Thomas Hardy's Tess is poor and kind, but she does not have a complete love like Jane Eyre, and she is described by his criticism of the old moral character with good vir-tues in the traditional sense. She is a new image of modern feminism who suffered from the old moral sense and gradually has re-volt consciousness. From the feminism viewpoint, this paper attempts to analysis the causes of their different fate from different points and reveal the impact of social background on their fates.

Different cell fates from cell-cell interactions: core architectures of two-cell bistable networks.

Science.gov (United States)

Rouault, Hervé; Hakim, Vincent

2012-02-08

The acquisition of different fates by cells that are initially in the same state is central to development. Here, we investigate the possible structures of bistable genetic networks that can allow two identical cells to acquire different fates through cell-cell interactions. Cell-autonomous bistable networks have been previously sampled using an evolutionary algorithm. We extend this evolutionary procedure to take into account interactions between cells. We obtain a variety of simple bistable networks that we classify into major subtypes. Some have long been proposed in the context of lateral inhibition through the Notch-Delta pathway, some have been more recently considered and others appear to be new and based on mechanisms not previously considered. The results highlight the role of posttranscriptional interactions and particularly of protein complexation and sequestration, which can replace cooperativity in transcriptional interactions. Some bistable networks are entirely based on posttranscriptional interactions and the simplest of these is found to lead, upon a single parameter change, to oscillations in the two cells with opposite phases. We provide qualitative explanations as well as mathematical analyses of the dynamical behaviors of various created networks. The results should help to identify and understand genetic structures implicated in cell-cell interactions and differentiation. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Fgf8-related secondary organizers exert different polarizing planar instructions along the mouse anterior neural tube.

Science.gov (United States)

Crespo-Enriquez, Ivan; Partanen, Juha; Martinez, Salvador; Echevarria, Diego

2012-01-01

Early brain patterning depends on proper arrangement of positional information. This information is given by gradients of secreted signaling molecules (morphogens) detected by individual cells within the responding tissue, leading to specific fate decisions. Here we report that the morphogen FGF8 exerts initially a differential signal activity along the E9.5 mouse neural tube. We demonstrate that this polarizing activity codes by RAS-regulated ERK1/2 signaling and depends on the topographical location of the secondary organizers: the isthmic organizer (IsO) and the anterior neural ridge (anr) but not on zona limitans intrathalamica (zli). Our results suggest that Sprouty2, a negative modulator of RAS/ERK pathway, is important for regulating Fgf8 morphogenetic signal activity by controlling Fgf8-induced signaling pathways and positional information during early brain development.

Neural network Hilbert transform based filtered backprojection for fast inline x-ray inspection

Science.gov (United States)

Janssens, Eline; De Beenhouwer, Jan; Van Dael, Mattias; De Schryver, Thomas; Van Hoorebeke, Luc; Verboven, Pieter; Nicolai, Bart; Sijbers, Jan

2018-03-01

X-ray imaging is an important tool for quality control since it allows to inspect the interior of products in a non-destructive way. Conventional x-ray imaging, however, is slow and expensive. Inline x-ray inspection, on the other hand, can pave the way towards fast and individual quality control, provided that a sufficiently high throughput can be achieved at a minimal cost. To meet these criteria, an inline inspection acquisition geometry is proposed where the object moves and rotates on a conveyor belt while it passes a fixed source and detector. Moreover, for this acquisition geometry, a new neural-network-based reconstruction algorithm is introduced: the neural network Hilbert transform based filtered backprojection. The proposed algorithm is evaluated both on simulated and real inline x-ray data and has shown to generate high quality reconstructions of 400  ×  400 reconstruction pixels within 200 ms, thereby meeting the high throughput criteria.

Astrocytes Can Adopt Endothelial Cell Fates in a p53-Dependent Manner.

Science.gov (United States)

Brumm, Andrew J; Nunez, Stefanie; Doroudchi, Mehdi M; Kawaguchi, Riki; Duan, Jinhzu; Pellegrini, Matteo; Lam, Larry; Carmichael, S Thomas; Deb, Arjun; Hinman, Jason D

2017-08-01

Astrocytes respond to a variety of CNS injuries by cellular enlargement, process outgrowth, and upregulation of extracellular matrix proteins that function to prevent expansion of the injured region. This astrocytic response, though critical to the acute injury response, results in the formation of a glial scar that inhibits neural repair. Scar-forming cells (fibroblasts) in the heart can undergo mesenchymal-endothelial transition into endothelial cell fates following cardiac injury in a process dependent on p53 that can be modulated to augment cardiac repair. Here, we sought to determine whether astrocytes, as the primary scar-forming cell of the CNS, are able to undergo a similar cellular phenotypic transition and adopt endothelial cell fates. Serum deprivation of differentiated astrocytes resulted in a change in cellular morphology and upregulation of endothelial cell marker genes. In a tube formation assay, serum-deprived astrocytes showed a substantial increase in vessel-like morphology that was comparable to human umbilical vein endothelial cells and dependent on p53. RNA sequencing of serum-deprived astrocytes demonstrated an expression profile that mimicked an endothelial rather than astrocyte transcriptome and identified p53 and angiogenic pathways as specifically upregulated. Inhibition of p53 with genetic or pharmacologic strategies inhibited astrocyte-endothelial transition. Astrocyte-endothelial cell transition could also be modulated by miR-194, a microRNA downstream of p53 that affects expression of genes regulating angiogenesis. Together, these studies demonstrate that differentiated astrocytes retain a stimulus-dependent mechanism for cellular transition into an endothelial phenotype that may modulate formation of the glial scar and promote injury-induced angiogenesis.

The novel BTB/POZ and zinc finger factor Zbtb45 is essential for proper glial differentiation of neural and oligodendrocyte progenitor cells

DEFF Research Database (Denmark)

Södersten, Erik; Lilja, Tobias; Hermanson, Ola

2010-01-01

Understanding the regulatory mechanisms controlling the fate decisions of neural stem cells (NSCs) is a crucial issue to shed new light on mammalian central nervous system (CNS) development in health and disease. We have investigated a possible role for the previously uncharacterized BTB/POZ-doma......Understanding the regulatory mechanisms controlling the fate decisions of neural stem cells (NSCs) is a crucial issue to shed new light on mammalian central nervous system (CNS) development in health and disease. We have investigated a possible role for the previously uncharacterized BTB....../POZ-domain containing zinc finger factor Zbtb45 in the differentiation of NSCs and postnatal oligodendrocyte precursors. In situ hybridization histochemistry and RT-qPCR analysis revealed that Zbtb45 mRNA was ubiquitously expressed in the developing CNS in mouse embryos at embryonic day (E) 12.5 and 14.5. Zbtb45 m......RNA knockdown in embryonic forebrain NSCs by siRNA resulted in a rapid decrease in the expression of oligodendrocyte-characteristic genes after mitogen (FGF2) withdrawal, whereas the expression of astrocyte-associated genes such as CD44 and GFAP increased compared to control. Accordingly, the number...

Neurogenesis and Increase in Differentiated Neural Cell Survival via Phosphorylation of Akt1 after Fluoxetine Treatment of Stem Cells

Directory of Open Access Journals (Sweden)

Anahita Rahmani

2013-01-01

Full Text Available Fluoxetine (FLX is a selective serotonin reuptake inhibitor (SSRI. Its action is possibly through an increase in neural cell survival. The mechanism of improved survival rate of neurons by FLX may relate to the overexpression of some kinases such as Akt protein. Akt1 (a serine/threonine kinase plays a key role in the modulation of cell proliferation and survival. Our study evaluated the effects of FLX on mesenchymal stem cell (MSC fate and Akt1 phosphorylation levels in MSCs. Evaluation tests included reverse transcriptase polymerase chain reaction, western blot, and immunocytochemistry assays. Nestin, MAP-2, and β-tubulin were detected after neurogenesis as neural markers. Ten μM of FLX upregulated phosphorylation of Akt1 protein in induced hEnSC significantly. Also FLX did increase viability of these MSCs. Continuous FLX treatment after neurogenesis elevated the survival rate of differentiated neural cells probably by enhanced induction of Akt1 phosphorylation. This study addresses a novel role of FLX in neurogenesis and differentiated neural cell survival that may contribute to explaining the therapeutic action of fluoxetine in regenerative pharmacology.

Modelling the fate of organic micropollutants in stormwater ponds

DEFF Research Database (Denmark)

Vezzaro, Luca; Eriksson, Eva; Ledin, Anna

2011-01-01

). The four simulated organic stormwater MP (iodopropynyl butylcarbamate — IPBC, benzene, glyphosate and pyrene) were selected according to their different urban sources and environmental fate. This ensures that the results can be extended to other relevant stormwater pollutants. All three models use......Urban water managers need to estimate the potential removal of organic micropollutants (MP) in stormwater treatment systems to support MP pollution control strategies. This study documents how the potential removal of organic MP in stormwater treatment systems can be quantified by using multimedia...... models. The fate of four different MP in a stormwater retention pond was simulated by applying two steady-state multimedia fate models (EPI Suite and SimpleBox) commonly applied in chemical risk assessment and a dynamic multimedia fate model (Stormwater Treatment Unit Model for Micro Pollutants — STUMP...

A regulatory transcriptional loop controls proliferation and differentiation in Drosophila neural stem cells.

Directory of Open Access Journals (Sweden)

Tetsuo Yasugi

Full Text Available Neurogenesis is initiated by a set of basic Helix-Loop-Helix (bHLH transcription factors that specify neural progenitors and allow them to generate neurons in multiple rounds of asymmetric cell division. The Drosophila Daughterless (Da protein and its mammalian counterparts (E12/E47 act as heterodimerization factors for proneural genes and are therefore critically required for neurogenesis. Here, we demonstrate that Da can also be an inhibitor of the neural progenitor fate whose absence leads to stem cell overproliferation and tumor formation. We explain this paradox by demonstrating that Da induces the differentiation factor Prospero (Pros whose asymmetric segregation is essential for differentiation in one of the two daughter cells. Da co-operates with the bHLH transcription factor Asense, whereas the other proneural genes are dispensible. After mitosis, Pros terminates Asense expression in one of the two daughter cells. In da mutants, pros is not expressed, leading to the formation of lethal transplantable brain tumors. Our results define a transcriptional feedback loop that regulates the balance between self-renewal and differentiation in Drosophila optic lobe neuroblasts. They indicate that initiation of a neural differentiation program in stem cells is essential to prevent tumorigenesis.

Direct Neural Conversion from Human Fibroblasts Using Self-Regulating and Nonintegrating Viral Vectors

Directory of Open Access Journals (Sweden)

Shong Lau

2014-12-01

Full Text Available Summary: Recent findings show that human fibroblasts can be directly programmed into functional neurons without passing via a proliferative stem cell intermediate. These findings open up the possibility of generating subtype-specific neurons of human origin for therapeutic use from fetal cell, from patients themselves, or from matched donors. In this study, we present an improved system for direct neural conversion of human fibroblasts. The neural reprogramming genes are regulated by the neuron-specific microRNA, miR-124, such that each cell turns off expression of the reprogramming genes once the cell has reached a stable neuronal fate. The regulated system can be combined with integrase-deficient vectors, providing a nonintegrative and self-regulated conversion system that rids problems associated with the integration of viral transgenes into the host genome. These modifications make the system suitable for clinical use and therefore represent a major step forward in the development of induced neurons for cell therapy. : Lau et al. now use miRNA targeting to build a self-regulating neural conversion system. Combined with nonintegrating vectors, this system can efficiently drive conversion of human fibroblasts into functional induced neurons (iNs suitable for clinical applications.

Asymmetric cell division during T cell development controls downstream fate

Science.gov (United States)

Pham, Kim; Shimoni, Raz; Charnley, Mirren; Ludford-Menting, Mandy J.; Hawkins, Edwin D.; Ramsbottom, Kelly; Oliaro, Jane; Izon, David; Ting, Stephen B.; Reynolds, Joseph; Lythe, Grant; Molina-Paris, Carmen; Melichar, Heather; Robey, Ellen; Humbert, Patrick O.; Gu, Min

2015-01-01

During mammalian T cell development, the requirement for expansion of many individual T cell clones, rather than merely expansion of the entire T cell population, suggests a possible role for asymmetric cell division (ACD). We show that ACD of developing T cells controls cell fate through differential inheritance of cell fate determinants Numb and α-Adaptin. ACD occurs specifically during the β-selection stage of T cell development, and subsequent divisions are predominantly symmetric. ACD is controlled by interaction with stromal cells and chemokine receptor signaling and uses a conserved network of polarity regulators. The disruption of polarity by deletion of the polarity regulator, Scribble, or the altered inheritance of fate determinants impacts subsequent fate decisions to influence the numbers of DN4 cells arising after the β-selection checkpoint. These findings indicate that ACD enables the thymic microenvironment to orchestrate fate decisions related to differentiation and self-renewal. PMID:26370500

Large-scale multielectrode recording and stimulation of neural activity

International Nuclear Information System (INIS)

Sher, A.; Chichilnisky, E.J.; Dabrowski, W.; Grillo, A.A.; Grivich, M.; Gunning, D.; Hottowy, P.; Kachiguine, S.; Litke, A.M.; Mathieson, K.; Petrusca, D.

2007-01-01

Large circuits of neurons are employed by the brain to encode and process information. How this encoding and processing is carried out is one of the central questions in neuroscience. Since individual neurons communicate with each other through electrical signals (action potentials), the recording of neural activity with arrays of extracellular electrodes is uniquely suited for the investigation of this question. Such recordings provide the combination of the best spatial (individual neurons) and temporal (individual action-potentials) resolutions compared to other large-scale imaging methods. Electrical stimulation of neural activity in turn has two very important applications: it enhances our understanding of neural circuits by allowing active interactions with them, and it is a basis for a large variety of neural prosthetic devices. Until recently, the state-of-the-art in neural activity recording systems consisted of several dozen electrodes with inter-electrode spacing ranging from tens to hundreds of microns. Using silicon microstrip detector expertise acquired in the field of high-energy physics, we created a unique neural activity readout and stimulation framework that consists of high-density electrode arrays, multi-channel custom-designed integrated circuits, a data acquisition system, and data-processing software. Using this framework we developed a number of neural readout and stimulation systems: (1) a 512-electrode system for recording the simultaneous activity of as many as hundreds of neurons, (2) a 61-electrode system for electrical stimulation and readout of neural activity in retinas and brain-tissue slices, and (3) a system with telemetry capabilities for recording neural activity in the intact brain of awake, naturally behaving animals. We will report on these systems, their various applications to the field of neurobiology, and novel scientific results obtained with some of them. We will also outline future directions

Fate of Pyrethroids in Farmland Ponds

DEFF Research Database (Denmark)

Mogensen, B. B.; Sørensen, P. B.; Stuer-Lauridsen, F.

Pyrethroids constitute a group of widely used insecticides, which are toxic to aquatic organisms. This report presents the results from a 2-year study of the fate of pyrethroids in ponds, i.e. their distribution in the water column, the sediment and the surface microlayer respectively. The measur......Pyrethroids constitute a group of widely used insecticides, which are toxic to aquatic organisms. This report presents the results from a 2-year study of the fate of pyrethroids in ponds, i.e. their distribution in the water column, the sediment and the surface microlayer respectively...

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.

Synthetic RNA Controllers for Programming Mammalian Cell Fate and Function

Science.gov (United States)

2015-11-04

Final report for “Synthetic RNA controllers for programming mammalian cell fate and function” Principal Investigator: Christina D. Smolke...SUBTITLE Synthetic RNA controllers for programming mammalian cell fate and function 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18   2 Synthetic RNA controllers for programming mammalian cell fate and function Task 1

Assessing the transport and fate of bioengineered microorganisms in the environment

International Nuclear Information System (INIS)

Barnthouse, L.W.; Palumbo, A.V.

1985-01-01

We review the methods currently available for quantifying the transport and fate of microbes in atmospheric and aqueous media and assess their adequacy for purposes of risk assessment. We review the literature on transport and fate of microorganisms, including studies of: (1) pathways of migration, (2) the survival of microorganisms during transport and fate. In addition, we review the transport and fate models that have been used in environmental risk assessments for radionuclides and toxic chemicals and evaluate their applicability to the problem of assessing environmental risks of bioengineered microorganisms

Stochastic Cell Fate Progression in Embryonic Stem Cells

Science.gov (United States)

Zou, Ling-Nan; Doyle, Adele; Jang, Sumin; Ramanathan, Sharad

2013-03-01

Studies on the directed differentiation of embryonic stem (ES) cells suggest that some early developmental decisions may be stochastic in nature. To identify the sources of this stochasticity, we analyzed the heterogeneous expression of key transcription factors in single ES cells as they adopt distinct germ layer fates. We find that under sufficiently stringent signaling conditions, the choice of lineage is unambiguous. ES cells flow into differentiated fates via diverging paths, defined by sequences of transitional states that exhibit characteristic co-expression of multiple transcription factors. These transitional states have distinct responses to morphogenic stimuli; by sequential exposure to multiple signaling conditions, ES cells are steered towards specific fates. However, the rate at which cells travel down a developmental path is stochastic: cells exposed to the same signaling condition for the same amount of time can populate different states along the same path. The heterogeneity of cell states seen in our experiments therefore does not reflect the stochastic selection of germ layer fates, but the stochastic rate of progression along a chosen developmental path. Supported in part by the Jane Coffin Childs Fund

Neural networks used to monitor an experimental test workbench

Energy Technology Data Exchange (ETDEWEB)

Moraes, Davi Almeida; Pereira, Iraci Martinez, E-mail: dmoraes@dk8.com.br, E-mail: martinez@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2017-07-01

This work presents the application of neural networks in an experimental workbench. This bench was developed with the purpose of conducting real time tests and data acquisition. The method applied for this work allowed to generate faulty data in a gradual and controlled way through the binary combination of double action valves. Using the SCADA application (Supervisory Control and Data Acquisition), it became possible to acquire data for analysis in Matlab / Simulink software. This bench has two reservoirs: a reservoir that has sensors for recording pressure and temperature variables for later analysis, and another reservoir that has level sensors. Four models were used to develop the respective practical experiments. In the first model, it was possible to perform all practical tests of the plant, as well as mechanical changes like repositioning of some mechanical components, piping, sensors and electrovalves. In the second model, it was noticed that the positioning of the flow meter, located after the pump output, prevented a good measurement of the flow variable. In the third model, it was perceived that the number of failures initially adopted, made the data too confusing for the neural network analysis. In the last model, it was possible to obtain a performance of 96.6% of hits after the reconfiguration for 4 controlled faults. (author)

Neural networks used to monitor an experimental test workbench

International Nuclear Information System (INIS)

Moraes, Davi Almeida; Pereira, Iraci Martinez

2017-01-01

This work presents the application of neural networks in an experimental workbench. This bench was developed with the purpose of conducting real time tests and data acquisition. The method applied for this work allowed to generate faulty data in a gradual and controlled way through the binary combination of double action valves. Using the SCADA application (Supervisory Control and Data Acquisition), it became possible to acquire data for analysis in Matlab / Simulink software. This bench has two reservoirs: a reservoir that has sensors for recording pressure and temperature variables for later analysis, and another reservoir that has level sensors. Four models were used to develop the respective practical experiments. In the first model, it was possible to perform all practical tests of the plant, as well as mechanical changes like repositioning of some mechanical components, piping, sensors and electrovalves. In the second model, it was noticed that the positioning of the flow meter, located after the pump output, prevented a good measurement of the flow variable. In the third model, it was perceived that the number of failures initially adopted, made the data too confusing for the neural network analysis. In the last model, it was possible to obtain a performance of 96.6% of hits after the reconfiguration for 4 controlled faults. (author)

High content screening of defined chemical libraries using normal and glioma-derived neural stem cell lines.

Science.gov (United States)

Danovi, Davide; Folarin, Amos A; Baranowski, Bart; Pollard, Steven M

2012-01-01

Small molecules with potent biological effects on the fate of normal and cancer-derived stem cells represent both useful research tools and new drug leads for regenerative medicine and oncology. Long-term expansion of mouse and human neural stem cells is possible using adherent monolayer culture. These cultures represent a useful cellular resource to carry out image-based high content screening of small chemical libraries. Improvements in automated microscopy, desktop computational power, and freely available image processing tools, now means that such chemical screens are realistic to undertake in individual academic laboratories. Here we outline a cost effective and versatile time lapse imaging strategy suitable for chemical screening. Protocols are described for the handling and screening of human fetal Neural Stem (NS) cell lines and their malignant counterparts, Glioblastoma-derived neural stem cells (GNS). We focus on identification of cytostatic and cytotoxic "hits" and discuss future possibilities and challenges for extending this approach to assay lineage commitment and differentiation. Copyright © 2012 Elsevier Inc. All rights reserved.

Investigating Undergraduate Students' Ideas about the Fate of the Universe

Science.gov (United States)

Conlon, Mallory; Coble, Kim; Bailey, Janelle M.; Cominsky, Lynn R.

2017-01-01

As astronomers further develop an understanding of the fate of the Universe, it is essential to study students' ideas on the fate of the Universe so that instructors can communicate the field's current status more effectively. In this study, we examine undergraduate students' preinstruction ideas of the fate of the Universe in ten semester-long…

Redox Regulation of Endothelial Cell Fate

Science.gov (United States)

Song, Ping; Zou, Ming-Hui

2014-01-01

Endothelial cells (ECs) are present throughout blood vessels and have variable roles in both physiological and pathological settings. EC fate is altered and regulated by several key factors in physiological or pathological conditions. Reactive nitrogen species and reactive oxygen species derived from NAD(P)H oxidases, mitochondria, or nitric oxide-producing enzymes are not only cytotoxic but also compose a signaling network in the redox system. The formation, actions, key molecular interactions, and physiological and pathological relevance of redox signals in ECs remain unclear. We review the identities, sources, and biological actions of oxidants and reductants produced during EC function or dysfunction. Further, we discuss how ECs shape key redox sensors and examine the biological functions, transcriptional responses, and post-translational modifications evoked by the redox system in ECs. We summarize recent findings regarding the mechanisms by which redox signals regulate the fate of ECs and address the outcome of altered EC fate in health and disease. Future studies will examine if the redox biology of ECs can be targeted in pathophysiological conditions. PMID:24633153

Neural Conversion and Patterning of Human Pluripotent Stem Cells: A Developmental Perspective.

Science.gov (United States)

Zirra, Alexandra; Wiethoff, Sarah; Patani, Rickie

2016-01-01

Since the reprogramming of adult human terminally differentiated somatic cells into induced pluripotent stem cells (hiPSCs) became a reality in 2007, only eight years have passed. Yet over this relatively short period, myriad experiments have revolutionized previous stem cell dogmata. The tremendous promise of hiPSC technology for regenerative medicine has fuelled rising expectations from both the public and scientific communities alike. In order to effectively harness hiPSCs to uncover fundamental mechanisms of disease, it is imperative to first understand the developmental neurobiology underpinning their lineage restriction choices in order to predictably manipulate cell fate to desired derivatives. Significant progress in developmental biology provides an invaluable resource for rationalising directed differentiation of hiPSCs to cellular derivatives of the nervous system. In this paper we begin by reviewing core developmental concepts underlying neural induction in order to provide context for how such insights have guided reductionist in vitro models of neural conversion from hiPSCs. We then discuss early factors relevant in neural patterning, again drawing upon crucial knowledge gained from developmental neurobiological studies. We conclude by discussing open questions relating to these concepts and how their resolution might serve to strengthen the promise of pluripotent stem cells in regenerative medicine.

Neural Conversion and Patterning of Human Pluripotent Stem Cells: A Developmental Perspective

Directory of Open Access Journals (Sweden)

Alexandra Zirra

2016-01-01

Full Text Available Since the reprogramming of adult human terminally differentiated somatic cells into induced pluripotent stem cells (hiPSCs became a reality in 2007, only eight years have passed. Yet over this relatively short period, myriad experiments have revolutionized previous stem cell dogmata. The tremendous promise of hiPSC technology for regenerative medicine has fuelled rising expectations from both the public and scientific communities alike. In order to effectively harness hiPSCs to uncover fundamental mechanisms of disease, it is imperative to first understand the developmental neurobiology underpinning their lineage restriction choices in order to predictably manipulate cell fate to desired derivatives. Significant progress in developmental biology provides an invaluable resource for rationalising directed differentiation of hiPSCs to cellular derivatives of the nervous system. In this paper we begin by reviewing core developmental concepts underlying neural induction in order to provide context for how such insights have guided reductionist in vitro models of neural conversion from hiPSCs. We then discuss early factors relevant in neural patterning, again drawing upon crucial knowledge gained from developmental neurobiological studies. We conclude by discussing open questions relating to these concepts and how their resolution might serve to strengthen the promise of pluripotent stem cells in regenerative medicine.

The lamprey: a jawless vertebrate model system for examining origin of the neural crest and other vertebrate traits.

Science.gov (United States)

Green, Stephen A; Bronner, Marianne E

2014-01-01

Lampreys are a group of jawless fishes that serve as an important point of comparison for studies of vertebrate evolution. Lampreys and hagfishes are agnathan fishes, the cyclostomes, which sit at a crucial phylogenetic position as the only living sister group of the jawed vertebrates. Comparisons between cyclostomes and jawed vertebrates can help identify shared derived (i.e. synapomorphic) traits that might have been inherited from ancestral early vertebrates, if unlikely to have arisen convergently by chance. One example of a uniquely vertebrate trait is the neural crest, an embryonic tissue that produces many cell types crucial to vertebrate features, such as the craniofacial skeleton, pigmentation of the skin, and much of the peripheral nervous system (Gans and Northcutt, 1983). Invertebrate chordates arguably lack unambiguous neural crest homologs, yet have cells with some similarities, making comparisons with lampreys and jawed vertebrates essential for inferring characteristics of development in early vertebrates, and how they may have evolved from nonvertebrate chordates. Here we review recent research on cyclostome neural crest development, including research on lamprey gene regulatory networks and differentiated neural crest fates. Copyright © 2014 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Specifying pancreatic endocrine cell fates.

Science.gov (United States)

Collombat, Patrick; Hecksher-Sørensen, Jacob; Serup, Palle; Mansouri, Ahmed

2006-07-01

Cell replacement therapy could represent an attractive alternative to insulin injections for the treatment of diabetes. However, this approach requires a thorough understanding of the molecular switches controlling the specification of the different pancreatic cell-types in vivo. These are derived from an apparently identical pool of cells originating from the early gut endoderm, which are successively specified towards the pancreatic, endocrine, and hormone-expressing cell lineages. Numerous studies have outlined the crucial roles exerted by transcription factors in promoting the cell destiny, defining the cell identity and maintaining a particular cell fate. This review focuses on the mechanisms regulating the morphogenesis of the pancreas with particular emphasis on recent findings concerning the transcription factor hierarchy orchestrating endocrine cell fate allocation.

Semi-empirical neural network models of controlled dynamical systems

Directory of Open Access Journals (Sweden)

Mihail V. Egorchev

2017-12-01

Full Text Available A simulation approach is discussed for maneuverable aircraft motion as nonlinear controlled dynamical system under multiple and diverse uncertainties including knowledge imperfection concerning simulated plant and its environment exposure. The suggested approach is based on a merging of theoretical knowledge for the plant with training tools of artificial neural network field. The efficiency of this approach is demonstrated using the example of motion modeling and the identification of the aerodynamic characteristics of a maneuverable aircraft. A semi-empirical recurrent neural network based model learning algorithm is proposed for multi-step ahead prediction problem. This algorithm sequentially states and solves numerical optimization subproblems of increasing complexity, using each solution as initial guess for subsequent subproblem. We also consider a procedure for representative training set acquisition that utilizes multisine control signals.

Global fate of POPs: Current and future research directions

International Nuclear Information System (INIS)

Lohmann, Rainer; Breivik, Knut; Dachs, Jordi; Muir, Derek

2007-01-01

For legacy and emerging persistent organic pollutants (POPs), surprisingly little is still known in quantitative terms about their global sources and emissions. Atmospheric transport has been identified as the key global dispersal mechanism for most legacy POPs. In contrast, transport by ocean currents may prove to be the main transport route for many polar, emerging POPs. This is linked to the POPs' intrinsic physico-chemical properties, as exemplified by the different fate of hexachlorocyclohexanes in the Arctic. Similarly, our current understanding of POPs' global transport and fate remains sketchy. The importance of organic carbon and global temperature differences have been accepted as key drivers of POPs' global distribution. However, future research will need to understand the various biogeochemical and geophysical cycles under anthropogenic pressures to be able to understand and predict the global fate of POPs accurately. - Future studies into the global fate of POPs will need to pay more attention to the various biogeochemical and anthropogenic cycles to better understand emissions, transport and sinks

Effect of composting on the fate of steroids in beef cattle manure

Science.gov (United States)

In this study, the fate of steroid hormones in beef cattle manure composting is evaluated. The fate of 16 steroids and metabolites was evaluated in composted manure from beef cattle administered growth promotants and from beef cattle with no steroid hormone implants. The fate of estrogens (primary...

A Fully Integrated Wireless Compressed Sensing Neural Signal Acquisition System for Chronic Recording and Brain Machine Interface.

Science.gov (United States)

Liu, Xilin; Zhang, Milin; Xiong, Tao; Richardson, Andrew G; Lucas, Timothy H; Chin, Peter S; Etienne-Cummings, Ralph; Tran, Trac D; Van der Spiegel, Jan

2016-07-18

Reliable, multi-channel neural recording is critical to the neuroscience research and clinical treatment. However, most hardware development of fully integrated, multi-channel wireless neural recorders to-date, is still in the proof-of-concept stage. To be ready for practical use, the trade-offs between performance, power consumption, device size, robustness, and compatibility need to be carefully taken into account. This paper presents an optimized wireless compressed sensing neural signal recording system. The system takes advantages of both custom integrated circuits and universal compatible wireless solutions. The proposed system includes an implantable wireless system-on-chip (SoC) and an external wireless relay. The SoC integrates 16-channel low-noise neural amplifiers, programmable filters and gain stages, a SAR ADC, a real-time compressed sensing module, and a near field wireless power and data transmission link. The external relay integrates a 32 bit low-power microcontroller with Bluetooth 4.0 wireless module, a programming interface, and an inductive charging unit. The SoC achieves high signal recording quality with minimized power consumption, while reducing the risk of infection from through-skin connectors. The external relay maximizes the compatibility and programmability. The proposed compressed sensing module is highly configurable, featuring a SNDR of 9.78 dB with a compression ratio of 8×. The SoC has been fabricated in a 180 nm standard CMOS technology, occupying 2.1 mm × 0.6 mm silicon area. A pre-implantable system has been assembled to demonstrate the proposed paradigm. The developed system has been successfully used for long-term wireless neural recording in freely behaving rhesus monkey.

Epigenetic regulation of neural stem cell property from embryo to adult

Directory of Open Access Journals (Sweden)

Naoya Murao

2016-03-01

Full Text Available Neural stem cells (NSCs have the ability to self-renew and give rise to neurons and glial cells (astrocytes and oligodendrocytes in the mammalian central nervous system. This multipotency is acquired by NSCs during development and is maintained throughout life. Proliferation, fate specification, and maturation of NSCs are regulated by both cell intrinsic and extrinsic factors. Epigenetic modification is a representative intrinsic factor, being involved in many biological aspects of central nervous system development and adult neurogenesis through the regulation of NSC dynamics. In this review, we summarize recent progress in the epigenetic regulation of NSC behavior in the embryonic and adult brain, with particular reference to DNA methylation, histone modification, and noncoding RNAs.

Ca(2+) coding and decoding strategies for the specification of neural and renal precursor cells during development.

Science.gov (United States)

Moreau, Marc; Néant, Isabelle; Webb, Sarah E; Miller, Andrew L; Riou, Jean-François; Leclerc, Catherine

2016-03-01

During embryogenesis, a rise in intracellular Ca(2+) is known to be a widespread trigger for directing stem cells towards a specific tissue fate, but the precise Ca(2+) signalling mechanisms involved in achieving these pleiotropic effects are still poorly understood. In this review, we compare the Ca(2+) signalling events that appear to be one of the first steps in initiating and regulating both neural determination (neural induction) and kidney development (nephrogenesis). We have highlighted the necessary and sufficient role played by Ca(2+) influx and by Ca(2+) transients in the determination and differentiation of pools of neural or renal precursors. We have identified new Ca(2+) target genes involved in neural induction and we showed that the same Ca(2+) early target genes studied are not restricted to neural tissue but are also present in other tissues, principally in the pronephros. In this review, we also described a mechanism whereby the transcriptional control of gene expression during neurogenesis and nephrogenesis might be directly controlled by Ca(2+) signalling. This mechanism involves members of the Kcnip family such that a change in their binding properties to specific DNA sites is a result of Ca(2+) binding to EF-hand motifs. The different functions of Ca(2+) signalling during these two events illustrate the versatility of Ca(2+) as a second messenger. Copyright © 2015 Elsevier Ltd. All rights reserved.

BETR global - A geographically-explicit global-scale multimedia contaminant fate model

International Nuclear Information System (INIS)

MacLeod, Matthew; Waldow, Harald von; Tay, Pascal; Armitage, James M.; Woehrnschimmel, Henry; Riley, William J.; McKone, Thomas E.; Hungerbuhler, Konrad

2011-01-01

We present two new software implementations of the BETR Global multimedia contaminant fate model. The model uses steady-state or non-steady-state mass-balance calculations to describe the fate and transport of persistent organic pollutants using a desktop computer. The global environment is described using a database of long-term average monthly conditions on a 15 o x 15 o grid. We demonstrate BETR Global by modeling the global sources, transport, and removal of decamethylcyclopentasiloxane (D5). - Two new software implementations of the Berkeley-Trent Global Contaminant Fate Model are available. The new model software is illustrated using a case study of the global fate of decamethylcyclopentasiloxane (D5).

Nestin-positive mesenchymal stem cells favour the astroglial lineage in neural progenitors and stem cells by releasing active BMP4

Directory of Open Access Journals (Sweden)

Leprince Pierre

2004-09-01

Full Text Available Abstract Background Spontaneous repair is limited after CNS injury or degeneration because neurogenesis and axonal regrowth rarely occur in the adult brain. As a result, cell transplantation has raised much interest as potential treatment for patients with CNS lesions. Several types of cells have been considered as candidates for such cell transplantation and replacement therapies. Foetal brain tissue has already been shown to have significant effects in patients with Parkinson's disease. Clinical use of the foetal brain tissue is, however, limited by ethical and technical problems as it requires high numbers of grafted foetal cells and immunosuppression. Alternatively, several reports suggested that mesenchymal stem cells, isolated from adult bone marrow, are multipotent cells and could be used in autograft approach for replacement therapies. Results In this study, we addressed the question of the possible influence of mesenchymal stem cells on neural stem cell fate. We have previously reported that adult rat mesenchymal stem cells are able to express nestin in defined culture conditions (in the absence of serum and after 25 cell population doublings and we report here that nestin-positive (but not nestin-negative mesenchymal stem cells are able to favour the astroglial lineage in neural progenitors and stem cells cultivated from embryonic striatum. The increase of the number of GFAP-positive cells is associated with a significant decrease of the number of Tuj1- and O4-positive cells. Using quantitative RT-PCR, we demonstrate that mesenchymal stem cells express LIF, CNTF, BMP2 and BMP4 mRNAs, four cytokines known to play a role in astroglial fate decision. In this model, BMP4 is responsible for the astroglial stimulation and oligodendroglial inhibition, as 1 this cytokine is present in a biologically-active form only in nestin-positive mesenchymal stem cells conditioned medium and 2 anti-BMP4 antibodies inhibit the nestin-positive mesenchymal

Analysis of epigenetic factors in mouse embryonic neural stem cells exposed to hyperglycemia.

Directory of Open Access Journals (Sweden)

Sukanya Shyamasundar

Full Text Available BACKGROUND: Maternal diabetes alters gene expression leading to neural tube defects (NTDs in the developing brain. The mechanistic pathways that deregulate the gene expression remain unknown. It is hypothesized that exposure of neural stem cells (NSCs to high glucose/hyperglycemia results in activation of epigenetic mechanisms which alter gene expression and cell fate during brain development. METHODS AND FINDINGS: NSCs were isolated from normal pregnancy and streptozotocin induced-diabetic pregnancy and cultured in physiological glucose. In order to examine hyperglycemia induced epigenetic changes in NSCs, chromatin reorganization, global histone status at lysine 9 residue of histone H3 (acetylation and trimethylation and global DNA methylation were examined and found to be altered by hyperglycemia. In NSCs, hyperglycemia increased the expression of Dcx (Doublecortin and Pafah1b1 (Platelet activating factor acetyl hydrolase, isoform 1b, subunit 1 proteins concomitant with decreased expression of four microRNAs (mmu-miR-200a, mmu-miR-200b, mmu-miR-466a-3p and mmu-miR-466 d-3p predicted to target these genes. Knockdown of specific microRNAs in NSCs resulted in increased expression of Dcx and Pafah1b1 proteins confirming target prediction and altered NSC fate by increasing the expression of neuronal and glial lineage markers. CONCLUSION/INTERPRETATION: This study revealed that hyperglycemia alters the epigenetic mechanisms in NSCs, resulting in altered expression of some development control genes which may form the basis for the NTDs. Since epigenetic changes are reversible, they may be valuable therapeutic targets in order to improve fetal outcomes in diabetic pregnancy.

Cell fate determination in the Caenorhabditis elegans epidermal lineages

NARCIS (Netherlands)

Soete, G.A.J.

2007-01-01

The starting point for this work was to use the hypodermal seam of C. elegans as a model system to study cell fate determination. Even though the seam is a relatively simple developmental system, the mechanisms that control cell fate determination in the seam lineages are connected in a highly

Astrocyte glycogen as an emergency fuel under conditions of glucose deprivation or intense neural activity.

Science.gov (United States)

Brown, Angus M; Ransom, Bruce R

2015-02-01

Energy metabolism in the brain is a complex process that is incompletely understood. Although glucose is agreed as the main energy support of the brain, the role of glucose is not clear, which has led to controversies that can be summarized as follows: the fate of glucose, once it enters the brain is unclear. It is not known the form in which glucose enters the cells (neurons and glia) within the brain, nor the degree of metabolic shuttling of glucose derived metabolites between cells, with a key limitation in our knowledge being the extent of oxidative metabolism, and how increased tissue activity alters this. Glycogen is present within the brain and is derived from glucose. Glycogen is stored in astrocytes and acts to provide short-term delivery of substrates to neural elements, although it may also contribute an important component to astrocyte metabolism. The roles played by glycogen awaits further study, but to date its most important role is in supporting neural elements during increased firing activity, where signaling molecules, proposed to be elevated interstitial K(+), indicative of elevated neural firing rates, activate glycogen phosphorylase leading to increased production of glycogen derived substrate.

The fate of accreting white dwarfs: type I supernovae vs. collapse

International Nuclear Information System (INIS)

Nomoto, Ken'ichi

1986-01-01

The fate of accreting white dwarfs is examined with respect to thermonuclear explosion or collapse. The paper was presented to the conference on ''The early universe and its evolution'', Erice, Italy 1986. Effects of accretion and the fate of white dwarfs, models for type 1a and 1b supernovae, collapse induced by carbon deflagration at high density, and fate of double white dwarfs, are all discussed. (U.K.)

Epithelial–Mesenchymal Transitions during Neural Crest and Somite Development

Directory of Open Access Journals (Sweden)

Chaya Kalcheim

2015-12-01

Full Text Available Epithelial-to-mesenchymal transition (EMT is a central process during embryonic development that affects selected progenitor cells of all three germ layers. In addition to driving the onset of cellular migrations and subsequent tissue morphogenesis, the dynamic conversions of epithelium into mesenchyme and vice-versa are intimately associated with the segregation of homogeneous precursors into distinct fates. The neural crest and somites, progenitors of the peripheral nervous system and of skeletal tissues, respectively, beautifully illustrate the significance of EMT to the above processes. Ongoing studies progressively elucidate the gene networks underlying EMT in each system, highlighting the similarities and differences between them. Knowledge of the mechanistic logic of this normal ontogenetic process should provide important insights to the understanding of pathological conditions such as cancer metastasis, which shares some common molecular themes.

Zic-Proteins Are Repressors of Dopaminergic Forebrain Fate in Mice and C. elegans.

Science.gov (United States)

Tiveron, Marie-Catherine; Beclin, Christophe; Murgan, Sabrina; Wild, Stefan; Angelova, Alexandra; Marc, Julie; Coré, Nathalie; de Chevigny, Antoine; Herrera, Eloisa; Bosio, Andreas; Bertrand, Vincent; Cremer, Harold

2017-11-01

In the postnatal forebrain regionalized neural stem cells along the ventricular walls produce olfactory bulb (OB) interneurons with varying neurotransmitter phenotypes and positions. To understand the molecular basis of this region-specific variability we analyzed gene expression in the postnatal dorsal and lateral lineages in mice of both sexes from stem cells to neurons. We show that both lineages maintain transcription factor signatures of their embryonic site of origin, the pallium and subpallium. However, additional factors, including Zic1 and Zic2, are postnatally expressed in the dorsal stem cell compartment and maintained in the lineage that generates calretinin-positive GABAergic neurons for the OB. Functionally, we show that Zic1 and Zic2 induce the generation of calretinin-positive neurons while suppressing dopaminergic fate in the postnatal dorsal lineage. We investigated the evolutionary conservation of the dopaminergic repressor function of Zic proteins and show that it is already present in C. elegans SIGNIFICANCE STATEMENT The vertebrate brain generates thousands of different neuron types. In this work we investigate the molecular mechanisms underlying this variability. Using a genomics approach we identify the transcription factor signatures of defined neural stem cells and neuron populations. Based thereon we show that two related transcription factors, Zic1 and Zic2, are essential to control the balance between two defined neuron types in the postnatal brain. We show that this mechanism is conserved in evolutionary very distant species. Copyright © 2017 the authors 0270-6474/17/3710611-13$15.00/0.

The DIVA model: A neural theory of speech acquisition and production.

Science.gov (United States)

Tourville, Jason A; Guenther, Frank H

2011-01-01

The DIVA model of speech production provides a computationally and neuroanatomically explicit account of the network of brain regions involved in speech acquisition and production. An overview of the model is provided along with descriptions of the computations performed in the different brain regions represented in the model. The latest version of the model, which contains a new right-lateralized feedback control map in ventral premotor cortex, will be described, and experimental results that motivated this new model component will be discussed. Application of the model to the study and treatment of communication disorders will also be briefly described.

Image reconstruction using Monte Carlo simulation and artificial neural networks

International Nuclear Information System (INIS)

Emert, F.; Missimner, J.; Blass, W.; Rodriguez, A.

1997-01-01

PET data sets are subject to two types of distortions during acquisition: the imperfect response of the scanner and attenuation and scattering in the active distribution. In addition, the reconstruction of voxel images from the line projections composing a data set can introduce artifacts. Monte Carlo simulation provides a means for modeling the distortions and artificial neural networks a method for correcting for them as well as minimizing artifacts. (author) figs., tab., refs

Global fate of POPs: Current and future research directions

Energy Technology Data Exchange (ETDEWEB)

Lohmann, Rainer [Graduate School of Oceanography, University of Rhode Island, Narragansett, RI 02882-1197 (United States)], E-mail: lohmann@gso.uri.edu; Breivik, Knut [Norwegian Institute for Air Research, PO Box 100, NO-2027 Kjeller (Norway); University of Oslo, Department of Chemistry, PO Box 1033, NO-0315 Oslo (Norway); Dachs, Jordi [Department of Environmental Chemistry, Institute of Chemical and Environmental Research (IIQAB-CSIC), Jordi Girona 18-26, Barcelona 08034 (Spain); Muir, Derek [Aquatic Ecosystem Protection Research Division, Environment Canada, 867 Lakeshore Road, Burlington, ON L7R4A6 (Canada)

2007-11-15

For legacy and emerging persistent organic pollutants (POPs), surprisingly little is still known in quantitative terms about their global sources and emissions. Atmospheric transport has been identified as the key global dispersal mechanism for most legacy POPs. In contrast, transport by ocean currents may prove to be the main transport route for many polar, emerging POPs. This is linked to the POPs' intrinsic physico-chemical properties, as exemplified by the different fate of hexachlorocyclohexanes in the Arctic. Similarly, our current understanding of POPs' global transport and fate remains sketchy. The importance of organic carbon and global temperature differences have been accepted as key drivers of POPs' global distribution. However, future research will need to understand the various biogeochemical and geophysical cycles under anthropogenic pressures to be able to understand and predict the global fate of POPs accurately. - Future studies into the global fate of POPs will need to pay more attention to the various biogeochemical and anthropogenic cycles to better understand emissions, transport and sinks.

Reactive Oxygen Species and Mitochondrial Homeostasis as Regulators of Stem Cell Fate and Function.

Science.gov (United States)

Tan, Darren Q; Suda, Toshio

2018-07-10

The precise role and impact of reactive oxygen species (ROS) in stem cells, which are essential for lifelong tissue homeostasis and regeneration, remain of significant interest to the field. The long-term regenerative potential of a stem cell compartment is determined by the delicate balance between quiescence, self-renewal, and differentiation, all of which can be influenced by ROS levels. Recent Advances: The past decade has seen a growing appreciation for the importance of ROS and redox homeostasis in various stem cell compartments, particularly those of hematopoietic, neural, and muscle tissues. In recent years, the importance of proteostasis and mitochondria in relation to stem cell biology and redox homeostasis has garnered considerable interest. Here, we explore the reciprocal relationship between ROS and stem cells, with significant emphasis on mitochondria as a core component of redox homeostasis. We discuss how redox signaling, involving cell-fate determining protein kinases and transcription factors, can control stem cell function and fate. We also address the impact of oxidative stress on stem cells, especially oxidative damage of lipids, proteins, and nucleic acids. We further discuss ROS management in stem cells, and present recent evidence supporting the importance of mitochondrial activity and its modulation (via mitochondrial clearance, biogenesis, dynamics, and distribution [i.e., segregation and transfer]) in stem cell redox homeostasis. Therefore, elucidating the intricate links between mitochondria, cellular metabolism, and redox homeostasis is envisioned to be critical for our understanding of ROS in stem cell biology and its therapeutic relevance in regenerative medicine. Antioxid. Redox Signal. 00, 000-000.

Fate of chemical warfare agents and toxic industrial chemicals in landfills.

Science.gov (United States)

Bartelt-Hunt, Shannon L; Barlaz, Morton A; Knappe, Detlef R U; Kjeldsen, Peter

2006-07-01

One component of preparedness for a chemical attack is planning for the disposal of contaminated debris. To assess the feasibility of contaminated debris disposal in municipal solid waste (MSW) landfills, the fate of selected chemical warfare agents (CWAs) and toxic industrial chemicals (TICs) in MSW landfills was predicted with a mathematical model. Five blister agents [sulfur mustard (HD), nitrogen mustard (HN-2), lewisite (L), ethyldichloroarsine (ED), and phosgene oxime (CX)], eight nerve agents [tabun (GA), sarin (GB), soman (GD), GE, GF, VX, VG, and VM], one riot-control agent [CS], and two TICs [furan and carbon disulfide] were studied. The effects of both infiltration (climate) and contaminant biodegradability on fate predictions were assessed. Model results showed that hydrolysis and gas-phase advection were the principal fate pathways for CWAs and TICs, respectively. Apart from CX and the TICs, none of the investigated compounds was predicted to persist in a landfill for more than 5 years. Climate had little impact on CWA/TIC fate, and biodegradability was only important for compounds with long hydrolysis half-lives. Monte Carlo simulations were performed to assess the influence of uncertainty in model input parameters on CWA/TIC fate predictions. Correlation analyses showed that uncertainty in hydrolysis rate constants was the primary contributor to variance of CWA fate predictions, while uncertainty in the Henry's Law constant and landfill gas-production rate accounted for most of the variance of TIC fate predictions. CWA hydrolysates were more persistent than the parent CWAs, but limited information is available on abiotic or biotic transformation rates for these chemicals.

Integrated fate and toxicity assessment for site contaminants

International Nuclear Information System (INIS)

MacDonell, Margaret; Peterson, John; Finster, Molly; Douglas, R.

2007-01-01

Understanding the fate and toxicity of environmental contaminants is essential to framing practical management decisions. Forms and bioavailable concentrations often change over time due to natural physical, chemical, and biological processes. For some sites, hundreds of contaminants may be of initial interest, and even small projects can involve a substantial number of contaminants. With multiple assessments common, attention to effectiveness and efficiency is important, and integrating fate and toxicity information provides a valuable way to focus the analyses. Fate assessments help identify what forms may be present where and when, while toxicity information indicates what health effects could result if people were exposed. The integration process is illustrated by an application for the Hanford site, to support long-term management decisions for the cesium and strontium capsules. Fate data, health-based benchmarks, and related toxicity information were effectively combined to indicate performance targets for chemicals and radionuclides identified for capsule leachate that could migrate to groundwater. More than 50 relevant benchmarks and toxicity context were identified for 15 of the 17 study contaminants; values for chronic drinking water exposure provided the common basis for selected indicators. For two chemicals, toxicity information was identified from the scientific literature to guide the performance targets. (authors)

Fragile x mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells.

Directory of Open Access Journals (Sweden)

Yuping Luo

2010-04-01

Full Text Available Fragile X syndrome (FXS, the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP. FMRP is an RNA-binding protein that can regulate the translation of specific mRNAs. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. In this study, we investigated whether Fmrp deficiency affects adult neurogenesis. We show that in a mouse model of fragile X syndrome, adult neurogenesis is indeed altered. The loss of Fmrp increases the proliferation and alters the fate specification of adult neural progenitor/stem cells (aNPCs. We demonstrate that Fmrp regulates the protein expression of several components critical for aNPC function, including CDK4 and GSK3beta. Dysregulation of GSK3beta led to reduced Wnt signaling pathway activity, which altered the expression of neurogenin1 and the fate specification of aNPCs. These data unveil a novel regulatory role for Fmrp and translational regulation in adult neurogenesis.

Ultimate fate of constrained voters

International Nuclear Information System (INIS)

Vazquez, F; Redner, S

2004-01-01

We examine the ultimate fate of individual opinions in a socially interacting population of leftists, centrists and rightists. In an elemental interaction between agents, a centrist and a leftist can both become centrists or both become leftists with equal rates (and similarly for a centrist and a rightist). However leftists and rightists do not interact. This interaction step between pairs of agents is applied repeatedly until the system can no longer evolve. In the mean-field limit, we determine the exact probability that the system reaches consensus (either leftist, rightist or centrist) or a frozen mixture of leftists and rightists as a function of the initial composition of the population. We also determine the mean time until the final state is reached. Some implications of our results for the ultimate fate in a limit of the Axelrod model are discussed

Ultimate fate of constrained voters

Energy Technology Data Exchange (ETDEWEB)

Vazquez, F [Department of Physics, Center for BioDynamics, Boston University, Boston, MA 02215 (United States); Redner, S [Department of Physics, Center for Polymer Studies, Boston University, Boston, MA 02215 (United States)

2004-09-03

We examine the ultimate fate of individual opinions in a socially interacting population of leftists, centrists and rightists. In an elemental interaction between agents, a centrist and a leftist can both become centrists or both become leftists with equal rates (and similarly for a centrist and a rightist). However leftists and rightists do not interact. This interaction step between pairs of agents is applied repeatedly until the system can no longer evolve. In the mean-field limit, we determine the exact probability that the system reaches consensus (either leftist, rightist or centrist) or a frozen mixture of leftists and rightists as a function of the initial composition of the population. We also determine the mean time until the final state is reached. Some implications of our results for the ultimate fate in a limit of the Axelrod model are discussed.

High-precision position estimation in PET using artificial neural networks

Energy Technology Data Exchange (ETDEWEB)

Mateo, F. [Digital Systems Design Group (DSD), Instituto de las Tecnologias de la Informacion y de las Comunicaciones Avanzadas (ITACA), Universidad Politecnica de Valencia, Camino de Vera s/n, 46022 Valencia (Spain)], E-mail: fermaji@upvnet.upv.es; Aliaga, R.J.; Ferrando, N.; Martinez, J.D.; Herrero, V.; Lerche, Ch.W.; Colom, R.J.; Monzo, J.M.; Sebastia, A.; Gadea, R. [Digital Systems Design Group (DSD), Instituto de las Tecnologias de la Informacion y de las Comunicaciones Avanzadas (ITACA), Universidad Politecnica de Valencia, Camino de Vera s/n, 46022 Valencia (Spain)

2009-06-01

Traditionally, the most popular technique to predict the impact position of gamma photons on a PET detector has been Anger's logic. However, it introduces nonlinearities that compress the light distribution, reducing the useful field of view and the spatial resolution, especially at the edges of the scintillator crystal. In this work, we make use of neural networks to address a bias-corrected position estimation from real stimulus obtained from a 2D PET system setup. The preprocessing and data acquisition were performed by separate custom boards, especially designed for this application. The results show that neural networks yield a more uniform field of view while improving the systematic error and the spatial resolution. Therefore, they stand as a better performing and readily available alternative to classic positioning methods.

High-precision position estimation in PET using artificial neural networks

International Nuclear Information System (INIS)

Mateo, F.; Aliaga, R.J.; Ferrando, N.; Martinez, J.D.; Herrero, V.; Lerche, Ch.W.; Colom, R.J.; Monzo, J.M.; Sebastia, A.; Gadea, R.

2009-01-01

Traditionally, the most popular technique to predict the impact position of gamma photons on a PET detector has been Anger's logic. However, it introduces nonlinearities that compress the light distribution, reducing the useful field of view and the spatial resolution, especially at the edges of the scintillator crystal. In this work, we make use of neural networks to address a bias-corrected position estimation from real stimulus obtained from a 2D PET system setup. The preprocessing and data acquisition were performed by separate custom boards, especially designed for this application. The results show that neural networks yield a more uniform field of view while improving the systematic error and the spatial resolution. Therefore, they stand as a better performing and readily available alternative to classic positioning methods.

Fibronectin promotes differentiation of neural crest progenitors endowed with smooth muscle cell potential

International Nuclear Information System (INIS)

Costa-Silva, Bruno; Coelho da Costa, Meline; Melo, Fernanda Rosene; Neves, Cynara Mendes; Alvarez-Silva, Marcio; Calloni, Giordano Wosgrau; Trentin, Andrea Goncalves

2009-01-01

The neural crest (NC) is a model system used to investigate multipotency during vertebrate development. Environmental factors control NC cell fate decisions. Despite the well-known influence of extracellular matrix molecules in NC cell migration, the issue of whether they also influence NC cell differentiation has not been addressed at the single cell level. By analyzing mass and clonal cultures of mouse cephalic and quail trunk NC cells, we show for the first time that fibronectin (FN) promotes differentiation into the smooth muscle cell phenotype without affecting differentiation into glia, neurons, and melanocytes. Time course analysis indicated that the FN-induced effect was not related to massive cell death or proliferation of smooth muscle cells. Finally, by comparing clonal cultures of quail trunk NC cells grown on FN and collagen type IV (CLIV), we found that FN strongly increased both NC cell survival and the proportion of unipotent and oligopotent NC progenitors endowed with smooth muscle potential. In contrast, melanocytic progenitors were prominent in clonogenic NC cells grown on CLIV. Taken together, these results show that FN promotes NC cell differentiation along the smooth muscle lineage, and therefore plays an important role in fate decisions of NC progenitor cells

Silicon nanowires enhanced proliferation and neuronal differentiation of neural stem cell with vertically surface microenvironment.

Science.gov (United States)

Yan, Qiuting; Fang, Lipao; Wei, Jiyu; Xiao, Guipeng; Lv, Meihong; Ma, Quanhong; Liu, Chunfeng; Wang, Wang

2017-09-01

Owing to its biocompatibility, noncytotoxicity, biodegradability and three-dimensional structure, vertically silicon nanowires (SiNWs) arrays are a promising scaffold material for tissue engineering, regenerative medicine and relevant medical applications. Recently, its osteogenic differentiation effects, reorganization of cytoskeleton and regulation of the fate on stem cells have been demonstrated. However, it still remains unknown whether SiNWs arrays could affect the proliferation and neuronal differentiation of neural stem cells (NSCs) or not. In the present study, we have employed vertically aligned SiNWs arrays as culture systems for NSCs and proved that the scaffold material could promote the proliferation and neuronal differentiation of NSCs while maintaining excellent cell viability and stemness. Immunofluorescence imaging analysis, Western blot and RT-PCR results reveal that NSCs proliferation and neuronal differentiation efficiency on SiNWs arrays are significant greater than that on silicon wafers. These results implicate SiNWs arrays could offer a powerful platform for NSCs research and NSCs-based therapy in the field of neural tissue engineering.

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.

Neural correlates of continuous causal word generation.

Science.gov (United States)

Wende, Kim C; Straube, Benjamin; Stratmann, Mirjam; Sommer, Jens; Kircher, Tilo; Nagels, Arne

2012-09-01

Causality provides a natural structure for organizing our experience and language. Causal reasoning during speech production is a distinct aspect of verbal communication, whose related brain processes are yet unknown. The aim of the current study was to investigate the neural mechanisms underlying the continuous generation of cause-and-effect coherences during overt word production. During fMRI data acquisition participants performed three verbal fluency tasks on identical cue words: A novel causal verbal fluency task (CVF), requiring the production of multiple reasons to a given cue word (e.g. reasons for heat are fire, sun etc.), a semantic (free association, FA, e.g. associations with heat are sweat, shower etc.) and a phonological control task (phonological verbal fluency, PVF, e.g. rhymes with heat are meat, wheat etc.). We found that, in contrast to PVF, both CVF and FA activated a left lateralized network encompassing inferior frontal, inferior parietal and angular regions, with further bilateral activation in middle and inferior as well as superior temporal gyri and the cerebellum. For CVF contrasted against FA, we found greater bold responses only in the left middle frontal cortex. Large overlaps in the neural activations during free association and causal verbal fluency indicate that the access to causal relationships between verbal concepts is at least partly based on the semantic neural network. The selective activation in the left middle frontal cortex for causal verbal fluency suggests that distinct neural processes related to cause-and-effect-relations are associated with the recruitment of middle frontal brain areas. Copyright © 2012 Elsevier Inc. All rights reserved.

Fate of chemical warfare agents and toxic indutrial chemicals in landfills

DEFF Research Database (Denmark)

Bartelt-Hunt, D.L.; Barlaz, M.A.; Knappe, D.R.U.

2006-01-01

One component of preparedness for a chemical attack is planning for the disposal of contaminated debris. To assess the feasibility of contaminated debris disposal in municipal solid waste (MSW) landfills, the fate of selected chemical warfare agents (CWAs) and toxic industrial chemicals (TICs......], and two TICs [furan and carbon disulfide] were studied. The effects of both infiltration (climate) and contaminant biodegradability on fate predictions were assessed. Model results showed that hydrolysis and gas-phase advection were the principal fate pathways for CWAs and TICs, respectively. Apart from...... CX and the TICs, none of the investigated compounds was predicted to persist in a landfill for more than 5 years. Climate had little impact on CWA/TIC fate, and biodegradability was only important for compounds with long hydrolysis halflives. Monte Carlo simulations were performed to assess...

[The tragic fate of physicians].

Science.gov (United States)

Ohry, Avi

2013-10-01

Physicians and surgeons were always involved in revolutions, wars and political activities, as well as in various medical humanities. Tragic fate met these doctors, whether in the Russian prisons gulags, German labor or concentration camps, pogroms or at the hands of the Inquisition.

Acquisition of multiple prior distributions in tactile temporal order judgment

Directory of Open Access Journals (Sweden)

Yasuhito eNagai

2012-08-01

Full Text Available The Bayesian estimation theory proposes that the brain acquires the prior distribution of a task and integrates it with sensory signals to minimize the effect of sensory noise. Psychophysical studies have demonstrated that our brain actually implements Bayesian estimation in a variety of sensory-motor tasks. However, these studies only imposed one prior distribution on participants within a task period. In this study, we investigated the conditions that enable the acquisition of multiple prior distributions in temporal order judgment (TOJ of two tactile stimuli across the hands. In Experiment 1, stimulation intervals were randomly selected from one of two prior distributions (biased to right hand earlier and biased to left hand earlier in association with color cues (green and red, respectively. Although the acquisition of the two priors was not enabled by the color cues alone, it was significant when participants shifted their gaze (above or below in response to the color cues. However, the acquisition of multiple priors was not significant when participants moved their mouths (opened or closed. In Experiment 2, the spatial cues (above and below were used to identify which eye position or retinal cue position was crucial for the eye-movement-dependent acquisition of multiple priors in Experiment 1. The acquisition of the two priors was significant when participants moved their gaze to the cues (i.e., the cue positions on the retina were constant across the priors, as well as when participants did not shift their gazes (i.e., the cue positions on the retina changed according to the priors. Thus, both eye and retinal cue positions were effective in acquiring multiple priors. Based on previous neurophysiological reports, we discuss possible neural correlates that contribute to the acquisition of multiple priors.

Development of test algorithm for semiconductor package with defects by using probabilistic neural network

International Nuclear Information System (INIS)

Kim, Jae Yeol; Sim, Jae Gi; Ko, Myoung Soo; Kim, Chang Hyun; Kim, Hun Cho

2001-01-01

In this study, researchers developing the estimative algorithm for artificial defects in semiconductor packages and performing it by pattern recognition technology. For this purpose, the estimative algorithm was included that researchers made software with MATLAB. The software consists of some procedures including ultrasonic image acquisition, equalization filtering, Self-Organizing Map and Probabilistic Neural Network. Self-Organizing Map and Probabilistic Neural Network are belong to methods of Neural Networks. And the pattern recognition technology has applied to classify three kinds of detective patterns in semiconductor packages. This study presumes probability density function from a sample of learning and present which is automatically determine method. PNN can distinguish flaws very difficult distinction as well as. This can do parallel process to stand in a row we confirm that is very efficiently classifier if we applied many data real the process.

A polynomial based model for cell fate prediction in human diseases.

Science.gov (United States)

Ma, Lichun; Zheng, Jie

2017-12-21

Cell fate regulation directly affects tissue homeostasis and human health. Research on cell fate decision sheds light on key regulators, facilitates understanding the mechanisms, and suggests novel strategies to treat human diseases that are related to abnormal cell development. In this study, we proposed a polynomial based model to predict cell fate. This model was derived from Taylor series. As a case study, gene expression data of pancreatic cells were adopted to test and verify the model. As numerous features (genes) are available, we employed two kinds of feature selection methods, i.e. correlation based and apoptosis pathway based. Then polynomials of different degrees were used to refine the cell fate prediction function. 10-fold cross-validation was carried out to evaluate the performance of our model. In addition, we analyzed the stability of the resultant cell fate prediction model by evaluating the ranges of the parameters, as well as assessing the variances of the predicted values at randomly selected points. Results show that, within both the two considered gene selection methods, the prediction accuracies of polynomials of different degrees show little differences. Interestingly, the linear polynomial (degree 1 polynomial) is more stable than others. When comparing the linear polynomials based on the two gene selection methods, it shows that although the accuracy of the linear polynomial that uses correlation analysis outcomes is a little higher (achieves 86.62%), the one within genes of the apoptosis pathway is much more stable. Considering both the prediction accuracy and the stability of polynomial models of different degrees, the linear model is a preferred choice for cell fate prediction with gene expression data of pancreatic cells. The presented cell fate prediction model can be extended to other cells, which may be important for basic research as well as clinical study of cell development related diseases.

Prostaglandin E2 Regulates Liver versus Pancreas Cell Fate Decisions and Endodermal Outgrowth

Science.gov (United States)

Nissim, Sahar; Sherwood, Richard I.; Wucherpfennig, Julia; Saunders, Diane; Harris, James M.; Esain, Virginie; Carroll, Kelli J.; Frechette, Gregory M.; Kim, Andrew J.; Hwang, Katie L.; Cutting, Claire C.; Elledge, Susanna; North, Trista E.; Goessling, Wolfram

2014-01-01

SUMMARY The liver and pancreas arise from common endodermal progenitors. How these distinct cell fates are specified is poorly understood. Here, we describe prostaglandin E2 (PGE2) as a regulator of endodermal fate specification during development. Modulating PGE2 activity has opposing effects on liver-versus-pancreas specification in zebrafish embryos as well as mouse endodermal progenitors. The PGE2 synthetic enzyme cox2a and receptor ep2a are patterned such that cells closest to PGE2 synthesis acquire a liver fate whereas more distant cells acquire a pancreas fate. PGE2 interacts with the bmp2b pathway to regulate fate specification. At later stages of development, PGE2 acting via the ep4a receptor promotes outgrowth of both the liver and pancreas. PGE2 remains important for adult organ growth, as it modulates liver regeneration. This work provides in vivo evidence that PGE2 may act as a morphogen to regulate cell fate decisions and outgrowth of the embryonic endodermal anlagen. PMID:24530296

Direct imaging of neural currents using ultra-low field magnetic resonance techniques

Science.gov (United States)

Volegov, Petr L [Los Alamos, NM; Matlashov, Andrei N [Los Alamos, NM; Mosher, John C [Los Alamos, NM; Espy, Michelle A [Los Alamos, NM; Kraus, Jr., Robert H.

2009-08-11

Using resonant interactions to directly and tomographically image neural activity in the human brain using magnetic resonance imaging (MRI) techniques at ultra-low field (ULF), the present inventors have established an approach that is sensitive to magnetic field distributions local to the spin population in cortex at the Larmor frequency of the measurement field. Because the Larmor frequency can be readily manipulated (through varying B.sub.m), one can also envision using ULF-DNI to image the frequency distribution of the local fields in cortex. Such information, taken together with simultaneous acquisition of MEG and ULF-NMR signals, enables non-invasive exploration of the correlation between local fields induced by neural activity in cortex and more `distant` measures of brain activity such as MEG and EEG.

Regulatory Role of Redox Balance in Determination of Neural Precursor Cell Fate

Directory of Open Access Journals (Sweden)

Mohamed Ariff Iqbal

2017-01-01

Full Text Available In 1990s, reports of discovery of a small group of cells capable of proliferation and contribution to formation of new neurons in the central nervous system (CNS reversed a century-old concept on lack of neurogenesis in the adult mammalian brain. These cells are found in all stages of human life and contribute to normal cellular turnover of the CNS. Therefore, the identity of regulating factors that affect their proliferation and differentiation is a highly noteworthy issue for basic scientists and their clinician counterparts for therapeutic purposes. The cues for such control are embedded in developmental and environmental signaling through a highly regulated tempo-spatial expression of specific transcription factors. Novel findings indicate the importance of reactive oxygen species (ROS in the regulation of this signaling system. The elusive nature of ROS signaling in many vital processes from cell proliferation to cell death creates a complex literature in this field. Here, we discuss the emerging thoughts on the importance of redox regulation of proliferation and maintenance in mammalian neural stem and progenitor cells under physiological and pathological conditions. The current knowledge on ROS-mediated changes in redox-sensitive proteins that govern the molecular mechanisms in proliferation and differentiation of these cells is reviewed.

BTG interacts with retinoblastoma to control cell fate in Dictyostelium.

Directory of Open Access Journals (Sweden)

Daniele Conte

Full Text Available BACKGROUND: In the genesis of many tissues, a phase of cell proliferation is followed by cell cycle exit and terminal differentiation. The latter two processes overlap: genes involved in the cessation of growth may also be important in triggering differentiation. Though conceptually distinct, they are often causally related and functional interactions between the cell cycle machinery and cell fate control networks are fundamental to coordinate growth and differentiation. A switch from proliferation to differentiation may also be important in the life cycle of single-celled organisms, and genes which arose as regulators of microbial differentiation may be conserved in higher organisms. Studies in microorganisms may thus contribute to understanding the molecular links between cell cycle machinery and the determination of cell fate choice networks. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that in the amoebozoan D. discoideum, an ortholog of the metazoan antiproliferative gene btg controls cell fate, and that this function is dependent on the presence of a second tumor suppressor ortholog, the retinoblastoma-like gene product. Specifically, we find that btg-overexpressing cells preferentially adopt a stalk cell (and, more particularly, an Anterior-Like Cell fate. No btg-dependent preference for ALC fate is observed in cells in which the retinoblastoma-like gene has been genetically inactivated. Dictyostelium btg is the only example of non-metazoan member of the BTG family characterized so far, suggesting that a genetic interaction between btg and Rb predated the divergence between dictyostelids and metazoa. CONCLUSIONS/SIGNIFICANCE: While the requirement for retinoblastoma function for BTG antiproliferative activity in metazoans is known, an interaction of these genes in the control of cell fate has not been previously documented. Involvement of a single pathway in the control of mutually exclusive processes may have relevant implication in the

Neural Correlates of Morphology Acquisition through a Statistical Learning Paradigm.

Science.gov (United States)

Sandoval, Michelle; Patterson, Dianne; Dai, Huanping; Vance, Christopher J; Plante, Elena

2017-01-01

The neural basis of statistical learning as it occurs over time was explored with stimuli drawn from a natural language (Russian nouns). The input reflected the "rules" for marking categories of gendered nouns, without making participants explicitly aware of the nature of what they were to learn. Participants were scanned while listening to a series of gender-marked nouns during four sequential scans, and were tested for their learning immediately after each scan. Although participants were not told the nature of the learning task, they exhibited learning after their initial exposure to the stimuli. Independent component analysis of the brain data revealed five task-related sub-networks. Unlike prior statistical learning studies of word segmentation, this morphological learning task robustly activated the inferior frontal gyrus during the learning period. This region was represented in multiple independent components, suggesting it functions as a network hub for this type of learning. Moreover, the results suggest that subnetworks activated by statistical learning are driven by the nature of the input, rather than reflecting a general statistical learning system.

Self-organizing map models of language acquisition

Science.gov (United States)

Li, Ping; Zhao, Xiaowei

2013-01-01

Connectionist models have had a profound impact on theories of language. While most early models were inspired by the classic parallel distributed processing architecture, recent models of language have explored various other types of models, including self-organizing models for language acquisition. In this paper, we aim at providing a review of the latter type of models, and highlight a number of simulation experiments that we have conducted based on these models. We show that self-organizing connectionist models can provide significant insights into long-standing debates in both monolingual and bilingual language development. We suggest future directions in which these models can be extended, to better connect with behavioral and neural data, and to make clear predictions in testing relevant psycholinguistic theories. PMID:24312061

Sall1 regulates cortical neurogenesis and laminar fate specification in mice: implications for neural abnormalities in Townes-Brocks syndrome

Directory of Open Access Journals (Sweden)

Susan J. Harrison

2012-05-01

Progenitor cells in the cerebral cortex undergo dynamic cellular and molecular changes during development. Sall1 is a putative transcription factor that is highly expressed in progenitor cells during development. In humans, the autosomal dominant developmental disorder Townes-Brocks syndrome (TBS is associated with mutations of the SALL1 gene. TBS is characterized by renal, anal, limb and auditory abnormalities. Although neural deficits have not been recognized as a diagnostic characteristic of the disease, ∼10% of patients exhibit neural or behavioral abnormalities. We demonstrate that, in addition to being expressed in peripheral organs, Sall1 is robustly expressed in progenitor cells of the central nervous system in mice. Both classical- and conditional-knockout mouse studies indicate that the cerebral cortex is particularly sensitive to loss of Sall1. In the absence of Sall1, both the surface area and depth of the cerebral cortex were decreased at embryonic day 18.5 (E18.5. These deficiencies are associated with changes in progenitor cell properties during development. In early cortical progenitor cells, Sall1 promotes proliferative over neurogenic division, whereas, at later developmental stages, Sall1 regulates the production and differentiation of intermediate progenitor cells. Furthermore, Sall1 influences the temporal specification of cortical laminae. These findings present novel insights into the function of Sall1 in the developing mouse cortex and provide avenues for future research into potential neural deficits in individuals with TBS.

Chemo-mechanical control of neural stem cell differentiation

Science.gov (United States)

Geishecker, Emily R.

Cellular processes such as adhesion, proliferation, and differentiation are controlled in part by cell interactions with the microenvironment. Cells can sense and respond to a variety of stimuli, including soluble and insoluble factors (such as proteins and small molecules) and externally applied mechanical stresses. Mechanical properties of the environment, such as substrate stiffness, have also been suggested to play an important role in cell processes. The roles of both biochemical and mechanical signaling in fate modification of stem cells have been explored independently. However, very few studies have been performed to study well-controlled chemo-mechanotransduction. The objective of this work is to design, synthesize, and characterize a chemo-mechanical substrate to encourage neuronal differentiation of C17.2 neural stem cells. In Chapter 2, Polyacrylamide (PA) gels of varying stiffnesses are functionalized with differing amounts of whole collagen to investigate the role of protein concentration in combination with substrate stiffness. As expected, neurons on the softest substrate were more in number and neuronal morphology than those on stiffer substrates. Neurons appeared locally aligned with an expansive network of neurites. Additional experiments would allow for statistical analysis to determine if and how collagen density impacts C17.2 differentiation in combination with substrate stiffness. Due to difficulties associated with whole protein approaches, a similar platform was developed using mixed adhesive peptides, derived from fibronectin and laminin, and is presented in Chapter 3. The matrix elasticity and peptide concentration can be individually modulated to systematically probe the effects of chemo-mechanical signaling on differentiation of C17.2 cells. Polyacrylamide gel stiffness was confirmed using rheological techniques and found to support values published by Yeung et al. [1]. Cellular growth and differentiation were assessed by cell counts

Cyclin D2 in the basal process of neural progenitors is linked to non-equivalent cell fates

Science.gov (United States)

Tsunekawa, Yuji; Britto, Joanne M; Takahashi, Masanori; Polleux, Franck; Tan, Seong-Seng; Osumi, Noriko

2012-01-01

Asymmetric cell division plays an indispensable role during corticogenesis for producing new neurons while maintaining a self-renewing pool of apical progenitors. The cellular and molecular determinants favouring asymmetric division are not completely understood. Here, we identify a novel mechanism for generating cellular asymmetry through the active transportation and local translation of Cyclin D2 mRNA in the basal process. This process is regulated by a unique cis-regulatory sequence found in the 3′ untranslated region (3′UTR) of the mRNA. Unequal inheritance of Cyclin D2 protein to the basally positioned daughter cell with the basal process confers renewal of the apical progenitor after asymmetric division. Conversely, depletion of Cyclin D2 in the apically positioned daughter cell results in terminal neuronal differentiation. We demonstrate that Cyclin D2 is also expressed in the developing human cortex within similar domains, thus indicating that its role as a fate determinant is ancient and conserved. PMID:22395070

Neurog1 Genetic Inducible Fate Mapping (GIFM) Reveals the Existence of Complex Spatiotemporal Cyto-Architectures in the Developing Cerebellum.

Science.gov (United States)

Obana, Edwin A; Lundell, Travis G; Yi, Kevin J; Radomski, Kryslaine L; Zhou, Qiong; Doughty, Martin L

2015-06-01

Neurog1 is a pro-neural basic helix-loop-helix (bHLH) transcription factor expressed in progenitor cells located in the ventricular zone and subsequently the presumptive white matter tracts of the developing mouse cerebellum. We used genetic inducible fate mapping (GIFM) with a transgenic Neurog1-CreER allele to characterize the contributions of Neurog1 lineages to cerebellar circuit formation in mice. GIFM reveals Neurog1-expressing progenitors are fate-mapped to become Purkinje cells and all GABAergic interneuron cell types of the cerebellar cortex but not glia. The spatiotemporal sequence of GIFM is unique to each neuronal cell type. GIFM on embryonic days (E) 10.5 to E12.5 labels Purkinje cells with different medial-lateral settling patterns depending on the day of tamoxifen delivery. GIFM on E11.5 to P7 labels interneurons and the timing of tamoxifen administration correlates with the final inside-to-outside resting position of GABAergic interneurons in the cerebellar cortex. Proliferative status and long-term BrdU retention of GIFM lineages reveals Purkinje cells express Neurog1 around the time they become post-mitotic. In contrast, GIFM labels mitotic and post-mitotic interneurons. Neurog1-CreER GIFM reveals a correlation between the timing of Neurog1 expression and the spatial organization of GABAergic neurons in the cerebellar cortex with possible implications for cerebellar circuit assembly.

Developmental fate and lineage commitment of singled mouse blastomeres.

Science.gov (United States)

Lorthongpanich, Chanchao; Doris, Tham Puay Yoke; Limviphuvadh, Vachiranee; Knowles, Barbara B; Solter, Davor

2012-10-01

The inside-outside model has been invoked to explain cell-fate specification of the pre-implantation mammalian embryo. Here, we investigate whether cell-cell interaction can influence the fate specification of embryonic blastomeres by sequentially separating the blastomeres in two-cell stage mouse embryos and continuing separation after each cell division throughout pre-implantation development. This procedure eliminates information provided by cell-cell interaction and cell positioning. Gene expression profiles, polarity protein localization and functional tests of these separated blastomeres reveal that cell interactions, through cell position, influence the fate of the blastomere. Blastomeres, in the absence of cell contact and inner-outer positional information, have a unique pattern of gene expression that is characteristic of neither inner cell mass nor trophectoderm, but overall they have a tendency towards a 'trophectoderm-like' gene expression pattern and preferentially contribute to the trophectoderm lineage.

Human population intake fractions and environmental fate factors of toxic pollutants in life cycle impact assessment

NARCIS (Netherlands)

Huijbregts, M.A.J.; Struijs, Jaap; Goedkoop, Mark; Heijungs, Reinout; Jan Hendriks, A.; Van De Meent, Dik

2005-01-01

The present paper outlines an update of the fate and exposure part of the fate, exposure and effects model USES-LCA. The new fate and exposure module of USES-LCA was applied to calculate human population intake fractions and fate factors of the freshwater, marine and terrestrial environment for 3393

Fate of nano- and microplastic in freshwater systems: A modeling study

NARCIS (Netherlands)

Besseling, Ellen; Quik, Joris T.K.; Sun, Muzhi; Koelmans, Bart

2017-01-01

Riverine transport to the marine environment is an important pathway for microplastic. However, information on fate and transport of nano- and microplastic in freshwater systems is lacking. Here we present scenario studies on the fate and transport of nano-to millimetre sized spherical particles

Redundant mechanisms are involved in suppression of default cell fates during embryonic mesenchyme and notochord induction in ascidians.

Science.gov (United States)

Kodama, Hitoshi; Miyata, Yoshimasa; Kuwajima, Mami; Izuchi, Ryoichi; Kobayashi, Ayumi; Gyoja, Fuki; Onuma, Takeshi A; Kumano, Gaku; Nishida, Hiroki

2016-08-01

During embryonic induction, the responding cells invoke an induced developmental program, whereas in the absence of an inducing signal, they assume a default uninduced cell fate. Suppression of the default fate during the inductive event is crucial for choice of the binary cell fate. In contrast to the mechanisms that promote an induced cell fate, those that suppress the default fate have been overlooked. Upon induction, intracellular signal transduction results in activation of genes encoding key transcription factors for induced tissue differentiation. It is elusive whether an induced key transcription factor has dual functions involving suppression of the default fates and promotion of the induced fate, or whether suppression of the default fate is independently regulated by other factors that are also downstream of the signaling cascade. We show that during ascidian embryonic induction, default fates were suppressed by multifold redundant mechanisms. The key transcription factor, Twist-related.a, which is required for mesenchyme differentiation, and another independent transcription factor, Lhx3, which is dispensable for mesenchyme differentiation, sequentially and redundantly suppress the default muscle fate in induced mesenchyme cells. Similarly in notochord induction, Brachyury, which is required for notochord differentiation, and other factors, Lhx3 and Mnx, are likely to suppress the default nerve cord fate redundantly. Lhx3 commonly suppresses the default fates in two kinds of induction. Mis-activation of the autonomously executed default program in induced cells is detrimental to choice of the binary cell fate. Multifold redundant mechanisms would be required for suppression of the default fate to be secure. Copyright © 2016 Elsevier Inc. All rights reserved.

Pollutant transport and fate in ecosystems

International Nuclear Information System (INIS)

Coughtrey, P.J.; Martin, M.H.; Unsworth, M.H.

1987-01-01

This publication contains a selection of the papers that were presented at a meeting of the Industrial Ecology Group of the British Ecological Society, held at the University of Bristol 1-4 April 1985. The aim of the meeting was to discuss the processes and mechanisms underlying the transfer of pollutants and contaminants in ecological systems. The discussion of the impact of pollutants on individual organisms, populations and communities was specifically excluded. Parallels between transfer, distribution and fate of a wide range of materials were identified. The papers presented at the meeting provided examples of mechanisms and processes involved in pollutant transport through ecosystems as well as of the significance of long-term or widespread investigations in the identification of temporal or geographical trends. Examples were also provided of studies involving complex systems and diverse materials with the aim of identifying underlying principles. Topics of current environmental concern e.g. acid deposition, heavy metals, radioactivity, etc. for which information is being collated in order to provide a basis for assessments concerning future impact were presented. Such assessments will require a combination of the information on transport and fate within ecosystems with knowledge of the effects of pollutants on the system. The interpretation of data concerning effects of a pollutant needs to be placed in the wider context of the occurrence, distribution and fate of that pollutant. The purpose of this publication is to provide that wider context. (author)

Fate modelling of chemical compounds with incomplete data sets

DEFF Research Database (Denmark)

Birkved, Morten; Heijungs, Reinout

2011-01-01

Impact assessment of chemical compounds in Life Cycle Impact Assessment (LCIA) and Environmental Risk Assessment (ERA) requires a vast amount of data on the properties of the chemical compounds being assessed. These data are used in multi-media fate and exposure models, to calculate risk levels...... in an approximate way. The idea is that not all data needed in a multi-media fate and exposure model are completely independent and equally important, but that there are physical-chemical and biological relationships between sets of chemical properties. A statistical model is constructed to underpin this assumption...... and other indicators. ERA typically addresses one specific chemical, but in an LCIA, the number of chemicals encountered may be quite high, up to hundreds or thousands. This study explores the development of meta-models, which are supposed to reflect the “true”multi-media fate and exposure model...

Progressive Recruitment of Mesenchymal Progenitors Reveals a Time-Dependent Process of Cell Fate Acquisition in Mouse and Human Nephrogenesis.

Science.gov (United States)

Lindström, Nils O; De Sena Brandine, Guilherme; Tran, Tracy; Ransick, Andrew; Suh, Gio; Guo, Jinjin; Kim, Albert D; Parvez, Riana K; Ruffins, Seth W; Rutledge, Elisabeth A; Thornton, Matthew E; Grubbs, Brendan; McMahon, Jill A; Smith, Andrew D; McMahon, Andrew P

2018-06-04

Mammalian nephrons arise from a limited nephron progenitor pool through a reiterative inductive process extending over days (mouse) or weeks (human) of kidney development. Here, we present evidence that human nephron patterning reflects a time-dependent process of recruitment of mesenchymal progenitors into an epithelial nephron precursor. Progressive recruitment predicted from high-resolution image analysis and three-dimensional reconstruction of human nephrogenesis was confirmed through direct visualization and cell fate analysis of mouse kidney organ cultures. Single-cell RNA sequencing of the human nephrogenic niche provided molecular insights into these early patterning processes and predicted developmental trajectories adopted by nephron progenitor cells in forming segment-specific domains of the human nephron. The temporal-recruitment model for nephron polarity and patterning suggested by direct analysis of human kidney development provides a framework for integrating signaling pathways driving mammalian nephrogenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

Fate of Gases generated from Nuclear Wastes

Energy Technology Data Exchange (ETDEWEB)

Srinivasulu, M.; Francis, A. J. [Pohang Univ. of Science and Technology, Pohang (Korea, Republic of); Francis, A. J. [Brookhaven National Laboratory, New York (United States)

2013-05-15

The backfill materials such as cement, bentonite or crushed rock are used as engineered barriers against groundwater infiltration and radionuclide transport. Gas generation from radioactive wastes is attributed to radiolysis, corrosion of metals, and degradation of organic materials. Corrosion of steel drums and biodegradation of organic materials in L/ILW can generate gas which causes pressure build up and has the potential to compromise the integrity of waste containers and release the radionuclides and other contaminants into the environment. Performance assessment therefore requires a detailed understanding of the source and fate of gas generation and transport within the disposal system. Here we review the sources and fate of various type of gases generated from nuclear wastes and repositories. Studies on modeling of the fate and transport of repository gases primarily deal with hydrogen and CO{sub 2}. Although hydrogen and carbon dioxide are the major gases of concern, microbial transformations of these gases in the subterranean environments could be significant. Metabolism of hydrogen along with the carbon dioxide results in the formation of methane, low molecular weight organic compounds and cell biomass and thus could affect the total inventory in a repository environment. Modeling studies should take into consideration of both the gas generation and consumption processes over the long-term.

Radionuclide fate and effects

International Nuclear Information System (INIS)

Anon.

1983-01-01

The studies reported here deal with the full range of contaminant behavior and fate, from the initial physicochemical factors that govern radionuclide availability in terrestrial and aquatic environments to studies of contaminant transport by biological means. By design, we focus more on the biologically and chemically mediated transport processes and food-chain pathways than on the purely physical forms of contaminant transport, such as transport by wind and water

The Specification of Cortical Subcerebral Projection Neurons Depends on the Direct Repression of TBR1 by CTIP1/BCL11a.

Science.gov (United States)

Cánovas, José; Berndt, F Andrés; Sepúlveda, Hugo; Aguilar, Rodrigo; Veloso, Felipe A; Montecino, Martín; Oliva, Carlos; Maass, Juan C; Sierralta, Jimena; Kukuljan, Manuel

2015-05-13

The acquisition of distinct neuronal fates is fundamental for the function of the cerebral cortex. We find that the development of subcerebral projections from layer 5 neurons in the mouse neocortex depends on the high levels of expression of the transcription factor CTIP1; CTIP1 is coexpressed with CTIP2 in neurons that project to subcerebral targets and with SATB2 in those that project to the contralateral cortex. CTIP1 directly represses Tbr1 in layer 5, which appears as a critical step for the acquisition of the subcerebral fate. In contrast, lower levels of CTIP1 in layer 6 are required for TBR1 expression, which directs the corticothalamic fate. CTIP1 does not appear to play a critical role in the acquisition of the callosal projection fate in layer 5. These findings unravel a key step in the acquisition of cell fate for closely related corticofugal neurons and indicate that differential dosages of transcriptions factors are critical to specify different neuronal identities. Copyright © 2015 the authors 0270-6474/15/357552-13$15.00/0.

Three neural network based sensor systems for environmental monitoring

International Nuclear Information System (INIS)

Keller, P.E.; Kouzes, R.T.; Kangas, L.J.

1994-05-01

Compact, portable systems capable of quickly identifying contaminants in the field are of great importance when monitoring the environment. One of the missions of the Pacific Northwest Laboratory is to examine and develop new technologies for environmental restoration and waste management at the Hanford Site. In this paper, three prototype sensing systems are discussed. These prototypes are composed of sensing elements, data acquisition system, computer, and neural network implemented in software, and are capable of automatically identifying contaminants. The first system employs an array of tin-oxide gas sensors and is used to identify chemical vapors. The second system employs an array of optical sensors and is used to identify the composition of chemical dyes in liquids. The third system contains a portable gamma-ray spectrometer and is used to identify radioactive isotopes. In these systems, the neural network is used to identify the composition of the sensed contaminant. With a neural network, the intense computation takes place during the training process. Once the network is trained, operation consists of propagating the data through the network. Since the computation involved during operation consists of vector-matrix multiplication and application of look-up tables unknown samples can be rapidly identified in the field

Learning to Produce Syllabic Speech Sounds via Reward-Modulated Neural Plasticity

Science.gov (United States)

Warlaumont, Anne S.; Finnegan, Megan K.

2016-01-01

At around 7 months of age, human infants begin to reliably produce well-formed syllables containing both consonants and vowels, a behavior called canonical babbling. Over subsequent months, the frequency of canonical babbling continues to increase. How the infant’s nervous system supports the acquisition of this ability is unknown. Here we present a computational model that combines a spiking neural network, reinforcement-modulated spike-timing-dependent plasticity, and a human-like vocal tract to simulate the acquisition of canonical babbling. Like human infants, the model’s frequency of canonical babbling gradually increases. The model is rewarded when it produces a sound that is more auditorily salient than sounds it has previously produced. This is consistent with data from human infants indicating that contingent adult responses shape infant behavior and with data from deaf and tracheostomized infants indicating that hearing, including hearing one’s own vocalizations, is critical for canonical babbling development. Reward receipt increases the level of dopamine in the neural network. The neural network contains a reservoir with recurrent connections and two motor neuron groups, one agonist and one antagonist, which control the masseter and orbicularis oris muscles, promoting or inhibiting mouth closure. The model learns to increase the number of salient, syllabic sounds it produces by adjusting the base level of muscle activation and increasing their range of activity. Our results support the possibility that through dopamine-modulated spike-timing-dependent plasticity, the motor cortex learns to harness its natural oscillations in activity in order to produce syllabic sounds. It thus suggests that learning to produce rhythmic mouth movements for speech production may be supported by general cortical learning mechanisms. The model makes several testable predictions and has implications for our understanding not only of how syllabic vocalizations develop

Characterizing fate and transport properties in karst aquifers under different hydrologic conditions

Science.gov (United States)

Rodriguez, E.; Padilla, I. Y.

2017-12-01

Karst landscapes contain very productive aquifers. The hydraulic and hydrogeological characteristics of karst aquifers make these systems capable of storing and transporting large amount of water, but also highly vulnerable to contamination. Their extremely heterogeneous nature prevents accurate prediction in contaminant fate and transport. Even more challenging is to understand the impact of hydrologic conditions changes on fate and transport processes. This studies aims at characterizing fate and transport processes in the karst groundwater system of northern Puerto Rico under different hydrologic conditions. The study involves injecting rhodamine and uranine dyes into a sinkhole, and monitoring concentrations at a spring. Results show incomplete recovery of tracers, but breaking curves can be used to estimate advective, dispersive and mass transfer characteristic of the karst system. Preliminary results suggest significant differences in fate and transport characteristics under different hydrologic conditions.

Interconnected growing self-organizing maps for auditory and semantic acquisition modeling

Directory of Open Access Journals (Sweden)

Mengxue eCao

2014-03-01

Full Text Available Based on the incremental nature of knowledge acquisition, in this study we propose a growing self-organizing neural network approach for modeling the acquisition of auditory and semantic categories. We introduce an Interconnected Growing Self-Organizing Maps (I-GSOM algorithm, which takes associations between auditory information and semantic information into consideration, in this paper. Direct phonetic--semantic association is simulated in order to model the language acquisition in early phases, such as the babbling and imitation stages, in which no phonological representations exist. Based on the I-GSOM algorithm, we conducted experiments using paired acoustic and semantic training data. We use a cyclical reinforcing and reviewing training procedure to model the teaching and learning process between children and their communication partners; a reinforcing-by-link training procedure and a link-forgetting procedure are introduced to model the acquisition of associative relations between auditory and semantic information. Experimental results indicate that (1 I-GSOM has good ability to learn auditory and semantic categories presented within the training data; (2 clear auditory and semantic boundaries can be found in the network representation; (3 cyclical reinforcing and reviewing training leads to a detailed categorization as well as to a detailed clustering, while keeping the clusters that have already been learned and the network structure that has already been developed stable; and (4 reinforcing-by-link training leads to well-perceived auditory--semantic associations. Our I-GSOM model suggests that it is important to associate auditory information with semantic information during language acquisition. Despite its high level of abstraction, our I-GSOM approach can be interpreted as a biologically-inspired neurocomputational model.

Regulatory relevant and reliable methods and data for determining the environmental fate of manufactured nanomaterials

DEFF Research Database (Denmark)

Baun, Anders; Sayre, Phil; Steinhäuser, Klaus Günter

2017-01-01

The widespread use of manufactured nanomaterials (MN) increases the need for describing and predicting their environmental fate and behaviour. A number of recent reviews have addressed the scientific challenges in disclosing the governing processes for the environmental fate and behaviour of MNs,...... data. Gaps do however exist in test methods for environmental fate, such as methods to estimate heteroagglomeration and the tendency for MNs to transform in the environment.......The widespread use of manufactured nanomaterials (MN) increases the need for describing and predicting their environmental fate and behaviour. A number of recent reviews have addressed the scientific challenges in disclosing the governing processes for the environmental fate and behaviour of MNs......, however there has been less focus on the regulatory adequacy of the data available for MN. The aim of this paper is therefore to review data, testing protocols and guidance papers which describe the environmental fate and behaviour of MN with a focus on their regulatory reliability and relevance. Given...

Neural circuitry of abdominal pain-related fear learning and reinstatement in irritable bowel syndrome.

Science.gov (United States)

Icenhour, A; Langhorst, J; Benson, S; Schlamann, M; Hampel, S; Engler, H; Forsting, M; Elsenbruch, S

2015-01-01

Altered pain anticipation likely contributes to disturbed central pain processing in chronic pain conditions like irritable bowel syndrome (IBS), but the learning processes shaping the expectation of pain remain poorly understood. We assessed the neural circuitry mediating the formation, extinction, and reactivation of abdominal pain-related memories in IBS patients compared to healthy controls (HC) in a differential fear conditioning paradigm. During fear acquisition, predictive visual cues (CS(+)) were paired with rectal distensions (US), while control cues (CS(-)) were presented unpaired. During extinction, only CSs were presented. Subsequently, memory reactivation was assessed with a reinstatement procedure involving unexpected USs. Using functional magnetic resonance imaging, group differences in neural activation to CS(+) vs CS(-) were analyzed, along with skin conductance responses (SCR), CS valence, CS-US contingency, state anxiety, salivary cortisol, and alpha-amylase activity. The contribution of anxiety symptoms was addressed in covariance analyses. Fear acquisition was altered in IBS, as indicated by more accurate contingency awareness, greater CS-related valence change, and enhanced CS(+)-induced differential activation of prefrontal cortex and amygdala. IBS patients further revealed enhanced differential cingulate activation during extinction and greater differential hippocampal activation during reinstatement. Anxiety affected neural responses during memory formation and reinstatement. Abdominal pain-related fear learning and memory processes are altered in IBS, mediated by amygdala, cingulate cortex, prefrontal areas, and hippocampus. Enhanced reinstatement may contribute to hypervigilance and central pain amplification, especially in anxious patients. Preventing a 'relapse' of learned fear utilizing extinction-based interventions may be a promising treatment goal in IBS. © 2014 John Wiley & Sons Ltd.

Fate of acetone in water

Science.gov (United States)

Rathbun, R.E.; Stephens, D.W.; Shultz, D.J.

1982-01-01

The physical, chemical, and biological processes that might affect the concentration of acetone in water were investigated in laboratory studies. Processes considered included volatilization, adsorption by sediments, photodecomposition, bacterial degradation, and absorption by algae and molds. It was concluded that volatilization and bacterial degradation were the dominant processes determining the fate of acetone in streams and rivers. ?? 1982.

The transcription factor Nerfin-1 prevents reversion of neurons into neural stem cells.

Science.gov (United States)

Froldi, Francesca; Szuperak, Milan; Weng, Chen-Fang; Shi, Wei; Papenfuss, Anthony T; Cheng, Louise Y

2015-01-15

Cellular dedifferentiation is the regression of a cell from a specialized state to a more multipotent state and is implicated in cancer. However, the transcriptional network that prevents differentiated cells from reacquiring stem cell fate is so far unclear. Neuroblasts (NBs), the Drosophila neural stem cells, are a model for the regulation of stem cell self-renewal and differentiation. Here we show that the Drosophila zinc finger transcription factor Nervous fingers 1 (Nerfin-1) locks neurons into differentiation, preventing their reversion into NBs. Following Prospero-dependent neuronal specification in the ganglion mother cell (GMC), a Nerfin-1-specific transcriptional program maintains differentiation in the post-mitotic neurons. The loss of Nerfin-1 causes reversion to multipotency and results in tumors in several neural lineages. Both the onset and rate of neuronal dedifferentiation in nerfin-1 mutant lineages are dependent on Myc- and target of rapamycin (Tor)-mediated cellular growth. In addition, Nerfin-1 is required for NB differentiation at the end of neurogenesis. RNA sequencing (RNA-seq) and chromatin immunoprecipitation (ChIP) analysis show that Nerfin-1 administers its function by repression of self-renewing-specific and activation of differentiation-specific genes. Our findings support the model of bidirectional interconvertibility between neural stem cells and their post-mitotic progeny and highlight the importance of the Nerfin-1-regulated transcriptional program in neuronal maintenance. © 2015 Froldi et al.; Published by Cold Spring Harbor Laboratory Press.

Neural processing of speech in children is influenced by bilingual experience

Science.gov (United States)

Krizman, Jennifer; Slater, Jessica; Skoe, Erika; Marian, Viorica; Kraus, Nina

2014-01-01

Language experience fine-tunes how the auditory system processes sound. For example, bilinguals, relative to monolinguals, have more robust evoked responses to speech that manifest as stronger neural encoding of the fundamental frequency (F0) and greater across-trial consistency. However, it is unknown whether such enhancements increase with increasing second language experience. We predict that F0 amplitude and neural consistency scale with dual-language experience during childhood, such that more years of bilingual experience leads to more robust F0 encoding and greater neural consistency. To test this hypothesis, we recorded auditory brainstem responses to the synthesized syllables ‘ba’ and ‘ga’ in two groups of bilingual children who were matched for age at test (8.4+/−0.67 years) but differed in their age of second language acquisition. One group learned English and Spanish simultaneously from birth (n=13), while the second group learned the two languages sequentially (n=15), spending on average their first four years as monolingual Spanish speakers. We find that simultaneous bilinguals have a larger F0 response to ‘ba’ and ‘ga’ and a more consistent response to ‘ba’ compared to sequential bilinguals. We also demonstrate that these neural enhancements positively relate with years of bilingual experience. These findings support the notion that bilingualism enhances subcortical auditory processing. PMID:25445377

FGF8 signaling sustains progenitor status and multipotency of cranial neural crest-derived mesenchymal cells in vivo and in vitro

Science.gov (United States)

Shao, Meiying; Liu, Chao; Song, Yingnan; Ye, Wenduo; He, Wei; Yuan, Guohua; Gu, Shuping; Lin, Congxin; Ma, Liang; Zhang, Yanding; Tian, Weidong; Hu, Tao; Chen, YiPing

2015-01-01

The cranial neural crest (CNC) cells play a vital role in craniofacial development and regeneration. They are multi-potent progenitors, being able to differentiate into various types of tissues. Both pre-migratory and post-migratory CNC cells are plastic, taking on diverse fates by responding to different inductive signals. However, what sustains the multipotency of CNC cells and derivatives remains largely unknown. In this study, we present evidence that FGF8 signaling is able to sustain progenitor status and multipotency of CNC-derived mesenchymal cells both in vivo and in vitro. We show that augmented FGF8 signaling in pre-migratory CNC cells prevents cell differentiation and organogenesis in the craniofacial region by maintaining their progenitor status. CNC-derived mesenchymal cells with Fgf8 overexpression or control cells in the presence of exogenous FGF8 exhibit prolonged survival, proliferation, and multi-potent differentiation capability in cell cultures. Remarkably, exogenous FGF8 also sustains the capability of CNC-derived mesenchymal cells to participate in organogenesis such as odontogenesis. Furthermore, FGF8-mediated signaling strongly promotes adipogenesis but inhibits osteogenesis of CNC-derived mesenchymal cells in vitro. Our results reveal a specific role for FGF8 in the maintenance of progenitor status and in fate determination of CNC cells, implicating a potential application in expansion and fate manipulation of CNC-derived cells in stem cell-based craniofacial regeneration. PMID:26243590

EXPERIMENT BASED FAULT DIAGNOSIS ON BOTTLE FILLING PLANT WITH LVQ ARTIFICIAL NEURAL NETWORK ALGORITHM

Directory of Open Access Journals (Sweden)

Mustafa DEMETGÜL

2008-01-01

Full Text Available In this study, an artificial neural network is developed to find an error rapidly on pneumatic system. Also the ANN prevents the system versus the failure. The error on the experimental bottle filling plant can be defined without any interference using analog values taken from pressure sensors and linear potentiometers. The sensors and potentiometers are placed on different places of the plant. Neural network diagnosis faults on plant, where no bottle, cap closing cylinder B is not working, bottle cap closing cylinder C is not working, air pressure is not sufficient, water is not filling and low air pressure faults. The fault is diagnosed by artificial neural network with LVQ. It is possible to find an failure by using normal programming or PLC. The reason offing Artificial Neural Network is to give a information where the fault is. However, ANN can be used for different systems. The aim is to find the fault by using ANN simultaneously. In this situation, the error taken place on the pneumatic system is collected by a data acquisition card. It is observed that the algorithm is very capable program for many industrial plants which have mechatronic systems.

Dynamic neural network reorganization associated with second language vocabulary acquisition: a multimodal imaging study.

Science.gov (United States)

Hosoda, Chihiro; Tanaka, Kanji; Nariai, Tadashi; Honda, Manabu; Hanakawa, Takashi

2013-08-21

It remains unsettled whether human language relies exclusively on innately privileged brain structure in the left hemisphere or is more flexibly shaped through experiences, which induce neuroplastic changes in potentially relevant neural circuits. Here we show that learning of second language (L2) vocabulary and its cessation can induce bidirectional changes in the mirror-reverse of the traditional language areas. A cross-sectional study identified that gray matter volume in the inferior frontal gyrus pars opercularis (IFGop) and connectivity of the IFGop with the caudate nucleus and the superior temporal gyrus/supramarginal (STG/SMG), predominantly in the right hemisphere, were positively correlated with L2 vocabulary competence. We then implemented a cohort study involving 16 weeks of L2 training in university students. Brain structure before training did not predict the later gain in L2 ability. However, training intervention did increase IFGop volume and reorganization of white matter including the IFGop-caudate and IFGop-STG/SMG pathways in the right hemisphere. These "positive" plastic changes were correlated with the gain in L2 ability in the trained group but were not observed in the control group. We propose that the right hemispheric network can be reorganized into language-related areas through use-dependent plasticity in young adults, reflecting a repertoire of flexible reorganization of the neural substrates responding to linguistic experiences.

Tumour necrosis factor-alpha impairs neuronal differentiation but not proliferation of hippocampal neural precursor cells: Role of Hes1.

Science.gov (United States)

Keohane, Aoife; Ryan, Sinead; Maloney, Eimer; Sullivan, Aideen M; Nolan, Yvonne M

2010-01-01

Tumour necrosis factor-alpha (TNFalpha) is a pro-inflammatory cytokine, which influences neuronal survival and function yet there is limited information available on its effects on hippocampal neural precursor cells (NPCs). We show that TNFalpha treatment during proliferation had no effect on the percentage of proliferating cells prepared from embryonic rat hippocampal neurosphere cultures, nor did it affect cell fate towards either an astrocytic or neuronal lineage when cells were then allowed to differentiate. However, when cells were differentiated in the presence of TNFalpha, significantly reduced percentages of newly born and post-mitotic neurons, significantly increased percentages of astrocytes and increased expression of TNFalpha receptors, TNF-R1 and TNF-R2, as well as expression of the anti-neurogenic Hes1 gene, were observed. These data indicate that exposure of hippocampal NPCs to TNFalpha when they are undergoing differentiation but not proliferation has a detrimental effect on their neuronal lineage fate, which may be mediated through increased expression of Hes1. Copyright 2009 Elsevier Inc. All rights reserved.

Dynamic positional fate map of the primary heart-forming region.

Science.gov (United States)

Cui, Cheng; Cheuvront, Tracey J; Lansford, Rusty D; Moreno-Rodriguez, Ricardo A; Schultheiss, Thomas M; Rongish, Brenda J

2009-08-15

Here we show the temporal-spatial orchestration of early heart morphogenesis at cellular level resolution, in vivo, and reconcile conflicting positional fate mapping data regarding the primary heart-forming field(s). We determined the positional fates of precardiac cells using a precision electroporation approach in combination with wide-field time-lapse microscopy in the quail embryo, a warm-blooded vertebrate (HH Stages 4 through 10). Contrary to previous studies, the results demonstrate the existence of a "continuous" circle-shaped heart field that spans the midline, appearing at HH Stage 4, which then expands to form a wide arc of progenitors at HH Stages 5-7. Our time-resolved image data show that a subset of these cardiac progenitor cells do not overlap with the expression of common cardiogenic factors, Nkx-2.5 and Bmp-2, until HH Stage 10, when a tubular heart has formed, calling into question when cardiac fate is specified and by which key factors. Sub-groups and anatomical bands (cohorts) of heart precursor cells dramatically change their relative positions in a process largely driven by endodermal folding and other large-scale tissue deformations. Thus, our novel dynamic positional fate maps resolve the origin of cardiac progenitor cells in amniotes. The data also establish the concept that tissue motion contributes significantly to cellular position fate - i.e., much of the cellular displacement that occurs during assembly of a midline heart tube (HH Stage 9) is NOT due to "migration" (autonomous motility), a commonly held belief. Computational analysis of our time-resolved data lays the foundation for more precise analyses of how cardiac gene regulatory networks correlate with early heart tissue morphogenesis in birds and mammals.

Speed in Acquisitions

DEFF Research Database (Denmark)

Meglio, Olimpia; King, David R.; Risberg, Annette

2017-01-01

The advantage of speed is often invoked by academics and practitioners as an essential condition during post-acquisition integration, frequently without consideration of the impact earlier decisions have on acquisition speed. In this article, we examine the role speed plays in acquisitions across...... the acquisition process using research organized around characteristics that display complexity with respect to acquisition speed. We incorporate existing research with a process perspective of acquisitions in order to present trade-offs, and consider the influence of both stakeholders and the pre......-deal-completion context on acquisition speed, as well as the organization’s capabilities to facilitating that speed. Observed trade-offs suggest both that acquisition speed often requires longer planning time before an acquisition and that associated decisions require managerial judgement. A framework for improving...

A review of the fate of engineered nanomaterials in municipal solid waste streams.

Science.gov (United States)

Part, Florian; Berge, Nicole; Baran, Paweł; Stringfellow, Anne; Sun, Wenjie; Bartelt-Hunt, Shannon; Mitrano, Denise; Li, Liang; Hennebert, Pierre; Quicker, Peter; Bolyard, Stephanie C; Huber-Humer, Marion

2018-05-01

Significant knowledge and data gaps associated with the fate of product-embedded engineered nanomaterials (ENMs) in waste management processes exist that limit our current ability to develop appropriate end-of-life management strategies. This review paper was developed as part of the activities of the IWWG ENMs in Waste Task Group. The specific objectives of this review paper are to assess the current knowledge associated with the fate of ENMs in commonly used waste management processes, including key processes and mechanisms associated with ENM fate and transport in each waste management process, and to use that information to identify the data gaps and research needs in this area. Literature associated with the fate of ENMs in wastes was reviewed and summarized. Overall, results from this literature review indicate a need for continued research in this area. No work has been conducted to quantify ENMs present in discarded materials and an understanding of ENM release from consumer products under conditions representative of those found in relevant waste management process is needed. Results also indicate that significant knowledge gaps associated with ENM behaviour exist for each waste management process investigated. There is a need for additional research investigating the fate of different types of ENMs at larger concentration ranges with different surface chemistries. Understanding how changes in treatment process operation may influence ENM fate is also needed. A series of specific research questions associated with the fate of ENMs during the management of ENM-containing wastes have been identified and used to direct future research in this area. Copyright © 2018 Elsevier Ltd. All rights reserved.

Continuity and change in children's longitudinal neural responses to numbers.

Science.gov (United States)

Emerson, Robert W; Cantlon, Jessica F

2015-03-01

Human children possess the ability to approximate numerical quantity nonverbally from a young age. Over the course of early childhood, children develop increasingly precise representations of numerical values, including a symbolic number system that allows them to conceive of numerical information as Arabic numerals or number words. Functional brain imaging studies of adults report that activity in bilateral regions of the intraparietal sulcus (IPS) represents a key neural correlate of numerical cognition. Developmental neuroimaging studies indicate that the right IPS develops its number-related neural response profile more rapidly than the left IPS during early childhood. One prediction that can be derived from previous findings is that there is longitudinal continuity in the number-related neural responses of the right IPS over development while the development of the left IPS depends on the acquisition of numerical skills. We tested this hypothesis using fMRI in a longitudinal design with children ages 4 to 9. We found that neural responses in the right IPS are correlated over a 1-2-year period in young children whereas left IPS responses change systematically as a function of children's numerical discrimination acuity. The data are consistent with the hypothesis that functional properties of the right IPS in numerical processing are stable over early childhood whereas the functions of the left IPS are dynamically modulated by the development of numerical skills. © 2014 John Wiley & Sons Ltd.

Fast analysis of spectral data using neural networks

International Nuclear Information System (INIS)

Roach, C.M.

1992-01-01

Fast analysis techniques are highly desirable in experiments where measurements are recorded at high rates. In fusion experiments the processing required to obtain plasma parameters is usually orders of magnitude slower than the data acquisition. Spectroscopic diagnostics suffer greatly from this problem. The extraction of plasma parameters from a measured spectrum typically corresponds to a nonlinear mapping between distinct multi-dimensional spaces. Where no analytic expression for the mapping exists, conventional analysis methods (e.g. least squares) are usually iterative and therefore slow. With this concern in mind a fast spectral analysis method involving neural networks has been investigated. (author) 6 refs., 3 figs

Neural Control of a Tracking Task via Attention-Gated Reinforcement Learning for Brain-Machine Interfaces.

Science.gov (United States)

Wang, Yiwen; Wang, Fang; Xu, Kai; Zhang, Qiaosheng; Zhang, Shaomin; Zheng, Xiaoxiang

2015-05-01

Reinforcement learning (RL)-based brain machine interfaces (BMIs) enable the user to learn from the environment through interactions to complete the task without desired signals, which is promising for clinical applications. Previous studies exploited Q-learning techniques to discriminate neural states into simple directional actions providing the trial initial timing. However, the movements in BMI applications can be quite complicated, and the action timing explicitly shows the intention when to move. The rich actions and the corresponding neural states form a large state-action space, imposing generalization difficulty on Q-learning. In this paper, we propose to adopt attention-gated reinforcement learning (AGREL) as a new learning scheme for BMIs to adaptively decode high-dimensional neural activities into seven distinct movements (directional moves, holdings and resting) due to the efficient weight-updating. We apply AGREL on neural data recorded from M1 of a monkey to directly predict a seven-action set in a time sequence to reconstruct the trajectory of a center-out task. Compared to Q-learning techniques, AGREL could improve the target acquisition rate to 90.16% in average with faster convergence and more stability to follow neural activity over multiple days, indicating the potential to achieve better online decoding performance for more complicated BMI tasks.

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

Science.gov (United States)

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.

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.

2017-01-01

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…

Neural systems underlying aversive conditioning in humans with primary and secondary reinforcers

Directory of Open Access Journals (Sweden)

Mauricio R Delgado

2011-05-01

Full Text Available Money is a secondary reinforcer commonly used across a range of disciplines in experimental paradigms investigating reward learning and decision-making. The effectiveness of monetary reinforcers during aversive learning and its neural basis, however, remains a topic of debate. Specifically, it is unclear if the initial acquisition of aversive representations of monetary losses depends on similar neural systems as more traditional aversive conditioning that involves primary reinforcers. This study contrasts the efficacy of a biologically defined primary reinforcer (shock and a socially defined secondary reinforcer (money during aversive learning and its associated neural circuitry. During a two-part experiment, participants first played a gambling game where wins and losses were based on performance to gain an experimental bank. Participants were then exposed to two separate aversive conditioning sessions. In one session, a primary reinforcer (mild shock served as an unconditioned stimulus (US and was paired with one of two colored squares, the conditioned stimuli (CS+ and CS-, respectively. In another session, a secondary reinforcer (loss of money served as the US and was paired with one of two different CS. Skin conductance responses were greater for CS+ compared to CS- trials irrespective of type of reinforcer. Neuroimaging results revealed that the striatum, a region typically linked with reward-related processing, was found to be involved in the acquisition of aversive conditioned response irrespective of reinforcer type. In contrast, the amygdala was involved during aversive conditioning with primary reinforcers, as suggested by both an exploratory fMRI analysis and a follow-up case study with a patient with bilateral amygdala damage. Taken together, these results suggest that learning about potential monetary losses may depend on reinforcement learning related systems, rather than on typical structures involved in more biologically based

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

Science.gov (United States)

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.

Developing climatic scenarios for pesticide fate modelling in Europe

International Nuclear Information System (INIS)

Blenkinsop, S.; Fowler, H.J.; Dubus, I.G.; Nolan, B.T.; Hollis, J.M.

2008-01-01

A climatic classification for Europe suitable for pesticide fate modelling was constructed using a 3-stage process involving the identification of key climatic variables, the extraction of the dominant modes of spatial variability in those variables and the use of k-means clustering to identify regions with similar climates. The procedure identified 16 coherent zones that reflect the variability of climate across Europe whilst maintaining a manageable number of zones for subsequent modelling studies. An analysis of basic climatic parameters for each zone demonstrates the success of the scheme in identifying distinct climatic regions. Objective criteria were used to identify one representative 26-year daily meteorological series from a European dataset for each zone. The representativeness of each series was then verified against the zonal classifications. These new FOOTPRINT climate zones provide a state-of-the-art objective classification of European climate complete with representative daily data that are suitable for use in pesticide fate modelling. - The FOOTPRINT climatic zones provide an objective climatic classification and daily climate series that may be used for the modelling of pesticide fate across Europe

Comparative Analysis Between Flaviviruses Reveals Specific Neural Stem Cell Tropism for Zika Virus in the Mouse Developing Neocortex

Directory of Open Access Journals (Sweden)

Jean-Baptiste Brault

2016-08-01

Full Text Available The recent Zika outbreak in South America and French Polynesia was associated with an epidemic of microcephaly, a disease characterized by a reduced size of the cerebral cortex. Other members of the Flavivirus genus, including West Nile virus (WNV, can cause encephalitis but were not demonstrated to cause microcephaly. It remains unclear whether Zika virus (ZIKV and other flaviviruses may infect different cell populations in the developing neocortex and lead to distinct developmental defects. Here, we describe an assay to infect mouse E15 embryonic brain slices with ZIKV, WNV and dengue virus serotype 4 (DENV-4. We show that this tissue is able to support viral replication of ZIKV and WNV, but not DENV-4. Cell fate analysis reveals a remarkable tropism of ZIKV infection for neural stem cells. Closely related WNV displays a very different tropism of infection, with a bias towards neurons. We further show that ZIKV infection, but not WNV infection, impairs cell cycle progression of neural stem cells. Both viruses inhibited apoptosis at early stages of infection. This work establishes a powerful comparative approach to identify ZIKV-specific alterations in the developing neocortex and reveals specific preferential infection of neural stem cells by ZIKV.

Fate control and well-being in Chinese rural people living with HIV: mediation effect of resilience.

Science.gov (United States)

Yu, Nancy Xiaonan; Zhang, Jianxin; Chow, Amy Y M; Chan, Celia H Y; Chan, Cecilia L W

2017-01-01

Fate control has been often misconceptualized as a superstitious belief and overlooked in health psychology. It is not known how this cultural belief might impact the well-being of Chinese people living with HIV. This study examined the protective role of fate control for well-being and the potential mediation effect of resilience. Participants in this study were rural patients who contracted HIV via commercial blood donation. In this cross-sectional survey, 250 participants completed measures of fate control, well-being, and resilience. The results showed that fate control and resilience were positively associated with well-being. Resilience mediated the association between fate control and well-being. Our findings provide insight into the adaptive function of fate control as a cognitive defensive mechanism and highlight the need to incorporate this cultural belief in developing culturally sensitive intervention programs for resilience enhancement tailored for this understudied population infected with HIV living in rural China.

Ultra-low noise miniaturized neural amplifier with hardware averaging.

Science.gov (United States)

Dweiri, Yazan M; Eggers, Thomas; McCallum, Grant; Durand, Dominique M

2015-08-01

Peripheral nerves carry neural signals that could be used to control hybrid bionic systems. Cuff electrodes provide a robust and stable interface but the recorded signal amplitude is small (concept of hardware averaging to nerve recordings obtained with cuff electrodes. An optimization procedure is developed to minimize noise and power simultaneously. The novel design was based on existing neural amplifiers (Intan Technologies, LLC) and is validated with signals obtained from the FINE in chronic dog experiments. We showed that hardware averaging leads to a reduction in the total recording noise by a factor of 1/√N or less depending on the source resistance. Chronic recording of physiological activity with FINE using the presented design showed significant improvement on the recorded baseline noise with at least two parallel operation transconductance amplifiers leading to a 46.1% reduction at N = 8. The functionality of these recordings was quantified by the SNR improvement and shown to be significant for N = 3 or more. The present design was shown to be capable of generating hardware averaging on noise improvement for neural recording with cuff electrodes, and can accommodate the presence of high source impedances that are associated with the miniaturized contacts and the high channel count in electrode arrays. This technique can be adopted for other applications where miniaturized and implantable multichannel acquisition systems with ultra-low noise and low power are required.

Social Interaction Affects Neural Outcomes of Sign Language Learning As a Foreign Language in Adults.

Science.gov (United States)

Yusa, Noriaki; Kim, Jungho; Koizumi, Masatoshi; Sugiura, Motoaki; Kawashima, Ryuta

2017-01-01

Children naturally acquire a language in social contexts where they interact with their caregivers. Indeed, research shows that social interaction facilitates lexical and phonological development at the early stages of child language acquisition. It is not clear, however, whether the relationship between social interaction and learning applies to adult second language acquisition of syntactic rules. Does learning second language syntactic rules through social interactions with a native speaker or without such interactions impact behavior and the brain? The current study aims to answer this question. Adult Japanese participants learned a new foreign language, Japanese sign language (JSL), either through a native deaf signer or via DVDs. Neural correlates of acquiring new linguistic knowledge were investigated using functional magnetic resonance imaging (fMRI). The participants in each group were indistinguishable in terms of their behavioral data after the instruction. The fMRI data, however, revealed significant differences in the neural activities between two groups. Significant activations in the left inferior frontal gyrus (IFG) were found for the participants who learned JSL through interactions with the native signer. In contrast, no cortical activation change in the left IFG was found for the group who experienced the same visual input for the same duration via the DVD presentation. Given that the left IFG is involved in the syntactic processing of language, spoken or signed, learning through social interactions resulted in an fMRI signature typical of native speakers: activation of the left IFG. Thus, broadly speaking, availability of communicative interaction is necessary for second language acquisition and this results in observed changes in the brain.

Neural predictors of individual differences in response to math tutoring in primary-grade school children.

Science.gov (United States)

Supekar, Kaustubh; Swigart, Anna G; Tenison, Caitlin; Jolles, Dietsje D; Rosenberg-Lee, Miriam; Fuchs, Lynn; Menon, Vinod

2013-05-14

Now, more than ever, the ability to acquire mathematical skills efficiently is critical for academic and professional success, yet little is known about the behavioral and neural mechanisms that drive some children to acquire these skills faster than others. Here we investigate the behavioral and neural predictors of individual differences in arithmetic skill acquisition in response to 8-wk of one-to-one math tutoring. Twenty-four children in grade 3 (ages 8-9 y), a critical period for acquisition of basic mathematical skills, underwent structural and resting-state functional MRI scans pretutoring. A significant shift in arithmetic problem-solving strategies from counting to fact retrieval was observed with tutoring. Notably, the speed and accuracy of arithmetic problem solving increased with tutoring, with some children improving significantly more than others. Next, we examined whether pretutoring behavioral and brain measures could predict individual differences in arithmetic performance improvements with tutoring. No behavioral measures, including intelligence quotient, working memory, or mathematical abilities, predicted performance improvements. In contrast, pretutoring hippocampal volume predicted performance improvements. Furthermore, pretutoring intrinsic functional connectivity of the hippocampus with dorsolateral and ventrolateral prefrontal cortices and the basal ganglia also predicted performance improvements. Our findings provide evidence that individual differences in morphometry and connectivity of brain regions associated with learning and memory, and not regions typically involved in arithmetic processing, are strong predictors of responsiveness to math tutoring in children. More generally, our study suggests that quantitative measures of brain structure and intrinsic brain organization can provide a more sensitive marker of skill acquisition than behavioral measures.

Neural network control of focal position during time-lapse microscopy of cells.

Science.gov (United States)

Wei, Ling; Roberts, Elijah

2018-05-09

Live-cell microscopy is quickly becoming an indispensable technique for studying the dynamics of cellular processes. Maintaining the specimen in focus during image acquisition is crucial for high-throughput applications, especially for long experiments or when a large sample is being continuously scanned. Automated focus control methods are often expensive, imperfect, or ill-adapted to a specific application and are a bottleneck for widespread adoption of high-throughput, live-cell imaging. Here, we demonstrate a neural network approach for automatically maintaining focus during bright-field microscopy. Z-stacks of yeast cells growing in a microfluidic device were collected and used to train a convolutional neural network to classify images according to their z-position. We studied the effect on prediction accuracy of the various hyperparameters of the neural network, including downsampling, batch size, and z-bin resolution. The network was able to predict the z-position of an image with ±1 μm accuracy, outperforming human annotators. Finally, we used our neural network to control microscope focus in real-time during a 24 hour growth experiment. The method robustly maintained the correct focal position compensating for 40 μm of focal drift and was insensitive to changes in the field of view. About ~100 annotated z-stacks were required to train the network making our method quite practical for custom autofocus applications.

Diagnosis of fetal neural tube defects by MRI

International Nuclear Information System (INIS)

Dong Suzhen; Zhu Ming; Zhong Yumin; Zhang Hong; Pan Huihong

2010-01-01

Objective: To explore the diagnostic value of MRI on fetal neural tube defects. Methods: Ten pregnant women, aged from 25 to 35 years (average 28 years) and with gestation from 20-39 weeks (average 33 weeks) were studied with a 1.5 T superconductive MR unit within 24 to 48 hours after ultrasound (US) studies. The imaging protocol included fast-imaging employing steady-state acquisition, single-shot FSE and T 1 -weighted fast inversion recovery motion insensitive sequences in the axial, fromtal, and sagittal planes relative to the fetal brain, thorax, abdomen, and spines. Prenatal US and MRI findings were compared with postnatal MRI diagnoses (3 fetuses) or autopsy (7 fetuses). Results: Ten pregnant women (9 with a single fetus and 1 with twin fetuses) were examined. For all cases, the diagnoses established by MRI were correct when compared with postnatal diagnosis or autopsy. In 7 cases, US and MRI findings were in complete agreement with postnatal diagnoses. US missed the diagnosis in 1 cases and misdiagnosed in 2 cases. Ten neural tube defects in this study included anencephaly (1 case), exencephaly (1 case), meningoencephalocele associated with amniotic band sequence (1 case), meningocele (1 case), thoracic myelomeningocele (1 case), lumbar spinal bifida (1 case), sacroiliac myelomeningocele (2 cases), sacroiliac large cystic spinal meningocele (1 case), sacroiliac spinal bifida (1 case). Conclusions: Prenatal MRI is effective in the assessment of fetal neural tube defects. It can exactly discriminate herniated contents and locate the spinal lesion level. (authors)

Using hardware models to quantify sensory data acquisition across the rat vibrissal array.

Science.gov (United States)

Gopal, Venkatesh; Hartmann, Mitra J Z

2007-12-01

Our laboratory investigates how animals acquire sensory data to understand the neural computations that permit complex sensorimotor behaviors. We use the rat whisker system as a model to study active tactile sensing; our aim is to quantitatively describe the spatiotemporal structure of incoming sensory information to place constraints on subsequent neural encoding and processing. In the first part of this paper we describe the steps in the development of a hardware model (a 'sensobot') of the rat whisker array that can perform object feature extraction. We show how this model provides insights into the neurophysiology and behavior of the real animal. In the second part of this paper, we suggest that sensory data acquisition across the whisker array can be quantified using the complete derivative. We use the example of wall-following behavior to illustrate that computing the appropriate spatial gradients across a sensor array would enable an animal or mobile robot to predict the sensory data that will be acquired at the next time step.

Nonsense-Mediated RNA Decay Influences Human Embryonic Stem Cell Fate

Directory of Open Access Journals (Sweden)

Chih-Hong Lou

2016-06-01

Full Text Available Nonsense-mediated RNA decay (NMD is a highly conserved pathway that selectively degrades specific subsets of RNA transcripts. Here, we provide evidence that NMD regulates early human developmental cell fate. We found that NMD factors tend to be expressed at higher levels in human pluripotent cells than in differentiated cells, raising the possibility that NMD must be downregulated to permit differentiation. Loss- and gain-of-function experiments in human embryonic stem cells (hESCs demonstrated that, indeed, NMD downregulation is essential for efficient generation of definitive endoderm. RNA-seq analysis identified NMD target transcripts induced when NMD is suppressed in hESCs, including many encoding signaling components. This led us to test the role of TGF-β and BMP signaling, which we found NMD acts through to influence definitive endoderm versus mesoderm fate. Our results suggest that selective RNA decay is critical for specifying the developmental fate of specific human embryonic cell lineages.

The Effect of Agmatine on Expression of IL-1β and TLX Which Promotes Neuronal Differentiation in Lipopolysaccharide-Treated Neural Progenitors.

Science.gov (United States)

Song, Juhyun; Kumar, Bokara Kiran; Kang, Somang; Park, Kyung Ah; Lee, Won Taek; Lee, Jong Eun

2013-12-01

Differentiation of neural progenitor cells (NPCs) is important for protecting neural cells and brain tissue during inflammation. Interleukin-1 beta (IL-1β) is the most common pro- inflammatory cytokine in brain inflammation, and increased IL-1β levels can decrease the proliferation of NPCs. We aimed to investigate whether agmatine (Agm), a primary polyamine that protects neural cells, could trigger differentiation of NPCs by activating IL-1β in vitro. The cortex of ICR mouse embryos (E14) was dissociated to culture NPCs. NPCs were stimulated by lipopolysaccharide (LPS). After 6 days, protein expression of stem cell markers and differentiation signal factors was confirmed by using western blot analysis. Also, immunocytochemistry was used to confirm the cell fate. Agm treatment activated NPC differentiation significantly more than in the control group, which was evident by the increased expression of a neuronal marker, MAP2, in the LPS-induced, Agm-treated group. Differentiation of LPS-induced, Agm-treated NPCs was regulated by the MAPK pathway and is thought to be related to IL-1β activation and decreased expression of TLX, a transcription factor that regulates NPC differentiation. Our results reveal that Agm can promote NPC differentiation to neural stem cells by modulating IL-1β expression under inflammatory condition, and they suggest that Agm may be a novel therapeutic strategy for neuroinflammatory diseases.

Concealed, Unobtrusive Ear-Centered EEG Acquisition: cEEGrids for Transparent EEG

Science.gov (United States)

Bleichner, Martin G.; Debener, Stefan

2017-01-01

Electroencephalography (EEG) is an important clinical tool and frequently used to study the brain-behavior relationship in humans noninvasively. Traditionally, EEG signals are recorded by positioning electrodes on the scalp and keeping them in place with glue, rubber bands, or elastic caps. This setup provides good coverage of the head, but is impractical for EEG acquisition in natural daily-life situations. Here, we propose the transparent EEG concept. Transparent EEG aims for motion tolerant, highly portable, unobtrusive, and near invisible data acquisition with minimum disturbance of a user's daily activities. In recent years several ear-centered EEG solutions that are compatible with the transparent EEG concept have been presented. We discuss work showing that miniature electrodes placed in and around the human ear are a feasible solution, as they are sensitive enough to pick up electrical signals stemming from various brain and non-brain sources. We also describe the cEEGrid flex-printed sensor array, which enables unobtrusive multi-channel EEG acquisition from around the ear. In a number of validation studies we found that the cEEGrid enables the recording of meaningful continuous EEG, event-related potentials and neural oscillations. Here, we explain the rationale underlying the cEEGrid ear-EEG solution, present possible use cases and identify open issues that need to be solved on the way toward transparent EEG. PMID:28439233

The linear interplay of intrinsic and extrinsic noises ensures a high accuracy of cell fate selection in budding yeast

Science.gov (United States)

Li, Yongkai; Yi, Ming; Zou, Xiufen

2014-01-01

To gain insights into the mechanisms of cell fate decision in a noisy environment, the effects of intrinsic and extrinsic noises on cell fate are explored at the single cell level. Specifically, we theoretically define the impulse of Cln1/2 as an indication of cell fates. The strong dependence between the impulse of Cln1/2 and cell fates is exhibited. Based on the simulation results, we illustrate that increasing intrinsic fluctuations causes the parallel shift of the separation ratio of Whi5P but that increasing extrinsic fluctuations leads to the mixture of different cell fates. Our quantitative study also suggests that the strengths of intrinsic and extrinsic noises around an approximate linear model can ensure a high accuracy of cell fate selection. Furthermore, this study demonstrates that the selection of cell fates is an entropy-decreasing process. In addition, we reveal that cell fates are significantly correlated with the range of entropy decreases. PMID:25042292

Smart acquisition EELS

International Nuclear Information System (INIS)

Sader, Kasim; Schaffer, Bernhard; Vaughan, Gareth; Brydson, Rik; Brown, Andy; Bleloch, Andrew

2010-01-01

We have developed a novel acquisition methodology for the recording of electron energy loss spectra (EELS) using a scanning transmission electron microscope (STEM): 'Smart Acquisition'. Smart Acquisition allows the independent control of probe scanning procedures and the simultaneous acquisition of analytical signals such as EELS. The original motivation for this work arose from the need to control the electron dose experienced by beam-sensitive specimens whilst maintaining a sufficiently high signal-to-noise ratio in the EEL signal for the extraction of useful analytical information (such as energy loss near edge spectral features) from relatively undamaged areas. We have developed a flexible acquisition framework which separates beam position data input, beam positioning, and EELS acquisition. In this paper we demonstrate the effectiveness of this technique on beam-sensitive thin films of amorphous aluminium trifluoride. Smart Acquisition has been used to expose lines to the electron beam, followed by analysis of the structures created by line-integrating EELS acquisitions, and the results are compared to those derived from a standard EELS linescan. High angle annular dark-field images show clear reductions in damage for the Smart Acquisition areas compared to the conventional linescan, and the Smart Acquisition low loss EEL spectra are more representative of the undamaged material than those derived using a conventional linescan. Atomically resolved EELS of all four elements of CaNdTiO show the high resolution capabilities of Smart Acquisition.

Smart acquisition EELS

Energy Technology Data Exchange (ETDEWEB)

Sader, Kasim, E-mail: k.sader@leeds.ac.uk [SuperSTEM, J block, Daresbury Laboratory, Warrington, Cheshire, WA4 4AD (United Kingdom); Institute for Materials Research, University of Leeds, LS2 9JT (United Kingdom); Schaffer, Bernhard [SuperSTEM, J block, Daresbury Laboratory, Warrington, Cheshire, WA4 4AD (United Kingdom); Department of Physics and Astronomy, University of Glasgow (United Kingdom); Vaughan, Gareth [Institute for Materials Research, University of Leeds, LS2 9JT (United Kingdom); Brydson, Rik [SuperSTEM, J block, Daresbury Laboratory, Warrington, Cheshire, WA4 4AD (United Kingdom); Institute for Materials Research, University of Leeds, LS2 9JT (United Kingdom); Brown, Andy [Institute for Materials Research, University of Leeds, LS2 9JT (United Kingdom); Bleloch, Andrew [SuperSTEM, J block, Daresbury Laboratory, Warrington, Cheshire, WA4 4AD (United Kingdom); Department of Engineering, University of Liverpool, Liverpool (United Kingdom)

2010-07-15

We have developed a novel acquisition methodology for the recording of electron energy loss spectra (EELS) using a scanning transmission electron microscope (STEM): 'Smart Acquisition'. Smart Acquisition allows the independent control of probe scanning procedures and the simultaneous acquisition of analytical signals such as EELS. The original motivation for this work arose from the need to control the electron dose experienced by beam-sensitive specimens whilst maintaining a sufficiently high signal-to-noise ratio in the EEL signal for the extraction of useful analytical information (such as energy loss near edge spectral features) from relatively undamaged areas. We have developed a flexible acquisition framework which separates beam position data input, beam positioning, and EELS acquisition. In this paper we demonstrate the effectiveness of this technique on beam-sensitive thin films of amorphous aluminium trifluoride. Smart Acquisition has been used to expose lines to the electron beam, followed by analysis of the structures created by line-integrating EELS acquisitions, and the results are compared to those derived from a standard EELS linescan. High angle annular dark-field images show clear reductions in damage for the Smart Acquisition areas compared to the conventional linescan, and the Smart Acquisition low loss EEL spectra are more representative of the undamaged material than those derived using a conventional linescan. Atomically resolved EELS of all four elements of CaNdTiO show the high resolution capabilities of Smart Acquisition.

Imaging the neural circuitry and chemical control of aggressive motivation

Directory of Open Access Journals (Sweden)

Blanchard D Caroline

2008-11-01

Full Text Available Abstract Background With the advent of functional magnetic resonance imaging (fMRI in awake animals it is possible to resolve patterns of neuronal activity across the entire brain with high spatial and temporal resolution. Synchronized changes in neuronal activity across multiple brain areas can be viewed as functional neuroanatomical circuits coordinating the thoughts, memories and emotions for particular behaviors. To this end, fMRI in conscious rats combined with 3D computational analysis was used to identifying the putative distributed neural circuit involved in aggressive motivation and how this circuit is affected by drugs that block aggressive behavior. Results To trigger aggressive motivation, male rats were presented with their female cage mate plus a novel male intruder in the bore of the magnet during image acquisition. As expected, brain areas previously identified as critical in the organization and expression of aggressive behavior were activated, e.g., lateral hypothalamus, medial basal amygdala. Unexpected was the intense activation of the forebrain cortex and anterior thalamic nuclei. Oral administration of a selective vasopressin V1a receptor antagonist SRX251 or the selective serotonin reuptake inhibitor fluoxetine, drugs that block aggressive behavior, both caused a general suppression of the distributed neural circuit involved in aggressive motivation. However, the effect of SRX251, but not fluoxetine, was specific to aggression as brain activation in response to a novel sexually receptive female was unaffected. Conclusion The putative neural circuit of aggressive motivation identified with fMRI includes neural substrates contributing to emotional expression (i.e. cortical and medial amygdala, BNST, lateral hypothalamus, emotional experience (i.e. hippocampus, forebrain cortex, anterior cingulate, retrosplenial cortex and the anterior thalamic nuclei that bridge the motor and cognitive components of aggressive responding

Modelling the Fate of Xenobiotic Trace Chemicals via Wastewater Treatment and Agricultural Resource Reuse

DEFF Research Database (Denmark)

Polesel, Fabio

the comprehension of XTC fate, and thus the predictive capabilities of fate models: (i) at process scale, with a focus on sorption and biological transformation of XTCs in biological treatment systems; (ii) in full-scale WWTPs, assessing the impact of retransformation and WWTP operation on XTC elimination; and (iii......) in integrated WWTP-agricultural systems. Different modelling tools, suiting the specific purposes of our investigations, were developed, extended and/or innovatively applied. Fate models used as reference in this thesis include: the Activated Sludge Modelling framework for Xenobiotics (ASM-X); the generic WWTP...... model SimpleTreat Activity; and the dynamic soil-plant model for fate prediction in agricultural systems. Experimental and model-based observations were combined to assess sorption of ionizable XTCs onto activated sludge and XTC biotransformation in moving bed biofilm reactors (MBBRs). Most XTCs...

Somatosensory cortices are required for the acquisition of morphine-induced conditioned place preference.

Directory of Open Access Journals (Sweden)

Zhiqiang Meng

Full Text Available BACKGROUND: Sensory system information is thought to play an important role in drug addiction related responses. However, how somatic sensory information participates in the drug related behaviors is still unclear. Many studies demonstrated that drug addiction represents a pathological usurpation of neural mechanisms of learning and memory that normally relate to the pursuit of rewards. Thus, elucidate the role of somatic sensory in drug related learning and memory is of particular importance to understand the neurobiological mechanisms of drug addiction. PRINCIPAL FINDINGS: In the present study, we investigated the role of somatosensory system in reward-related associative learning using the conditioned place preference model. Lesions were made in somatosensory cortices either before or after conditioning training. We found that lesion of somatosensory cortices before, rather than after morphine conditioning impaired the acquisition of place preference. CONCLUSION: These results demonstrate that somatosensory cortices are necessary for the acquisition but not retention of morphine induced place preference.

Combining Multiple Data Acquisition Systems to Study Corticospinal Output and Multi-segment Biomechanics.

Science.gov (United States)

Asmussen, Michael J; Bailey, Aaron Z; Keir, Peter J; Potvin, Jim; Bergel, Tim; Nelson, Aimee J

2016-01-09

Transcranial magnetic stimulation techniques allow for an in-depth investigation into the neural mechanisms that underpin human behavior. To date, the use of TMS to study human movement, has been limited by the challenges related to precisely timing the delivery of TMS to features of the unfolding movement and, also, by accurately characterizing kinematics and kinetics. To overcome these technical challenges, TMS delivery and acquisition systems should be integrated with an online motion tracking system. The present manuscript details technical innovations that integrate multiple acquisition systems to facilitate and advance the use of TMS to study human movement. Using commercially available software and hardware systems, a step-by-step approach to both the hardware assembly and the software scripts necessary to perform TMS studies triggered by specific features of a movement is provided. The approach is focused on the study of upper limb, planar, multi-joint reaching movements. However, the same integrative system is amenable to a multitude of sophisticated studies of human motor control.

Language Acquisition without an Acquisition Device

Science.gov (United States)

O'Grady, William

2012-01-01

Most explanatory work on first and second language learning assumes the primacy of the acquisition phenomenon itself, and a good deal of work has been devoted to the search for an "acquisition device" that is specific to humans, and perhaps even to language. I will consider the possibility that this strategy is misguided and that language…

Challenges in assessing the environmental fate and exposure of nano silver

International Nuclear Information System (INIS)

Whiteley, Cherrie M; Jones, Kevin C; Sweetman, Andy J; Dalla Valle, Matteo

2011-01-01

There are significant challenges in assessing the fate and exposure of nano particles (NPs) owing to the lack of information on their use and potential pathways and sinks in the environment. This paper discusses these issues using nanosilver as a case study. The approach taken is to assess the production of nanosilver, the range of products that utilise its properties, potential environmental release pathways and subsequent fate. Estimates of UK nanosilver released into the environment have been made and sewage sludge identified as an important receiving compartment. This work aims to highlight the on-going challenges faced when assessing NPs in the environment. Using nanosilver as an example, difficulties in assessing production, use and release are discussed. The study also recommends a potential approach to assess the fate and behaviour assessment of nanosilver in the environment.

Insights into bird wing evolution and digit specification from polarizing region fate maps.

Science.gov (United States)

Towers, Matthew; Signolet, Jason; Sherman, Adrian; Sang, Helen; Tickle, Cheryll

2011-08-09

The proposal that birds descended from theropod dinosaurs with digits 2, 3 and 4 was recently given support by short-term fate maps, suggesting that the chick wing polarizing region-a group that Sonic hedgehog-expressing cells-gives rise to digit 4. Here we show using long-term fate maps that Green fluorescent protein-expressing chick wing polarizing region grafts contribute only to soft tissues along the posterior margin of digit 4, supporting fossil data that birds descended from theropods that had digits 1, 2 and 3. In contrast, digit IV of the chick leg with four digits (I-IV) arises from the polarizing region. To determine how digit identity is specified over time, we inhibited Sonic hedgehog signalling. Fate maps show that polarizing region and adjacent cells are specified in parallel through a series of anterior to posterior digit fates-a process of digit specification that we suggest is involved in patterning all vertebrate limbs with more than three digits.

Post-Acquisition IT Integration

DEFF Research Database (Denmark)

Henningsson, Stefan; Yetton, Philip

2013-01-01

The extant research on post-acquisition IT integration analyzes how acquirers realize IT-based value in individual acquisitions. However, serial acquirers make 60% of acquisitions. These acquisitions are not isolated events, but are components in growth-by-acquisition programs. To explain how...... serial acquirers realize IT-based value, we develop three propositions on the sequential effects on post-acquisition IT integration in acquisition programs. Their combined explanation is that serial acquirers must have a growth-by-acquisition strategy that includes the capability to improve...... IT integration capabilities, to sustain high alignment across acquisitions and to maintain a scalable IT infrastructure with a flat or decreasing cost structure. We begin the process of validating the three propositions by investigating a longitudinal case study of a growth-by-acquisition program....

PI[subscript 3]-Kinase Cascade Has a Differential Role in Acquisition and Extinction of Conditioned Fear Memory in Juvenile and Adult Rats

Science.gov (United States)

Slouzkey, Ilana; Maroun, Mouna

2016-01-01

The basolateral amygdala (BLA), medial prefrontal cortex (mPFC) circuit, plays a crucial role in acquisition and extinction of fear memory. Extinction of aversive memories is mediated, at least in part, by the phosphoinositide-3 kinase (P[subscript 3]K)/Akt pathway in adult rats. There is recent interest in the neural mechanisms that mediate fear…

The neural basis of the imitation drive.

Science.gov (United States)

Hanawa, Sugiko; Sugiura, Motoaki; Nozawa, Takayuki; Kotozaki, Yuka; Yomogida, Yukihito; Ihara, Mizuki; Akimoto, Yoritaka; Thyreau, Benjamin; Izumi, Shinichi; Kawashima, Ryuta

2016-01-01

Spontaneous imitation is assumed to underlie the acquisition of important skills by infants, including language and social interaction. In this study, functional magnetic resonance imaging (fMRI) was used to examine the neural basis of 'spontaneously' driven imitation, which has not yet been fully investigated. Healthy participants were presented with movie clips of meaningless bimanual actions and instructed to observe and imitate them during an fMRI scan. The participants were subsequently shown the movie clips again and asked to evaluate the strength of their 'urge to imitate' (Urge) for each action. We searched for cortical areas where the degree of activation positively correlated with Urge scores; significant positive correlations were observed in the right supplementary motor area (SMA) and bilateral midcingulate cortex (MCC) under the imitation condition. These areas were not explained by explicit reasons for imitation or the kinematic characteristics of the actions. Previous studies performed in monkeys and humans have implicated the SMA and MCC/caudal cingulate zone in voluntary actions. This study also confirmed the functional connectivity between Urge and imitation performance using a psychophysiological interaction analysis. Thus, our findings reveal the critical neural components that underlie spontaneous imitation and provide possible reasons why infants imitate spontaneously. © The Author (2015). Published by Oxford University Press.

Chemicals as the Sole Transformers of Cell Fate.

Science.gov (United States)

Ebrahimi, Behnam

2016-05-30

Forced expression of lineage-specific transcription factors in somatic cells can result in the generation of different cell types in a process named direct reprogramming, bypassing the pluripotent state. However, the introduction of transgenes limits the therapeutic applications of the produced cells. Numerous small-molecules have been introduced in the field of stem cell biology capable of governing self-renewal, reprogramming, transdifferentiation and regeneration. These chemical compounds are versatile tools for cell fate conversion toward desired outcomes. Cell fate conversion using small-molecules alone (chemical reprogramming) has superiority over arduous traditional genetic techniques in several aspects. For instance, rapid, transient, and reversible effects in activation and inhibition of functions of specific proteins are of the profits of small-molecules. They are cost-effective, have a long half-life, diversity on structure and function, and allow for temporal and flexible regulation of signaling pathways. Additionally, their effects could be adjusted by fine-tuning concentrations and combinations of different small-molecules. Therefore, chemicals are powerful tools in cell fate conversion and study of stem cell and chemical biology in vitro and in vivo. Moreover, transgene-free and chemical-only transdifferentiation approaches provide alternative strategies for the generation of various cell types, disease modeling, drug screening, and regenerative medicine. The current review gives an overview of the recent findings concerning transdifferentiation by only small-molecules without the use of transgenes.

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.

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.

Logic programming to predict cell fate patterns and retrodict genotypes in organogenesis.

Science.gov (United States)

Hall, Benjamin A; Jackson, Ethan; Hajnal, Alex; Fisher, Jasmin

2014-09-06

Caenorhabditis elegans vulval development is a paradigm system for understanding cell differentiation in the process of organogenesis. Through temporal and spatial controls, the fate pattern of six cells is determined by the competition of the LET-23 and the Notch signalling pathways. Modelling cell fate determination in vulval development using state-based models, coupled with formal analysis techniques, has been established as a powerful approach in predicting the outcome of combinations of mutations. However, computing the outcomes of complex and highly concurrent models can become prohibitive. Here, we show how logic programs derived from state machines describing the differentiation of C. elegans vulval precursor cells can increase the speed of prediction by four orders of magnitude relative to previous approaches. Moreover, this increase in speed allows us to infer, or 'retrodict', compatible genomes from cell fate patterns. We exploit this technique to predict highly variable cell fate patterns resulting from dig-1 reduced-function mutations and let-23 mosaics. In addition to the new insights offered, we propose our technique as a platform for aiding the design and analysis of experimental data. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

IDH1R132H in Neural Stem Cells: Differentiation Impaired by Increased Apoptosis.

Directory of Open Access Journals (Sweden)

Kamila Rosiak

Full Text Available The high frequency of mutations in the isocitrate dehydrogenase 1 (IDH1 gene in diffuse gliomas indicates its importance in the process of gliomagenesis. These mutations result in loss of the normal function and acquisition of the neomorphic activity converting α-ketoglutarate to 2-hydroxyglutarate. This potential oncometabolite may induce the epigenetic changes, resulting in the deregulated expression of numerous genes, including those related to the differentiation process or cell survivability.Neural stem cells were derived from human induced pluripotent stem cells following embryoid body formation. Neural stem cells transduced with mutant IDH1R132H, empty vector, non-transduced and overexpressing IDH1WT controls were differentiated into astrocytes and neurons in culture. The neuronal and astrocytic differentiation was determined by morphology and expression of lineage specific markers (MAP2, Synapsin I and GFAP as determined by real-time PCR and immunocytochemical staining. Apoptosis was evaluated by real-time observation of Caspase-3 activation and measurement of PARP cleavage by Western Blot.Compared with control groups, cells expressing IDH1R132H retained an undifferentiated state and lacked morphological changes following stimulated differentiation. The significant inhibitory effect of IDH1R132H on neuronal and astrocytic differentiation was confirmed by immunocytochemical staining for markers of neural stem cells. Additionally, real-time PCR indicated suppressed expression of lineage markers. High percentage of apoptotic cells was detected within IDH1R132H-positive neural stem cells population and their derivatives, if compared to normal neural stem cells and their derivatives. The analysis of PARP and Caspase-3 activity confirmed apoptosis sensitivity in mutant protein-expressing neural cells.Our study demonstrates that expression of IDH1R132H increases apoptosis susceptibility of neural stem cells and their derivatives. Robust

Biologically based neural circuit modelling for the study of fear learning and extinction

Science.gov (United States)

Nair, Satish S.; Paré, Denis; Vicentic, Aleksandra

2016-11-01

The neuronal systems that promote protective defensive behaviours have been studied extensively using Pavlovian conditioning. In this paradigm, an initially neutral-conditioned stimulus is paired with an aversive unconditioned stimulus leading the subjects to display behavioural signs of fear. Decades of research into the neural bases of this simple behavioural paradigm uncovered that the amygdala, a complex structure comprised of several interconnected nuclei, is an essential part of the neural circuits required for the acquisition, consolidation and expression of fear memory. However, emerging evidence from the confluence of electrophysiological, tract tracing, imaging, molecular, optogenetic and chemogenetic methodologies, reveals that fear learning is mediated by multiple connections between several amygdala nuclei and their distributed targets, dynamical changes in plasticity in local circuit elements as well as neuromodulatory mechanisms that promote synaptic plasticity. To uncover these complex relations and analyse multi-modal data sets acquired from these studies, we argue that biologically realistic computational modelling, in conjunction with experiments, offers an opportunity to advance our understanding of the neural circuit mechanisms of fear learning and to address how their dysfunction may lead to maladaptive fear responses in mental disorders.

Predicting the fate of micropollutants during wastewater treatment: Calibration and sensitivity analysis.

Science.gov (United States)

Baalbaki, Zeina; Torfs, Elena; Yargeau, Viviane; Vanrolleghem, Peter A

2017-12-01

The presence of micropollutants in the environment and their toxic impacts on the aquatic environment have raised concern about their inefficient removal in wastewater treatment plants. In this study, the fate of micropollutants of four different classes was simulated in a conventional activated sludge plant using a bioreactor micropollutant fate model coupled to a settler model. The latter was based on the Bürger-Diehl model extended for the first time to include micropollutant fate processes. Calibration of model parameters was completed by matching modelling results with full-scale measurements (i.e. including aqueous and particulate phase concentrations of micropollutants) obtained from a 4-day sampling campaign. Modelling results showed that further biodegradation takes place in the sludge blanket of the settler for the highly biodegradable caffeine, underlining the need for a reactive settler model. The adopted Monte Carlo based calibration approach also provided an overview of the model's global sensitivity to the parameters. This analysis showed that for each micropollutant and according to the dominant fate process, a different set of one or more parameters had a significant impact on the model fit, justifying the selection of parameter subsets for model calibration. A dynamic local sensitivity analysis was also performed with the calibrated parameters. This analysis supported the conclusions from the global sensitivity and provided guidance for future sampling campaigns. This study expands the understanding of micropollutant fate models when applied to different micropollutants, in terms of global and local sensitivity to model parameters, as well as the identifiability of the parameters. Copyright © 2017 Elsevier B.V. All rights reserved.

MicroRNA Cluster miR-17-92 Regulates Neural Stem Cell Expansion and Transition to Intermediate Progenitors in the Developing Mouse Neocortex

Directory of Open Access Journals (Sweden)

Shan Bian

2013-05-01

Full Text Available During development of the embryonic neocortex, tightly regulated expansion of neural stem cells (NSCs and their transition to intermediate progenitors (IPs are critical for normal cortical formation and function. Molecular mechanisms that regulate NSC expansion and transition remain unclear. Here, we demonstrate that the microRNA (miRNA miR-17-92 cluster is required for maintaining proper populations of cortical radial glial cells (RGCs and IPs through repression of Pten and Tbr2 protein. Knockout of miR-17-92 and its paralogs specifically in the developing neocortex restricts NSC proliferation, suppresses RGC expansion, and promotes transition of RGCs to IPs. Moreover, Pten and Tbr2 protectors specifically block silencing activities of endogenous miR-17-92 and control proper numbers of RGCs and IPs in vivo. Our results demonstrate a critical role for miRNAs in promoting NSC proliferation and modulating the cell-fate decision of generating distinct neural progenitors in the developing neocortex.

EVALUATION OF THE STATE-OF-THE-ART CONTAMINATED SEDIMENT TRANSPORT AND FATE MODELING SYSTEM

Science.gov (United States)

Modeling approaches for evaluating the transport and fate of sediment and associated contaminants are briefly reviewed. The main emphasis is on: 1) the application of EFDC (Environmental Fluid Dynamics Code), the state-of-the-art contaminated sediment transport and fate public do...

Neurally and mathematically motivated architecture for language and thought.

Science.gov (United States)

Perlovsky, L I; Ilin, R

2010-01-01

Neural structures of interaction between thinking and language are unknown. This paper suggests a possible architecture motivated by neural and mathematical considerations. A mathematical requirement of computability imposes significant constraints on possible architectures consistent with brain neural structure and with a wealth of psychological knowledge. How language interacts with cognition. Do we think with words, or is thinking independent from language with words being just labels for decisions? Why is language learned by the age of 5 or 7, but acquisition of knowledge represented by learning to use this language knowledge takes a lifetime? This paper discusses hierarchical aspects of language and thought and argues that high level abstract thinking is impossible without language. We discuss a mathematical technique that can model the joint language-thought architecture, while overcoming previously encountered difficulties of computability. This architecture explains a contradiction between human ability for rational thoughtful decisions and irrationality of human thinking revealed by Tversky and Kahneman; a crucial role in this contradiction might be played by language. The proposed model resolves long-standing issues: how the brain learns correct words-object associations; why animals do not talk and think like people. We propose the role played by language emotionality in its interaction with thought. We relate the mathematical model to Humboldt's "firmness" of languages; and discuss possible influence of language grammar on its emotionality. Psychological and brain imaging experiments related to the proposed model are discussed. Future theoretical and experimental research is outlined.

The environmental release and fate of antibiotics.

Science.gov (United States)

Manzetti, Sergio; Ghisi, Rossella

2014-02-15

Antibiotics have been used as medical remedies for over 50 years and have recently emerged as new pollutants in the environment. This review encompasses the fate of several antibiotics in the environment, including sulfonamides, nitrofurans, terfenadines, cephalosporins and cyclosporins. It investigates the cycle of transfer from humans and animals including their metabolic transformation. The results show that antibiotic metabolites are of considerable persistence and are localized to ground-water and drinking water supplies. Furthermore, the results also show that several phases of the cycle of antibiotics in the environment are not well understood, such as how low concentrations of antibiotic metabolites in the diet affect humans and animals. This review also shows that improved wastewater decontamination processes are remediating factors for these emerging pollutants. The results obtained here may help legislators and authorities in understanding the fate and transformation of antibiotics in the environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Distinct regulatory functions of calpain 1 and 2 during neural stem cell self-renewal and differentiation.

Directory of Open Access Journals (Sweden)

Daniela M Santos

Full Text Available Calpains are calcium regulated cysteine proteases that have been described in a wide range of cellular processes, including apoptosis, migration and cell cycle regulation. In addition, calpains have been implicated in differentiation, but their impact on neural differentiation requires further investigation. Here, we addressed the role of calpain 1 and calpain 2 in neural stem cell (NSC self-renewal and differentiation. We found that calpain inhibition using either the chemical inhibitor calpeptin or the endogenous calpain inhibitor calpastatin favored differentiation of NSCs. This effect was associated with significant changes in cell cycle-related proteins and may be regulated by calcium. Interestingly, calpain 1 and calpain 2 were found to play distinct roles in NSC fate decision. Calpain 1 expression levels were higher in self-renewing NSC and decreased with differentiation, while calpain 2 increased throughout differentiation. In addition, calpain 1 silencing resulted in increased levels of both neuronal and glial markers, β-III Tubulin and glial fibrillary acidic protein (GFAP. Calpain 2 silencing elicited decreased levels of GFAP. These results support a role for calpain 1 in repressing differentiation, thus maintaining a proliferative NSC pool, and suggest that calpain 2 is involved in glial differentiation.

Addressing the complexity of water chemistry in environmental fate modeling for engineered nanoparticles.

Science.gov (United States)

Sani-Kast, Nicole; Scheringer, Martin; Slomberg, Danielle; Labille, Jérôme; Praetorius, Antonia; Ollivier, Patrick; Hungerbühler, Konrad

2015-12-01

Engineered nanoparticle (ENP) fate models developed to date - aimed at predicting ENP concentration in the aqueous environment - have limited applicability because they employ constant environmental conditions along the modeled system or a highly specific environmental representation; both approaches do not show the effects of spatial and/or temporal variability. To address this conceptual gap, we developed a novel modeling strategy that: 1) incorporates spatial variability in environmental conditions in an existing ENP fate model; and 2) analyzes the effect of a wide range of randomly sampled environmental conditions (representing variations in water chemistry). This approach was employed to investigate the transport of nano-TiO2 in the Lower Rhône River (France) under numerous sets of environmental conditions. The predicted spatial concentration profiles of nano-TiO2 were then grouped according to their similarity by using cluster analysis. The analysis resulted in a small number of clusters representing groups of spatial concentration profiles. All clusters show nano-TiO2 accumulation in the sediment layer, supporting results from previous studies. Analysis of the characteristic features of each cluster demonstrated a strong association between the water conditions in regions close to the ENP emission source and the cluster membership of the corresponding spatial concentration profiles. In particular, water compositions favoring heteroaggregation between the ENPs and suspended particulate matter resulted in clusters of low variability. These conditions are, therefore, reliable predictors of the eventual fate of the modeled ENPs. The conclusions from this study are also valid for ENP fate in other large river systems. Our results, therefore, shift the focus of future modeling and experimental research of ENP environmental fate to the water characteristic in regions near the expected ENP emission sources. Under conditions favoring heteroaggregation in these

The environmental fate of polybrominated diphenyl ethers in the Great Lakes Basin

Science.gov (United States)

Gouin, Todd William

Semi-volatile organic compounds, such as the polybrominated diphenyl ethers (PBDEs) have the potential to undergo long-range atmospheric transport (LRAT) to remote locations, which can increase the exposure of sensitive ecosystems to potentially harmful substances. Regulatory instruments, such as the Stockholm Convention on persistent organic pollutants (POPs), have been implemented to limit and/or prevent this exposure. Through the acquisition of scientific data, knowledge can be gained about the environmental fate and human exposure of chemical substances, and the risks associated with using those substances assessed. PBDEs are a class of flame retardants that are used in a wide range of commercial products. In response to growing concern over the detection of PBDEs in remote regions, a number of regulatory bodies have implemented measures to restrict the use of PBDEs. Using a suite of environmental fate models it is shown that PBDEs will most likely partition to organic carbon in soil and sediment, and that their persistence in the environment will be strongly influenced by their reactivity in those compartments. The transport potential of the PBDEs is investigated using the transport and persistence level III model TaPL3, using model environments with and without vegetation. It is suggested that the LRAT potential of the PBDEs is likely to be greater for the more volatile lower brominated congeners than for the higher brominated congeners, and that the LRAT may be sensitive to seasonal changes in the environment, such as temperature, vegetation and changes in precipitation. Furthermore, model results suggest that the PBDEs may be subject to a "spring pulse" effect, whereby concentrations are elevated in air during the early spring. Field studies support the theory of a "spring pulse" effect, where concentrations were observed to be five times greater during the period between snowmelt and bud burst than the average concentration before and after, but conclude

BETR Global - A geographically explicit global-scale multimedia contaminant fate model

Energy Technology Data Exchange (ETDEWEB)

Macleod, M.; Waldow, H. von; Tay, P.; Armitage, J. M.; Wohrnschimmel, H.; Riley, W.; McKone, T. E.; Hungerbuhler, K.

2011-04-01

We present two new software implementations of the BETR Global multimedia contaminant fate model. The model uses steady-state or non-steady-state mass-balance calculations to describe the fate and transport of persistent organic pollutants using a desktop computer. The global environment is described using a database of long-term average monthly conditions on a 15{sup o} x 15{sup o} grid. We demonstrate BETR Global by modeling the global sources, transport, and removal of decamethylcyclopentasiloxane (D5).

Neural Correlates of Irritability in Disruptive Mood Dysregulation and Bipolar Disorders.

Science.gov (United States)

Wiggins, Jillian Lee; Brotman, Melissa A; Adleman, Nancy E; Kim, Pilyoung; Oakes, Allison H; Reynolds, Richard C; Chen, Gang; Pine, Daniel S; Leibenluft, Ellen

2016-07-01

Bipolar disorder and disruptive mood dysregulation disorder (DMDD) are clinically and pathophysiologically distinct, yet irritability can be a clinical feature of both illnesses. The authors examine whether the neural mechanisms mediating irritability differ between bipolar disorder and DMDD, using a face emotion labeling paradigm because such labeling is deficient in both patient groups. The authors hypothesized that during face emotion labeling, irritability would be associated with dysfunctional activation in the amygdala and other temporal and prefrontal regions in both disorders, but that the nature of these associations would differ between DMDD and bipolar disorder. During functional MRI acquisition, 71 youths (25 with DMDD, 24 with bipolar disorder, and 22 healthy youths) performed a labeling task with happy, fearful, and angry faces of varying emotional intensity. Participants with DMDD and bipolar disorder showed similar levels of irritability and did not differ from each other or from healthy youths in face emotion labeling accuracy. Irritability correlated with amygdala activity across all intensities for all emotions in the DMDD group; such correlation was present in the bipolar disorder group only for fearful faces. In the ventral visual stream, associations between neural activity and irritability were found more consistently in the DMDD group than in the bipolar disorder group, especially in response to ambiguous angry faces. These results suggest diagnostic specificity in the neural correlates of irritability, a symptom of both DMDD and bipolar disorder. Such evidence of distinct neural correlates suggests the need to evaluate different approaches to treating irritability in the two disorders.

Heterogeneous fates and dynamic rearrangement of regenerative epidermis-derived cells during zebrafish fin regeneration.

Science.gov (United States)

Shibata, Eri; Ando, Kazunori; Murase, Emiko; Kawakami, Atsushi

2018-04-13

The regenerative epidermis (RE) is a specialized tissue that plays an essential role in tissue regeneration. However, the fate of the RE during and after regeneration is unknown. In this study, we performed Cre- loxP -mediated cell fate tracking and revealed the fates of a major population of the RE cells that express fibronectin 1b ( fn1b ) during zebrafish fin regeneration. Our study showed that these RE cells are mainly recruited from the inter-ray epidermis, and that they follow heterogeneous cell fates. Early recruited cells contribute to initial wound healing and soon disappear by apoptosis, while the later recruited cells contribute to the regenerated epidermis. Intriguingly, many of these cells are also expelled from the regenerated tissue by a dynamic caudal movement of the epidermis over time, and in turn the loss of epidermal cells is replenished by a global self-replication of basal and suprabasal cells in fin. De-differentiation of non-basal epidermal cells into the basal epidermal cells did not occur during regeneration. Overall, our study reveals the heterogeneous fates of RE cells and a dynamic rearrangement of the epidermis during and after regeneration. © 2018. Published by The Company of Biologists Ltd.

Mergers and Acquisitions

OpenAIRE

Frasch, Manfred; Leptin, Maria

2000-01-01

Mergers and acquisitions (M&As) are booming a strategy of choice for organizations attempting to maintain a competitive advantage. Previous research on mergers and acquisitions declares that acquirers do not normally benefit from acquisitions. Targets, on the other hand, have a tendency of gaining positive returns in the few days surrounding merger announcements due to several characteristic on the acquisitions deal. The announcement period wealth effect on acquiring firms, however, is as cle...

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.

Myrmecochory and short-term seed fate in Rhamnus alaternus: Ant species and seed characteristics

Science.gov (United States)

Bas, J. M.; Oliveras, J.; Gómez, C.

2009-05-01

Benefits conferred on plants in ant-mediated seed dispersal mutualisms (myrmecochory) depend on the fate of transported seeds. We studied the effects of elaiosome presence, seed size and seed treatment (with and without passage through a bird's digestive tract) on short-term seed fate in Rhamnus alaternus. In our study, we define short-term seed, or initial, seed fate, as the location where ants release the seeds after ant contact with it. The elaiosomes had the most influence on short-term fate, i.e. whether or not seeds were transported to the nest. The workers usually transported big seeds more often than small ones, but small ants did not transport large seeds. Effect of seed size on transport depended on the ant species and on the treatment of the seed (manual extraction simulating a direct fall from the parent plant vs. bird deposition corresponding to preliminary primary dispersal). Probability of removal of elaiosome-bearing seeds to the nest by Aphaenogaster senilis increased with increasing seed weight.

Use of Artificial Neural Networks for Prediction of Convective Heat Transfer in Evaporative Units

Directory of Open Access Journals (Sweden)

Romero-Méndez Ricardo

2014-01-01

Full Text Available Convective heat transfer prediction of evaporative processes is more complicated than the heat transfer prediction of single-phase convective processes. This is due to the fact that physical phenomena involved in evaporative processes are very complex and vary with the vapor quality that increases gradually as more fluid is evaporated. Power-law correlations used for prediction of evaporative convection have proved little accuracy when used in practical cases. In this investigation, neural-network-based models have been used as a tool for prediction of the thermal performance of evaporative units. For this purpose, experimental data were obtained in a facility that includes a counter-flow concentric pipes heat exchanger with R134a refrigerant flowing inside the circular section and temperature controlled warm water moving through the annular section. This work also included the construction of an inverse Rankine refrigeration cycle that was equipped with measurement devices, sensors and a data acquisition system to collect the experimental measurements under different operating conditions. Part of the data were used to train several neural-network configurations. The best neural-network model was then used for prediction purposes and the results obtained were compared with experimental data not used for training purposes. The results obtained in this investigation reveal the convenience of using artificial neural networks as accurate predictive tools for determining convective heat transfer rates of evaporative processes.

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

Engineering the human pluripotent stem cell microenvironment to direct cell fate.

Science.gov (United States)

Hazeltine, Laurie B; Selekman, Joshua A; Palecek, Sean P

2013-11-15

Human pluripotent stem cells (hPSCs), including both embryonic stem cells and induced pluripotent stem cells, offer a potential cell source for research, drug screening, and regenerative medicine applications due to their unique ability to self-renew or differentiate to any somatic cell type. Before the full potential of hPSCs can be realized, robust protocols must be developed to direct their fate. Cell fate decisions are based on components of the surrounding microenvironment, including soluble factors, substrate or extracellular matrix, cell-cell interactions, mechanical forces, and 2D or 3D architecture. Depending on their spatio-temporal context, these components can signal hPSCs to either self-renew or differentiate to cell types of the ectoderm, mesoderm, or endoderm. Researchers working at the interface of engineering and biology have identified various factors which can affect hPSC fate, often based on lessons from embryonic development, and they have utilized this information to design in vitro niches which can reproducibly direct hPSC fate. This review highlights culture systems that have been engineered to promote self-renewal or differentiation of hPSCs, with a focus on studies that have elucidated the contributions of specific microenvironmental cues in the context of those culture systems. We propose the use of microsystem technologies for high-throughput screening of spatial-temporal presentation of cues, as this has been demonstrated to be a powerful approach for differentiating hPSCs to desired cell types. Copyright © 2013 Elsevier Inc. All rights reserved.

Meta-modeling of the pesticide fate model MACRO for groundwater exposure assessments using artificial neural networks

Science.gov (United States)

Stenemo, Fredrik; Lindahl, Anna M. L.; Gärdenäs, Annemieke; Jarvis, Nicholas

2007-08-01

Several simple index methods that use easily accessible data have been developed and included in decision-support systems to estimate pesticide leaching across larger areas. However, these methods often lack important process descriptions (e.g. macropore flow), which brings into question their reliability. Descriptions of macropore flow have been included in simulation models, but these are too complex and demanding for spatial applications. To resolve this dilemma, a neural network simulation meta-model of the dual-permeability macropore flow model MACRO was created for pesticide groundwater exposure assessment. The model was parameterized using pedotransfer functions that require as input the clay and sand content of the topsoil and subsoil, and the topsoil organic carbon content. The meta-model also requires the topsoil pesticide half-life and the soil organic carbon sorption coefficient as input. A fully connected feed-forward multilayer perceptron classification network with two hidden layers, linked to fully connected feed-forward multilayer perceptron neural networks with one hidden layer, trained on sub-sets of the target variable, was shown to be a suitable meta-model for the intended purpose. A Fourier amplitude sensitivity test showed that the model output (the 80th percentile average yearly pesticide concentration at 1 m depth for a 20 year simulation period) was sensitive to all input parameters. The two input parameters related to pesticide characteristics (i.e. soil organic carbon sorption coefficient and topsoil pesticide half-life) were the most influential, but texture in the topsoil was also quite important since it was assumed to control the mass exchange coefficient that regulates the strength of macropore flow. This is in contrast to models based on the advection-dispersion equation where soil texture is relatively unimportant. The use of the meta-model is exemplified with a case-study where the spatial variability of pesticide leaching is

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

THE FATE OF THE COMPACT REMNANT IN NEUTRON STAR MERGERS

Energy Technology Data Exchange (ETDEWEB)

Fryer, Chris L. [Department of Physics, The University of Arizona, Tucson, AZ 85721 (United States); Belczynski, Krzysztoff [Astronomical Observatory, University of Warsaw, Al Ujazdowskie 4, 00-478 Warsaw (Poland); Ramirez-Ruiz, Enrico [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Rosswog, Stephan [The Oskar klein Center, Department of Astronomy, AlbaNova, Stockholm University, SE-106 91 Stockholm (Sweden); Shen, Gang [Institute for Nuclear Theory, University of Washington, Seattle, WA 98195 (United States); Steiner, Andrew W. [Department of Physics and Astronomy, University of Tennessee, Knoxville, TN 37996 (United States)

2015-10-10

Neutron star (binary neutron star and neutron star–black hole) mergers are believed to produce short-duration gamma-ray bursts (GRBs). They are also believed to be the dominant source of gravitational waves to be detected by the advanced LIGO and advanced VIRGO and the dominant source of the heavy r-process elements in the universe. Whether or not these mergers produce short-duration GRBs depends sensitively on the fate of the core of the remnant (whether, and how quickly, it forms a black hole). In this paper, we combine the results of Newtonian merger calculations and equation of state studies to determine the fate of the cores of neutron star mergers. Using population studies, we can determine the distribution of these fates to compare to observations. We find that black hole cores form quickly only for equations of state that predict maximum non-rotating neutron star masses below 2.3–2.4 solar masses. If quick black hole formation is essential in producing GRBs, LIGO/Virgo observed rates compared to GRB rates could be used to constrain the equation of state for dense nuclear matter.

Mergers and Acquisitions

DEFF Research Database (Denmark)

Risberg, Annette

Introduction to the study of mergers and acquisitions. This book provides an understanding of the mergers and acquisitions process, how and why they occur, and also the broader implications for organizations. It presents issues including motives and planning, partner selection, integration......, employee experiences and communication. Mergers and acquisitions remain one of the most common forms of growth, yet they present considerable challenges for the companies and management involved. The effects on stakeholders, including shareholders, managers and employees, must be considered as well...... by editorial commentaries and reflects the important organizational and behavioural aspects which have often been ignored in the past. By providing this in-depth understanding of the mergers and acquisitions process, the reader understands not only how and why mergers and acquisitions occur, but also...

Choose your destiny: Make a cell fate decision with COUP-TFII.

Science.gov (United States)

Wu, San-Pin; Yu, Cheng-Tai; Tsai, Sophia Y; Tsai, Ming-Jer

2016-03-01

Cell fate specification is a critical process to generate cells with a wide range of characteristics from stem and progenitor cells. Emerging evidence demonstrates that the orphan nuclear receptor COUP-TFII serves as a key regulator in determining the cell identity during embryonic development. The present review summarizes our current knowledge on molecular mechanisms by which COUP-TFII employs to define the cell fates, with special emphasis on cardiovascular and renal systems. These novel insights pave the road for future studies of regenerative medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Detection of Pistachio Aflatoxin Using Raman Spectroscopy and Artificial Neural Networks

Directory of Open Access Journals (Sweden)

R Mohammadigol

2015-03-01

Full Text Available Pistachio contamination to aflatoxin has been known as a serious problem for pistachio exportation. With regards to the increasing demand for Raman spectroscopy to detect and classify different materials and also the current experimental and technical problems for measuring toxin (such as being expensive and time-consuming, the main objective of this study was to detect aflatoxin contamination in pistachio by using Raman spectroscopy technique and artificial neural networks. Three sets of samples were prepared: non-contaminated (healthy and contaminated samples with 20 and 100 ppb of the total aflatoxins (B1+B2+G1+G2. After spectral acquisition, considering to the results, spectral data were normalized and then principal components (PCs were extracted to reduce the data dimensions. For classification of the samples spectra, an artificial neural network was used with a feed forward back propagation algorithm for 4 inputs and 3 neurons in hidden layer. Mean overall accuracy was achieved to be 98 percent; therefore, non-liner Raman spectra data modeling by ANN for samples classification was successful.

Ordered self-assembled monolayers terminated with different chemical functional groups direct neural stem cell linage behaviours

International Nuclear Information System (INIS)

Yao, Shenglian; Liu, Xi; He, Jin; Wang, Xiumei; Wang, Ying; Cui, Fu-Zhai

2016-01-01

Neural stem cells (NSCs) have been a promising candidate for stem cell-based nerve tissue regeneration. Therefore, the design of idea biomaterials that deliver precise regulatory signals to control stem cell fate is currently a crucial issue that depends on a profound understanding of the interactions between NSCs with the surrounding micro-environment. In this work, self-assembled monolayers of alkanethiols on gold with different chemical groups, including hydroxyl (−OH), amino (−NH 2 ), carboxyl (−COOH) and methyl (−CH 3 ), were used as a simple model to study the effects of surface chemistry on NSC fate decisions. Contact angle measurement and x-ray photoelectron spectroscopy (XPS) examination implied that all types of alkanethiols self-assembled on gold into a close-packed phase structure with similar molecular densities. In this study, we evaluated NSC adhesion, migration and differentiation in response to different chemical functional groups cultured under serum-free conditions. Our studies showed that NSCs exhibited certain phenotypes with extreme sensitivity to surface chemical groups. Compared with other functional groups, the SAMs with hydroxyl end-groups provided the best micro-environment in promoting NSC migration and maintaining an undifferentiated or neuronal differentiation state.  −NH 2 surfaces directed neural stem cells into astrocytic lineages, while NSCs on  −COOH and  −CH 3 surfaces had a similar potency to differentiate into three nerve lineages. To further investigate the possible signaling pathway, the gene expression of integrin β1 and β4 were examined. The results indicated that a high expression of β1 integrin would probably have a tight correlation with the expression of nestin, which implied the stemness of NSCs, while β4 integrin seemed to correspond to the differentiated NSCs. The results presented here give useful information for the future design of biomaterials to regulate the preservation

Selective neuronal differentiation of neural stem cells induced by nanosecond microplasma agitation.

Science.gov (United States)

Xiong, Z; Zhao, S; Mao, X; Lu, X; He, G; Yang, G; Chen, M; Ishaq, M; Ostrikov, K

2014-03-01

An essential step for therapeutic and research applications of stem cells is their ability to differentiate into specific cell types. Neuronal cells are of great interest for medical treatment of neurodegenerative diseases and traumatic injuries of central nervous system (CNS), but efforts to produce these cells have been met with only modest success. In an attempt of finding new approaches, atmospheric-pressure room-temperature microplasma jets (MPJs) are shown to effectively direct in vitro differentiation of neural stem cells (NSCs) predominantly into neuronal lineage. Murine neural stem cells (C17.2-NSCs) treated with MPJs exhibit rapid proliferation and differentiation with longer neurites and cell bodies eventually forming neuronal networks. MPJs regulate ~75% of NSCs to differentiate into neurons, which is a higher efficiency compared to common protein- and growth factors-based differentiation. NSCs exposure to quantized and transient (~150 ns) micro-plasma bullets up-regulates expression of different cell lineage markers as β-Tubulin III (for neurons) and O4 (for oligodendrocytes), while the expression of GFAP (for astrocytes) remains unchanged, as evidenced by quantitative PCR, immunofluorescence microscopy and Western Blot assay. It is shown that the plasma-increased nitric oxide (NO) production is a factor in the fate choice and differentiation of NSCs followed by axonal growth. The differentiated NSC cells matured and produced mostly cholinergic and motor neuronal progeny. It is also demonstrated that exposure of primary rat NSCs to the microplasma leads to quite similar differentiation effects. This suggests that the observed effect may potentially be generic and applicable to other types of neural progenitor cells. The application of this new in vitro strategy to selectively differentiate NSCs into neurons represents a step towards reproducible and efficient production of the desired NSC derivatives. Published by Elsevier B.V.

Selective neuronal differentiation of neural stem cells induced by nanosecond microplasma agitation

Directory of Open Access Journals (Sweden)

Z. Xiong

2014-03-01

Full Text Available An essential step for therapeutic and research applications of stem cells is their ability to differentiate into specific cell types. Neuronal cells are of great interest for medical treatment of neurodegenerative diseases and traumatic injuries of central nervous system (CNS, but efforts to produce these cells have been met with only modest success. In an attempt of finding new approaches, atmospheric-pressure room-temperature microplasma jets (MPJs are shown to effectively direct in vitro differentiation of neural stem cells (NSCs predominantly into neuronal lineage. Murine neural stem cells (C17.2-NSCs treated with MPJs exhibit rapid proliferation and differentiation with longer neurites and cell bodies eventually forming neuronal networks. MPJs regulate ~75% of NSCs to differentiate into neurons, which is a higher efficiency compared to common protein- and growth factors-based differentiation. NSCs exposure to quantized and transient (~150 ns micro-plasma bullets up-regulates expression of different cell lineage markers as β-Tubulin III (for neurons and O4 (for oligodendrocytes, while the expression of GFAP (for astrocytes remains unchanged, as evidenced by quantitative PCR, immunofluorescence microscopy and Western Blot assay. It is shown that the plasma-increased nitric oxide (NO production is a factor in the fate choice and differentiation of NSCs followed by axonal growth. The differentiated NSC cells matured and produced mostly cholinergic and motor neuronal progeny. It is also demonstrated that exposure of primary rat NSCs to the microplasma leads to quite similar differentiation effects. This suggests that the observed effect may potentially be generic and applicable to other types of neural progenitor cells. The application of this new in vitro strategy to selectively differentiate NSCs into neurons represents a step towards reproducible and efficient production of the desired NSC derivatives.

Organic contaminant transport and fate in the subsurface: evolution of knowledge and understanding

Science.gov (United States)

Essaid, Hedeff I.; Bekins, Barbara A.; Cozzarelli, Isabelle M.

2015-01-01

Toxic organic contaminants may enter the subsurface as slightly soluble and volatile nonaqueous phase liquids (NAPLs) or as dissolved solutes resulting in contaminant plumes emanating from the source zone. A large body of research published in Water Resources Research has been devoted to characterizing and understanding processes controlling the transport and fate of these organic contaminants and the effectiveness of natural attenuation, bioremediation, and other remedial technologies. These contributions include studies of NAPL flow, entrapment, and interphase mass transfer that have advanced from the analysis of simple systems with uniform properties and equilibrium contaminant phase partitioning to complex systems with pore-scale and macroscale heterogeneity and rate-limited interphase mass transfer. Understanding of the fate of dissolved organic plumes has advanced from when biodegradation was thought to require oxygen to recognition of the importance of anaerobic biodegradation, multiple redox zones, microbial enzyme kinetics, and mixing of organic contaminants and electron acceptors at plume fringes. Challenges remain in understanding the impacts of physical, chemical, biological, and hydrogeological heterogeneity, pore-scale interactions, and mixing on the fate of organic contaminants. Further effort is needed to successfully incorporate these processes into field-scale predictions of transport and fate. Regulations have greatly reduced the frequency of new point-source contamination problems; however, remediation at many legacy plumes remains challenging. A number of fields of current relevance are benefiting from research advances from point-source contaminant research. These include geologic carbon sequestration, nonpoint-source contamination, aquifer storage and recovery, the fate of contaminants from oil and gas development, and enhanced bioremediation.

Social Behavior in Medulloblastoma: Functional Analysis of Tumor-Supporting Glial Cells

Science.gov (United States)

2015-10-01

the manuscript with inputs from all authors. All authors reviewed the manuscript. Acknowledgements We thank Chris Doe, David Rowitch, and Praveen...201–208. Goodrich, L.V., Milenković, L., Higgins , K.M., and Scott, M.P. (1997). Altered Neural Cell Fates and Medulloblastoma in Mouse patched...Genes & Development 27, 98–115. Goodrich, L.V., Milenković, L., Higgins , K.M., and Scott, M.P. (1997). Altered Neural Cell Fates and Medulloblastoma in

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.

Plasmid-based generation of induced neural stem cells from adult human fibroblasts

Directory of Open Access Journals (Sweden)

Philipp Capetian

2016-10-01

Full Text Available Direct reprogramming from somatic to neural cell types has become an alternative to induced pluripotent stem cells. Most protocols employ viral expression systems, posing the risk of random genomic integration. Recent developments led to plasmid-based protocols, lowering this risk. However, these protocols either relied on continuous presence of a variety of small molecules or were only able to reprogram murine cells. We therefore established a reprogramming protocol based on vectors containing the Epstein-Barr virus (EBV-derived oriP/EBNA1 as well as the defined expression factors Oct3/4, Sox2, Klf4, L-myc, Lin28, and a small hairpin directed against p53. We employed a defined neural medium in combination with the neurotrophins bFGF, EGF and FGF4 for cultivation without the addition of small molecules. After reprogramming, cells demonstrated a temporary increase in the expression of endogenous Oct3/4. We obtained induced neural stem cells (iNSC 30 days after transfection. In contrast to previous results, plasmid vectors as well as a residual expression of reprogramming factors remained detectable in all cell lines. Cells showed a robust differentiation into neuronal (72% and glial cells (9% astrocytes, 6% oligodendrocytes. Despite the temporary increase of pluripotency-associated Oct3/4 expression during reprogramming, we did not detect pluripotent stem cells or non-neural cells in culture (except occasional residual fibroblasts. Neurons showed electrical activity and functional glutamatergic synapses. Our results demonstrate that reprogramming adult human fibroblasts to iNSC by plasmid vectors and basic neural medium without small molecules is possible and feasible. However, a full set of pluripotency-associated transcription factors may indeed result in the acquisition of a transient (at least partial pluripotent intermediate during reprogramming. In contrast to previous reports, the EBV-based plasmid system remained present and active inside

Fate in the religion of the Lepchas

Directory of Open Access Journals (Sweden)

Halfdan Siiger

1967-02-01

Full Text Available The Lepchas are mountainous agriculturalists who live in the State of Sikkim in the Himalayas and in some adjacent Indian districts. To the Lepchas the supernatural world is divided into two groups, the rum, or the mainly benevolent supernatural beings, and the mung, or the malignant supernatural beings. Any evil occurrence is in the first instance ascribed to the malignant activities of the mung, but it may, under certain conditions, also be due to temporary on the part of some or other rum. If it is obvious that the evil occurrence is caused by a human being, this person is considered to be governed by some mung, or he may, which is much worse, be a mung in human disguise. At all events, any evil occurrence is experienced as the result of the evil will-power of some or other malignant supernatural being. Consequently, we cannot apply our technical term "Fate" to such occurrences, and Fate as an abstract concept cannot be used, when we speak of the Lepchas.

Fate of triazoles in softwood upon environmental exposure.

Science.gov (United States)

Kukowski, Klara; Martinská, Veronika; Sedgeman, Carl A; Kuplic, Paige; Kozliak, Evguenii I; Fisher, Stephen; Kubátová, Alena

2017-10-01

Determining the fate of preservatives in commercial wood products is essential to minimize their losses and improve protective impregnation techniques. The fate of triazole fungicides in ponderosa pine wood was investigated in both outdoor and controlled-environment experiments using a representative triazole, tebuconazole (TAZ), which was accompanied by propiconazole (PAZ) in selected experiments. The study was designed to mimic industrial settings used in window frame manufacturing. To investigate the TAZ fate in detail, loosely and strongly bound fractions were differentiated using a multi-step extraction. The loosely bound TAZ fraction extracted through two sonications accounted for 85± 5% of the total TAZ, while the strongly bound TAZ was extracted only with an exhaustive Soxhlet extraction and corresponded to the remaining 15± 5%. A significant fraction (∼80%) of the original TAZ remained in the wood despite a six-month exposure to harsh environmental conditions, maintaining wood preservation and assuring minimal environmental impact. Depletion of loosely bound TAZ was observed from cross-sectional surfaces when exposed to rain, high humidity and sunlight. Water leaching was deemed to be the major route leading to triazole losses from wood. Leaching rate was found to be slightly higher for TAZ than for PAZ. The contribution of bio-, photo- and thermal degradation of triazoles was negligible as both PAZ and TAZ sorbed in wood remained intact. Triazole evaporation was also found to be minor at the moderate temperature (20-25 °C) recorded throughout the outdoor study. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fate and behaviour of phenanthrene in the natural and artificial soils

International Nuclear Information System (INIS)

Hofman, Jakub; Rhodes, Angela; Semple, Kirk T.

2008-01-01

OECD artificial soil has been used routinely as a standardized substrate for soil toxicity tests. However, can be the fate, behaviour and effects of contaminants in artificial soil extrapolated to natural soils? The aim of our study was to verify this hypothesis by comparing the loss, extraction, and bioavailability of phenanthrene in three artificial and three natural soils of comparable organic carbon content. Soils were spiked with 14 C-phenanthrene and total 14 C-activity change, the fractions extracted by dichloromethane, 70% ethanol, and hydroxypropyl-β-cyclodextrin, the fraction mineralized by Pseudomonas sp., and taken up by Enchytraeus albidus were measured after 1, 14, 42, and 84 d aging. The loss, extraction, biodegradation and uptake were several times lower in the artificial than natural soils and these differences increased with increasing soil-phenanthrene contact time. These results imply that artificial soil should be used cautiously for the prediction of fate and behaviour in natural soils. - Artificial soils show substantially different fate and behaviour of phenanthrene than natural soils, which cannot be easily extrapolated or modelled

Fate of enniatins and deoxynivalenol during pasta cooking

NARCIS (Netherlands)

Nijs, de Monique; Top, van den Hester; Stoppelaar, de Joyce; Lopez Sanchez, Patricia; Mol, Hans

2016-01-01

The fate of deoxynivalenol and enniatins was studied during cooking of commercially available dry pasta in the Netherlands in 2014. Five samples containing relatively high levels of deoxynivalenol and/or enniatins were selected for the cooking experiment. Cooking was performed in duplicate on

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

Modeling Engineered Nanomaterials (ENMs) Fate and ...

Science.gov (United States)

Under the Toxic Substances Control Act (TSCA), the Environmental Protection Agency (EPA) is required to perform new chemical reviews of engineered nanomaterials (ENMs) identified in pre-manufacture notices. However, environmental fate models developed for traditional contaminants are limited in their ability to simulate the environmental behavior of nanomaterials due to incomplete understanding and representation of the processes governing nanomaterial distribution in the environment and by scarce empirical data quantifying the interaction of nanomaterials with environmental surfaces. We have updated the Water Quality Analysis Simulation Program (WASP), version S, to incorporate nanomaterials as an explicitly simulated state variable. WASPS now has the capability to simulate nanomaterial fate and transport in surface waters and sediments using heteroaggregation, the kinetic process governing the attachment of nanomaterials to particles and subsequently ENM distribution in the aqueous and sediment phases. Unlike dissolved chemicals which use equilibrium partition coefficients, heteroaggregation consists of a particle collision rate and an attachment efficiency ( lXhet) that generally acts as a one direction process. To demonstrate, we used a derived a het value from sediment attachment studies to parameterize WASP for simulation of multi walled carbon nanotube (MWCNT) transport in Brier Creek, a coastal plain river located in central eastern Georgia, USA and a tr

Fate of Fusarium Toxins during Brewing.

Science.gov (United States)

Habler, Katharina; Geissinger, Cajetan; Hofer, Katharina; Schüler, Jan; Moghari, Sarah; Hess, Michael; Gastl, Martina; Rychlik, Michael

2017-01-11

Some information is available about the fate of Fusarium toxins during the brewing process, but only little is known about the single processing steps in detail. In our study we produced beer from two different barley cultivars inoculated with three different Fusarium species, namely, Fusarium culmorum, Fusarium sporotrichioides, and Fusarium avenaceum, producing a wide range of mycotoxins such as type B trichothecenes, type A trichothecenes, and enniatins. By the use of multi-mycotoxin LC-MS/MS stable isotope dilution methods we were able to follow the fate of Fusarium toxins during the entire brewing process. In particular, the type B trichothecenes deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol showed similar behaviors. Between 35 and 52% of those toxins remained in the beer after filtration. The contents of the potentially hazardous deoxynivalenol-3-glucoside and the type A trichothecenes increased during mashing, but a rapid decrease of deoxynivalenol-3-glucoside content was found during the following steps of lautering and wort boiling. The concentration of enniatins greatly decreased with the discarding of spent grains or finally with the hot break. The results of our study show the retention of diverse Fusarium toxins during the brewing process and allow for assessing the food safety of beer regarding the monitored Fusarium mycotoxins.

Human mammary progenitor cell fate decisions are productsof interactions with combinatorial microenvironments

DEFF Research Database (Denmark)

LaBarge, Mark A.; Nelson, Celeste M.; Villadsen, René

2009-01-01

factors, ECM, and other cells, as well as physical properties of the ECM. To understand regulation of fate decisions, therefore, would require a means of understanding carefully choreographed combinatorial interactions. Here we used microenvironment protein microarrays to functionally identify...... combinations of cell-extrinsic mammary gland proteins and ECM molecules that imposed specific cell fates on bipotent human mammary progenitor cells.Micropatterned cell culture surfaces were fabricated to distinguish between the instructive effects of cell-cell versus cell-ECM interactions, as well...

Pluripotency factors in embryonic stem cells regulate differentiation into germ layers.

Science.gov (United States)

Thomson, Matt; Liu, Siyuan John; Zou, Ling-Nan; Smith, Zack; Meissner, Alexander; Ramanathan, Sharad

2011-06-10

Cell fate decisions are fundamental for development, but we do not know how transcriptional networks reorganize during the transition from a pluripotent to a differentiated cell state. Here, we asked how mouse embryonic stem cells (ESCs) leave the pluripotent state and choose between germ layer fates. By analyzing the dynamics of the transcriptional circuit that maintains pluripotency, we found that Oct4 and Sox2, proteins that maintain ESC identity, also orchestrate germ layer fate selection. Oct4 suppresses neural ectodermal differentiation and promotes mesendodermal differentiation; Sox2 inhibits mesendodermal differentiation and promotes neural ectodermal differentiation. Differentiation signals continuously and asymmetrically modulate Oct4 and Sox2 protein levels, altering their binding pattern in the genome, and leading to cell fate choice. The same factors that maintain pluripotency thus also integrate external signals and control lineage selection. Our study provides a framework for understanding how complex transcription factor networks control cell fate decisions in progenitor cells. Copyright © 2011 Elsevier Inc. All rights reserved.

Polylox barcoding reveals haematopoietic stem cell fates realized in vivo

Science.gov (United States)

Rössler, Jens; Wang, Xi; Postrach, Daniel; Busch, Katrin; Rode, Immanuel; Klapproth, Kay; Dietlein, Nikolaus; Quedenau, Claudia; Chen, Wei; Sauer, Sascha; Wolf, Stephan; Höfer, Thomas; Rodewald, Hans-Reimer

2017-01-01

Developmental deconvolution of complex organs and tissues at the level of individual cells remains challenging. Non-invasive genetic fate mapping1 has been widely used, but the low number of distinct fluorescent marker proteins limits its resolution. Much higher numbers of cell markers have been generated using viral integration sites2, viral barcodes3, and strategies based on transposons4 and CRISPR/Cas9 genome editing5; however, temporal and tissue-specific induction of barcodes in situ has not been achieved. Here we report the development of an artificial DNA recombination locus (termed Polylox) that enables broadly applicable endogenous barcoding based on the Cre-loxP recombination system6,7. Polylox recombination in situ reaches a practical diversity of several hundred thousand barcodes, allowing tagging of single cells. We have used this experimental system, combined with fate mapping, to assess haematopoietic stem cell (HSC) fates in vivo. Classical models of haematopoietic lineage specification assume a tree with few major branches. More recently, driven in part by the development of more efficient single-cell assays and improved transplantation efficiencies, different models have been proposed, in which unilineage priming may occur in mice and humans at the level of HSCs8–10. We have introduced barcodes into HSC progenitors in embryonic mice, and found that the adult HSC compartment is a mosaic of embryo-derived HSC clones, some of which are unexpectedly large. Most HSC clones gave rise to multilineage or oligolineage fates, arguing against unilineage priming, and suggesting coherent usage of the potential of cells in a clone. The spreading of barcodes, both after induction in embryos and in adult mice, revealed a basic split between common myeloid-erythroid development and common lymphocyte development, supporting the long-held but contested view of a tree-like haematopoietic structure. PMID:28813413

Polylox barcoding reveals haematopoietic stem cell fates realized in vivo.

Science.gov (United States)

Pei, Weike; Feyerabend, Thorsten B; Rössler, Jens; Wang, Xi; Postrach, Daniel; Busch, Katrin; Rode, Immanuel; Klapproth, Kay; Dietlein, Nikolaus; Quedenau, Claudia; Chen, Wei; Sauer, Sascha; Wolf, Stephan; Höfer, Thomas; Rodewald, Hans-Reimer

2017-08-24

Developmental deconvolution of complex organs and tissues at the level of individual cells remains challenging. Non-invasive genetic fate mapping has been widely used, but the low number of distinct fluorescent marker proteins limits its resolution. Much higher numbers of cell markers have been generated using viral integration sites, viral barcodes, and strategies based on transposons and CRISPR-Cas9 genome editing; however, temporal and tissue-specific induction of barcodes in situ has not been achieved. Here we report the development of an artificial DNA recombination locus (termed Polylox) that enables broadly applicable endogenous barcoding based on the Cre-loxP recombination system. Polylox recombination in situ reaches a practical diversity of several hundred thousand barcodes, allowing tagging of single cells. We have used this experimental system, combined with fate mapping, to assess haematopoietic stem cell (HSC) fates in vivo. Classical models of haematopoietic lineage specification assume a tree with few major branches. More recently, driven in part by the development of more efficient single-cell assays and improved transplantation efficiencies, different models have been proposed, in which unilineage priming may occur in mice and humans at the level of HSCs. We have introduced barcodes into HSC progenitors in embryonic mice, and found that the adult HSC compartment is a mosaic of embryo-derived HSC clones, some of which are unexpectedly large. Most HSC clones gave rise to multilineage or oligolineage fates, arguing against unilineage priming, and suggesting coherent usage of the potential of cells in a clone. The spreading of barcodes, both after induction in embryos and in adult mice, revealed a basic split between common myeloid-erythroid development and common lymphocyte development, supporting the long-held but contested view of a tree-like haematopoietic structure.

Controlling destiny through chemistry: small-molecule regulators of cell fate.

Science.gov (United States)

Firestone, Ari J; Chen, James K

2010-01-15

Controlling cell fate is essential for embryonic development, tissue regeneration, and the prevention of human disease. With each cell in the human body sharing a common genome, achieving the appropriate spectrum of stem cells and their differentiated lineages requires the selective activation of developmental signaling pathways, the expression of specific target genes, and the maintenance of these cellular states through epigenetic mechanisms. Small molecules that target these regulatory processes are therefore valuable tools for probing and manipulating the molecular mechanisms by which stem cells self-renew, differentiate, and arise from somatic cell reprogramming. Pharmacological modulators of cell fate could also help remediate human diseases caused by dysregulated cell proliferation or differentiation, heralding a new era in molecular therapeutics.

2017 NAIP Acquisition Map

Data.gov (United States)

Farm Service Agency, Department of Agriculture — Planned States for 2017 NAIP acquisition and acquisition status layer (updated daily). Updates to the acquisition seasons may be made during the season to...

Fate of macrosarcocyst of Sarcocystis gigantea in sheep

Directory of Open Access Journals (Sweden)

N. S. Al-Hyali1, E. R. Kennany2 and L.Y. Khalil1

2011-01-01

Full Text Available This study was conducted to detect the fate of macrosarcocysts of Sarcocystis gigantea in the tongue and eosophagus of naturally infected sheep, via collection of 25 samples, 10 of which showed calcification. The results showed presence of white different size grains on the wall of the pale eosophagus, in addition to presence of nodules containing white chalky materials and on cutting by knife produced grunting sound which indicated calcification. Histopathological results showed presence of granulomatous nodules that contained necrotic centers infiltration by inflammatory cells. Some of which were free from zoites in addition to presence of calcium salt precipitation, which represented dystrophic calcification. Eosinophilic myositis appeared in the tongue was associated with ruptured cyst and released zoites in muscular tissue. Some histological sections revealed ruptured macrocystis with thin wall deposited between muscle bundles. In conclusion, this study showed that the fate of macrocysts included the formation of granulomatous nodules associated with dystrophic calcification and dead zoites in eosophagous more than that in the tongue.

Evaluating the fate of organic compounds in the Cameroon ...

African Journals Online (AJOL)

ISHIOMA

A level III fugacity model was developed to evaluate the fate of chemicals in the Cameroon ... environment, quantify intermedia transfer processes and the major loss ... perform baseline exposure and risk assessment of chemicals used in ...

Investigating the Toxicity and Environmental Fate of Graphene Nanomaterials

Science.gov (United States)

The Hersam Laboratory at Northwestern University works with the Center for Environmental Implications of Nanotechnology and the United States Environmental Protection Agency to study the toxicity and environmental fate of emergent nanomaterials, specifically carbon-based nanomate...

Study of the photodegradation of a fragrance ingredient for aquatic environmental fate assessment.

Science.gov (United States)

Lin, Jianming; Emberger, Matthew

2017-04-01

Photodegradation is an important abiotic degradation process to be taken into account for more accurate assessment of the fate of chemicals in the aquatic environment, especially those that are not readily biodegradable. Although the significant role of indirect photodegradation in the environmental fate of chemicals has been revealed in recent research, because of the many confounding factors affecting its kinetics, no straightforward approaches can be used to investigate this degradation process for environmental fate assessment. The indirect photodegradation of a fragrance ingredient named Pamplewood was studied in this work for its fate assessment. Indirect photodegradation rates under various indoor and outdoor conditions were measured by using an LC-MS method. Although the half-lives varied from 4 to 13 days, they collectively indicated that Pamplewood is intrinsically photolabile and can undergo rapid photodegradation. Results from quencher experiments revealed that ⋅OH was the main reactive intermediate responsible for indirect photodegradation, with a half-life of about 18 days in sunlit surface water, based on the experimentally determined second-order rate constant (8.48 ± 0.19 × 10 9  M -1  s -1 ). Photodegradation products of Pamplewood were also studied by GC-MS, LC-MS and total organic carbon content analyses. The results indicated that intermediates of Pamplewood photodegradation continued to photodegrade into smaller and more polar species. Complete mineralization of Pamplewood was observed when it was reacted with hydroxyl radicals in an aqueous solution. This novel approach can be applied for a more realistic environmental fate assessment of other non-readily biodegradable, hydrolysis-resistant, and non-sunlight-absorbing fragrance ingredients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Environmental fate of rice paddy pesticides in a model ecosystem.

Science.gov (United States)

Tomizawa, C; Kazano, H

1979-01-01

The distribution and metabolic fate of several rice paddy pesticides were evaluated in a modified model ecosystem. Among the three BHC isomers, beta-isomer was the most stable and bioconcentrated in all of the organisms. Alpha- and gamma-isomers were moderately persistent and degraded to some extent during the 33 day period. Disulfoton was relatively persistent due to the transformation to its oxidation products. Pyridaphenthion was fairly biodegradable. N-Phenyl maleic hydrazide derived from the hydrolysis of pyridaphenthion was not detected in the organisms though it was found in the aquarium water after 33 days. Cartap and edifenphos were considerably biodegradable, and the ratio of the conversion to water soluble metabolites was very high. There was a distinct difference in the persistence of Kitazin P and edifenphos in the aquarium water. It appeared that the hydrolysis rate of the pesticides affected their fate in the organisms. PCP appeared to be moderately biodegradable. CNP was considerably stable and stored in the organisms though the concentration in the aquarium water was relatively low. The persistence and distribution of the pesticides in the model ecosystem were dependent on their chemical structures. In spite of the limitation derived from short experimental period, the model ecosystem may be applicable for predicting the environmental fate of pesticides.

The level of the transcription factor Pax6 is essential for controlling the balance between neural stem cell self-renewal and neurogenesis.

Directory of Open Access Journals (Sweden)

Stephen N Sansom

2009-06-01

Full Text Available Neural stem cell self-renewal, neurogenesis, and cell fate determination are processes that control the generation of specific classes of neurons at the correct place and time. The transcription factor Pax6 is essential for neural stem cell proliferation, multipotency, and neurogenesis in many regions of the central nervous system, including the cerebral cortex. We used Pax6 as an entry point to define the cellular networks controlling neural stem cell self-renewal and neurogenesis in stem cells of the developing mouse cerebral cortex. We identified the genomic binding locations of Pax6 in neocortical stem cells during normal development and ascertained the functional significance of genes that we found to be regulated by Pax6, finding that Pax6 positively and directly regulates cohorts of genes that promote neural stem cell self-renewal, basal progenitor cell genesis, and neurogenesis. Notably, we defined a core network regulating neocortical stem cell decision-making in which Pax6 interacts with three other regulators of neurogenesis, Neurog2, Ascl1, and Hes1. Analyses of the biological function of Pax6 in neural stem cells through phenotypic analyses of Pax6 gain- and loss-of-function mutant cortices demonstrated that the Pax6-regulated networks operating in neural stem cells are highly dosage sensitive. Increasing Pax6 levels drives the system towards neurogenesis and basal progenitor cell genesis by increasing expression of a cohort of basal progenitor cell determinants, including the key transcription factor Eomes/Tbr2, and thus towards neurogenesis at the expense of self-renewal. Removing Pax6 reduces cortical stem cell self-renewal by decreasing expression of key cell cycle regulators, resulting in excess early neurogenesis. We find that the relative levels of Pax6, Hes1, and Neurog2 are key determinants of a dynamic network that controls whether neural stem cells self-renew, generate cortical neurons, or generate basal progenitor cells

Data acquisition

International Nuclear Information System (INIS)

Clout, P.N.

1982-01-01

Data acquisition systems are discussed for molecular biology experiments using synchrotron radiation sources. The data acquisition system requirements are considered. The components of the solution are described including hardwired solutions and computer-based solutions. Finally, the considerations for the choice of the computer-based solution are outlined. (U.K.)

THE FATE OF TANNINS IN CORSICAN PINE LITTER

NARCIS (Netherlands)

Nierop, K.G.J.; Verstraten, J.M.

2006-01-01

Tannins are ubiquitous in higher plants and therefore also in litter and soils where they affect many biogeochemical processes. Despite this well recognized role, the fate of tannins in litter and mineral soils is hardly known as often only trace amounts, if any, of tannins are measured. In this

Fate of 14C-labelled compounds in marine environment

International Nuclear Information System (INIS)

Kale, S.P.; Raghu, K.; Sherkhane, P.D.; Murthy, N.B.K.

1999-01-01

Model ecosystems have played an important role in predicting environmental behavior of agrochemicals. The microcosms used in these studies generally include soil units containing usual biotic components common for that ecosystem. In present studies, scope of two such ecosystems has been extended to study the fate of 14 C-labelled pesticides in marine environment. 14 C-labelled pesticides used in these studies were chlorpyrifos, DDT and HCH. Two systems were developed in laboratory simulating marine environment to study the fate of these pesticides. The first system was developed in an all glass aquarium tank with marine sediments, seawater, clams and algae and is referred to as marine ecosystem. The second system was developed to permit the total 14 C-mass balance studies. It contained marine sediments under moist (60% water holding capacity) or flooded conditions and it is referred to as continuous flow system. Fate of 14 C-DDT was studied in marine ecosystem while degradation of 14 C-chlorpyrifos and 14 C-HCH was studied in continuous flow system. 14 C-DDT did not bioaccumulate in clams while at the end of 60 days 50% of the applied 14 C-activity was present in sediment fraction of marine ecosystem. 14 C-HCH degradation showed about 22-26% mineralization while 45-55% of the applied activity was recovered as organic volatiles. No significant bound residues were formed. 14 C-chorpyrifos underwent considerable degradation in marine environment. TCP was the major degradation product. (author)

Environmental Behavior and Fate of Explosives in Groundwater from the Milan Army Ammunition Plant in Aquatic and Wetland Plants. Fate of TNT and RDX

National Research Council Canada - National Science Library

Best, Elly

1998-01-01

The present study was performed to elucidate the environmental behavior and fate of TNT and RDX in aquatic and wetland plants collected from a field-scale wetland demonstration deployed at Milan Army...

Data Acquisition System

International Nuclear Information System (INIS)

Cirstea, C.D.; Buda, S.I.; Constantin, F.

2005-01-01

This paper deals with a multi parametric acquisition system developed for a four input Analog to Digital Converter working in CAMAC Standard. The acquisition software is built in MS Visual C++ on a standard PC with a USB interface. It has a visual interface which permits Start/Stop of the acquisition, setting the type of acquisition (True/Live time), the time and various menus for primary data acquisition. The spectrum is dynamically visualized with a moving cursor indicating the content and position. The microcontroller PIC16C765 is used for data transfer from ADC to PC; The microcontroller and the software create an embedded system which emulates the CAMAC protocol programming the 4 input ADC for operating modes ('zero suppression', 'addressed' and 'sequential') and handling the data transfers from ADC to its internal memory. From its memory the data is transferred into the PC by the USB interface. The work is in progress. (authors)

Data acquisition system

International Nuclear Information System (INIS)

Cirstea, D.C.; Buda, S.I.; Constantin, F.

2005-01-01

The topic of this paper deals with a multi parametric acquisition system developed around a four input Analog to Digital Converter working in CAMAC Standard. The acquisition software is built in MS Visual C++ on a standard PC with a USB interface. It has a visual interface which permits Start/Stop of the acquisition, setting the type of acquisition (True/Live time), the time and various menus for primary data acquisition. The spectrum is dynamically visualized with a moving cursor indicating the content and position. The microcontroller PIC16C765 is used for data transfer from ADC to PC; The microcontroller and the software create an embedded system which emulates the CAMAC protocol programming, the 4 input ADC for operating modes ('zero suppression', 'addressed' and 'sequential') and handling the data transfers from ADC to its internal memory. From its memory the data is transferred into the PC by the USB interface. The work is in progress. (authors)

Pak2 Controls Acquisition of NKT Cell Fate by Regulating Expression of the Transcription Factors PLZF and Egr2

Science.gov (United States)

O’Hagan, Kyle L.; Zhao, Jie; Pryshchep, Olga; Wang, Chyung-Ru

2015-01-01

NKT cells constitute a small population of T cells developed in the thymus that produce large amounts of cytokines and chemokines in response to lipid Ags. Signaling through the Vα14-Jα18 TCR instructs commitment to the NKT cell lineage, but the precise signaling mechanisms that instruct their lineage choice are unclear. In this article, we report that the cytoskeletal remodeling protein, p21-activated kinase 2 (Pak2), was essential for NKT cell development. Loss of Pak2 in T cells reduced stage III NKT cells in the thymus and periphery. Among different NKT cell subsets, Pak2 was necessary for the generation and function of NKT1 and NKT2 cells, but not NKT17 cells. Mechanistically, expression of Egr2 and promyelocytic leukemia zinc finger (PLZF), two key transcription factors for acquiring the NKT cell fate, were markedly diminished in the absence of Pak2. Diminished expression of Egr2 and PLZF were not caused by aberrant TCR signaling, as determined using a Nur77-GFP reporter, but were likely due to impaired induction and maintenance of signaling lymphocyte activation molecule 6 expression, a TCR costimulatory receptor required for NKT cell development. These data suggest that Pak2 controls thymic NKT cell development by providing a signal that links Egr2 to induce PLZF, in part by regulating signaling lymphocyte activation molecule 6 expression. PMID:26519537

FATE OF PAH COMPOUNDS IN TWO SOIL TYPES: INFLUENCE OF VOLATILIZATION, ABIOTIC LOSS, AND BIOLOGICAL ACTIVITY

Science.gov (United States)

The fate of 14 polycyclic aromatic hydrocarbon (PAH) compounds was evaluated with regard to interphase transfer potential and mechanisms of treatment in soil under unsaturated conditions. Volatilization and abiotic and biotic fate of the PAHs were determined using two soils not p...

Using Neural Networks to Classify Digitized Images of Galaxies

Science.gov (United States)

Goderya, S. N.; McGuire, P. C.

2000-12-01

Automated classification of Galaxies into Hubble types is of paramount importance to study the large scale structure of the Universe, particularly as survey projects like the Sloan Digital Sky Survey complete their data acquisition of one million galaxies. At present it is not possible to find robust and efficient artificial intelligence based galaxy classifiers. In this study we will summarize progress made in the development of automated galaxy classifiers using neural networks as machine learning tools. We explore the Bayesian linear algorithm, the higher order probabilistic network, the multilayer perceptron neural network and Support Vector Machine Classifier. The performance of any machine classifier is dependant on the quality of the parameters that characterize the different groups of galaxies. Our effort is to develop geometric and invariant moment based parameters as input to the machine classifiers instead of the raw pixel data. Such an approach reduces the dimensionality of the classifier considerably, and removes the effects of scaling and rotation, and makes it easier to solve for the unknown parameters in the galaxy classifier. To judge the quality of training and classification we develop the concept of Mathews coefficients for the galaxy classification community. Mathews coefficients are single numbers that quantify classifier performance even with unequal prior probabilities of the classes.

FATES: a flexible analysis toolkit for the exploration of single-particle mass spectrometer data

Science.gov (United States)

Sultana, Camille M.; Cornwell, Gavin C.; Rodriguez, Paul; Prather, Kimberly A.

2017-04-01

Single-particle mass spectrometer (SPMS) analysis of aerosols has become increasingly popular since its invention in the 1990s. Today many iterations of commercial and lab-built SPMSs are in use worldwide. However, supporting analysis toolkits for these powerful instruments are outdated, have limited functionality, or are versions that are not available to the scientific community at large. In an effort to advance this field and allow better communication and collaboration between scientists, we have developed FATES (Flexible Analysis Toolkit for the Exploration of SPMS data), a MATLAB toolkit easily extensible to an array of SPMS designs and data formats. FATES was developed to minimize the computational demands of working with large data sets while still allowing easy maintenance, modification, and utilization by novice programmers. FATES permits scientists to explore, without constraint, complex SPMS data with simple scripts in a language popular for scientific numerical analysis. In addition FATES contains an array of data visualization graphic user interfaces (GUIs) which can aid both novice and expert users in calibration of raw data; exploration of the dependence of mass spectral characteristics on size, time, and peak intensity; and investigations of clustered data sets.

Technological Similarity, Post-acquisition R&D Reorganization, and Innovation Performance in Horizontal Acquisition

DEFF Research Database (Denmark)

Colombo, Massimo G.; Rabbiosi, Larissa

2014-01-01

This paper aims to disentangle the mechanisms through which technological similarity between acquiring and acquired firms influences innovation in horizontal acquisitions. We develop a theoretical model that links technological similarity to: (i) two key aspects of post-acquisition reorganization...... of acquired R&D operations – the rationalization of the R&D operations and the replacement of the R&D top manager, and (ii) two intermediate effects that are closely associated with the post-acquisition innovation performance of the combined firm – improvements in R&D productivity and disruptions in R......&D personnel. We rely on PLS techniques to test our theoretical model using detailed information on 31 horizontal acquisitions in high- and medium-tech industries. Our results indicate that in horizontal acquisitions, technological similarity negatively affects post-acquisition innovation performance...

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.

Lifelong learning of human actions with deep neural network self-organization.

Science.gov (United States)

Parisi, German I; Tani, Jun; Weber, Cornelius; Wermter, Stefan

2017-12-01

Lifelong learning is fundamental in autonomous robotics for the acquisition and fine-tuning of knowledge through experience. However, conventional deep neural models for action recognition from videos do not account for lifelong learning but rather learn a batch of training data with a predefined number of action classes and samples. Thus, there is the need to develop learning systems with the ability to incrementally process available perceptual cues and to adapt their responses over time. We propose a self-organizing neural architecture for incrementally learning to classify human actions from video sequences. The architecture comprises growing self-organizing networks equipped with recurrent neurons for processing time-varying patterns. We use a set of hierarchically arranged recurrent networks for the unsupervised learning of action representations with increasingly large spatiotemporal receptive fields. Lifelong learning is achieved in terms of prediction-driven neural dynamics in which the growth and the adaptation of the recurrent networks are driven by their capability to reconstruct temporally ordered input sequences. Experimental results on a classification task using two action benchmark datasets show that our model is competitive with state-of-the-art methods for batch learning also when a significant number of sample labels are missing or corrupted during training sessions. Additional experiments show the ability of our model to adapt to non-stationary input avoiding catastrophic interference. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Fast Inference of Deep Neural Networks in FPGAs for Particle Physics

Energy Technology Data Exchange (ETDEWEB)

Duarte, Javier [Fermilab; Han, Song [MIT; Harris, Philip [MIT; Jindariani, Sergo [Fermilab; Kreinar, Edward [EIS Intl., Herndon; Kreis, Benjamin [Fermilab; Ngadiuba, Jennifer [CERN; Pierini, Maurizio [CERN; Rivera, Ryan [Fermilab; Tran, Nhan [Fermilab; Wu, Zhenbin [Illinois U., Chicago

2018-04-16

Recent results at the Large Hadron Collider (LHC) have pointed to enhanced physics capabilities through the improvement of the real-time event processing techniques. Machine learning methods are ubiquitous and have proven to be very powerful in LHC physics, and particle physics as a whole. However, exploration of the use of such techniques in low-latency, low-power FPGA hardware has only just begun. FPGA-based trigger and data acquisition (DAQ) systems have extremely low, sub-microsecond latency requirements that are unique to particle physics. We present a case study for neural network inference in FPGAs focusing on a classifier for jet substructure which would enable, among many other physics scenarios, searches for new dark sector particles and novel measurements of the Higgs boson. While we focus on a specific example, the lessons are far-reaching. We develop a package based on High-Level Synthesis (HLS) called hls4ml to build machine learning models in FPGAs. The use of HLS increases accessibility across a broad user community and allows for a drastic decrease in firmware development time. We map out FPGA resource usage and latency versus neural network hyperparameters to identify the problems in particle physics that would benefit from performing neural network inference with FPGAs. For our example jet substructure model, we fit well within the available resources of modern FPGAs with a latency on the scale of 100 ns.

Occurrence, sources, and fate of pharmaceuticals in aquatic environment and soil

International Nuclear Information System (INIS)

Li, W.C.

2014-01-01

With the rapid economic development, a better living condition leads to longer life expectancy, which increased the total population, in particular the elderly group. It may result in increase in the demand of pharmaceuticals for people in domestic use or in hospital. Although most sewage treatment plants or waste water treatment plantsmet the regulatory requirement, there are still many pharmaceuticals removed incompletely and thus discharged to the environment. Therefore, the pharmaceuticals residue draws the public concern because they might cause adverse effects on the organism even human beings. Recently, many studies have published on the source and occurrence as well as the fate of pharmaceuticals all over the world. This paper summarized and reviewed the recent studies on the sources, occurrence, fate and the effects of the most common pharmaceuticals. Finally, it gave the suggestion and risk management for controlling the pharmaceuticals. - Highlights: • The sources of pharmaceutical residuals are studied. • Occurrence and fate of pharmaceutical in environment are studied. • Risk management and recommendation are provided on pharmaceutical pollution. - Concentration of pharmaceuticals in the natural environment is lower than in effluent of sewage treatment plants in which carbamazepine is found frequently in soil and water body

Biokinetics of zinc oxide nanoparticles: toxicokinetics, biological fates, and protein interaction

Directory of Open Access Journals (Sweden)

Choi SJ

2014-12-01

Full Text Available Soo-Jin Choi,1 Jin-Ho Choy2 1Department of Food Science and Technology, Seoul Women's University, 2Center for Intelligent Nano Bio Materials (CINBM, Department of Bioinspired Science and Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, South Korea Abstract: Biokinetic studies of zinc oxide (ZnO nanoparticles involve systematic and quantitative analyses of absorption, distribution, metabolism, and excretion in plasma and tissues of whole animals after exposure. A full understanding of the biokinetics provides basic information about nanoparticle entry into systemic circulation, target organs of accumulation and toxicity, and elimination time, which is important for predicting the long-term toxic potential of nanoparticles. Biokinetic behaviors can be dependent on physicochemical properties, dissolution property in biological fluids, and nanoparticle–protein interaction. Moreover, the determination of biological fates of ZnO nanoparticles in the systemic circulation and tissues is critical in interpreting biokinetic behaviors and predicting toxicity potential as well as mechanism. This review focuses on physicochemical factors affecting the biokinetics of ZnO nanoparticles, in concert with understanding bioavailable fates and their interaction with proteins. Keywords: ZnO nanoparticles, biokinetics, distribution, excretion, fate, interaction

Endothelial ERK signaling controls lymphatic fate specification

Science.gov (United States)

Deng, Yong; Atri, Deepak; Eichmann, Anne; Simons, Michael

2013-01-01

Lymphatic vessels are thought to arise from PROX1-positive endothelial cells (ECs) in the cardinal vein in response to induction of SOX18 expression; however, the molecular event responsible for increased SOX18 expression has not been established. We generated mice with endothelial-specific, inducible expression of an RAF1 gene with a gain-of-function mutation (RAF1S259A) that is associated with Noonan syndrome. Expression of mutant RAF1S259A in ECs activated ERK and induced SOX18 and PROX1 expression, leading to increased commitment of venous ECs to the lymphatic fate. Excessive production of lymphatic ECs resulted in lymphangiectasia that was highly reminiscent of abnormal lymphatics seen in Noonan syndrome and similar “RASopathies.” Inhibition of ERK signaling during development abrogated the lymphatic differentiation program and rescued the lymphatic phenotypes induced by expression of RAF1S259A. These data suggest that ERK activation plays a key role in lymphatic EC fate specification and that excessive ERK activation is the basis of lymphatic abnormalities seen in Noonan syndrome and related diseases. PMID:23391722

Developing and using expert systems and neural networks in medicine: a review on benefits and challenges.

Science.gov (United States)

Sheikhtaheri, Abbas; Sadoughi, Farahnaz; Hashemi Dehaghi, Zahra

2014-09-01

Complicacy of clinical decisions justifies utilization of information systems such as artificial intelligence (e.g. expert systems and neural networks) to achieve better decisions, however, application of these systems in the medical domain faces some challenges. We aimed at to review the applications of these systems in the medical domain and discuss about such challenges. Following a brief introduction of expert systems and neural networks by representing few examples, the challenges of these systems in the medical domain are discussed. We found that the applications of expert systems and artificial neural networks have been increased in the medical domain. These systems have shown many advantages such as utilization of experts' knowledge, gaining rare knowledge, more time for assessment of the decision, more consistent decisions, and shorter decision-making process. In spite of all these advantages, there are challenges ahead of developing and using such systems including maintenance, required experts, inputting patients' data into the system, problems for knowledge acquisition, problems in modeling medical knowledge, evaluation and validation of system performance, wrong recommendations and responsibility, limited domains of such systems and necessity of integrating such systems into the routine work flows. We concluded that expert systems and neural networks can be successfully used in medicine; however, there are many concerns and questions to be answered through future studies and discussions.

Fate factors and emission flux estimates for emerging contaminants in surface waters

Directory of Open Access Journals (Sweden)

Hoa T. Trinh

2016-01-01

Full Text Available Pharmaceuticals, personal care products, hormones, and wastewater products are emerging environmental concerns for manifold reasons, including the potential of some compounds found in these products for endocrine disruption at a very low chronic exposure level. The environmental occurrences and sources of these contaminants in the water, soil, sediment and biota in European nations and the United States are well documented. This work reports a screening-level emission and fate assessment of thirty compounds, listed in the National Reconnaissance of the United States Geological Survey (USGS, 1999–2000 as the most frequently detected organic wastewater contaminants in U.S. streams and rivers. Estimations of the surface water fate factors were based on Level II and Level III multimedia fugacity models for a 1000 km2 model environment, the size of a typical county in the eastern United States. The compounds are categorized into three groups based upon the sensitivity of their predicted surface water fate factors to uncertainties in their physicochemical property values and the landscape parameters. The environmental fate factors, mass distributions, and loss pathways of all of the compounds are strongly affected by their assumed modes of entry into the environment. It is observed that for thirteen of the thirty organic wastewater contaminants most commonly detected in surface waters, conventional treatment strategies may be ineffective for their removal from wastewater effluents. The surface water fate factors predicted by the fugacity models were used in conjunction with the surface water concentrations measured in the USGS reconnaissance to obtain emission flux estimates for the compounds into U.S. streams and rivers. These include estimated fluxes of 6.8 × 10−5 to 0.30 kg/h km2 for the biomarker coprostanol; 1.7 × 10−5 to 6.5 × 10−5 kg/h km2 for the insect repellent N,N-diethyltoluamide; and 4.3 × 10−6 to 3.1 × 10−5 kg/h km2 for

Msx2 alters the timing of retinal ganglion cells fate commitment and differentiation

Energy Technology Data Exchange (ETDEWEB)

Jiang, Shao-Yun, E-mail: jiangshaoyun@yahoo.com [School of Dentistry, Tianjin Medical University, 12 Qi Xiang Tai Street, Tianjin 300070 (China); Wang, Jian-Tao, E-mail: wangjiantao65@hotmail.com [Eye Center, Tianjin Medical University, 64 Tongan Road, Tianjin 300070 (China); Dohney Eye Institute, Keck School of Medicine, University of Southern California, 1355 San Pablo Street, DOH 314, Los Angeles, CA 90033 (United States)

2010-05-14

Timing of cell fate commitment determines distinct retinal cell types, which is believed to be controlled by a tightly coordinated regulatory program of proliferation, cell cycle exit and differentiation. Although homeobox protein Msx2 could induce apoptosis of optic vesicle, it is unclear whether Msx2 regulates differentiation and cell fate commitment of retinal progenitor cells (RPCs) to retinal ganglion cells (RGCs). In this study, we show that overexpression of Msx2 transiently suppressed the expression of Cyclin D1 and blocked cell proliferation. Meanwhile, overexpression of Msx2 delayed the expression of RGC-specific differentiation markers (Math5 and Brn3b), which showed that Msx2 could affect the timing of RGCs fate commitment and differentiation by delaying the timing of cell cycle exit of retinal progenitors. These results indicate Msx2 possesses dual regulatory functions in controlling cell cycle progression of retinal RPCs and timing of RGCs differentiation.

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)

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.

Psychological and neural mechanisms of experimental extinction: a selective review.

Science.gov (United States)

Delamater, Andrew R; Westbrook, R Frederick

2014-02-01

The present review examines key psychological concepts in the study of experimental extinction and implications these have for an understanding of the underlying neurobiology of extinction learning. We suggest that many of the signature characteristics of extinction learning (spontaneous recovery, renewal, reinstatement, rapid reacquisition) can be accommodated by the standard associative learning theory assumption that extinction results in partial erasure of the original learning together with new inhibitory learning. Moreover, we consider recent behavioral and neural evidence that supports the partial erasure view of extinction, but also note shortcomings in our understanding of extinction circuits as these relate to the negative prediction error concept. Recent work suggests that common prediction error and stimulus-specific prediction error terms both may be required to explain neural plasticity both in acquisition and extinction learning. In addition, we suggest that many issues in the content of extinction learning have not been fully addressed in current research, but that neurobiological approaches should be especially helpful in addressing such issues. These include questions about the nature of extinction learning (excitatory CS-No US, inhibitory CS-US learning, occasion setting processes), especially as this relates to studies of the micro-circuitry of extinction, as well as its representational content (sensory, motivational, response). An additional understudied problem in extinction research is the role played by attention processes and their underlying neural networks, although some research and theory converge on the idea that extinction is accompanied by attention decrements (i.e., habituation-like processes). Copyright © 2013 Elsevier Inc. All rights reserved.

Illustrating sensitivity in environmental fate models using partitioning maps - application to selected contaminants

Energy Technology Data Exchange (ETDEWEB)

Meyer, T.; Wania, F. [Univ. of Toronto at Scarborough - DPES, Toronto (Canada)

2004-09-15

Generic environmental multimedia fate models are important tools in the assessment of the impact of organic pollutants. Because of limited possibilities to evaluate generic models by comparison with measured data and the increasing regulatory use of such models, uncertainties of model input and output are of considerable concern. This led to a demand for sensitivity and uncertainty analyses for the outputs of environmental fate models. Usually, variations of model predictions of the environmental fate of organic contaminants are analyzed for only one or at most a few selected chemicals, even though parameter sensitivity and contribution to uncertainty are widely different for different chemicals. We recently presented a graphical method that allows for the comprehensive investigation of model sensitivity and uncertainty for all neutral organic chemicals simultaneously. This is achieved by defining a two-dimensional hypothetical ''chemical space'' as a function of the equilibrium partition coefficients between air, water, and octanol (K{sub OW}, K{sub AW}, K{sub OA}), and plotting sensitivity and/or uncertainty of a specific model result to each input parameter as function of this chemical space. Here we show how such sensitivity maps can be used to quickly identify the variables with the highest influence on the environmental fate of selected, chlorobenzenes, polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), hexachlorocyclohexanes (HCHs) and brominated flame retardents (BFRs).

Prenatal Nicotine Exposure Disrupts Infant Neural Markers of Orienting.

Science.gov (United States)

King, Erin; Campbell, Alana; Belger, Aysenil; Grewen, Karen

2017-08-17

Prenatal nicotine exposure (PNE) from maternal cigarette-smoking is linked to developmental deficits, including impaired auditory processing, language, generalized intelligence, attention and sleep. Fetal brain undergoes massive growth, organization and connectivity during gestation, making it particularly vulnerable to neurotoxic insult. Nicotine binds to nicotinic acetylcholine receptors, which are extensively involved in growth, connectivity and function of developing neural circuitry and neurotransmitter systems. Thus, PNE may have long-term impact on neurobehavioral development. The purpose of this study was to compare the auditory K-complex, an event-related potential reflective of auditory gating, sleep preservation and memory consolidation during sleep, in infants with and without PNE and to relate these neural correlates to neurobehavioral development. We compared brain responses to an auditory paired-click paradigm in 3 to 5-month-old infants during Stage 2 sleep, when the K-complex is best observed. We measured component amplitude and delta activity during the K-complex. PNE may impair auditory sensory gating, which may contribute to disrupted sleep and to reduced auditory discrimination and learning, attention re-orienting and/or arousal during wakefulness reported in other studies. Links between PNE and reduced K-complex amplitude and delta power may represent altered cholinergic and GABAergic synaptic programming, and possibly reflect early neural bases for PNE-linked disruptions in sleep quality and auditory processing. These may pose significant disadvantage for language acquisition, attention, and social interaction necessary for academic and social success. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A computational framework for ultrastructural mapping of neural circuitry.

Directory of Open Access Journals (Sweden)

James R Anderson

2009-03-01

Full Text Available Circuitry mapping of metazoan neural systems is difficult because canonical neural regions (regions containing one or more copies of all components are large, regional borders are uncertain, neuronal diversity is high, and potential network topologies so numerous that only anatomical ground truth can resolve them. Complete mapping of a specific network requires synaptic resolution, canonical region coverage, and robust neuronal classification. Though transmission electron microscopy (TEM remains the optimal tool for network mapping, the process of building large serial section TEM (ssTEM image volumes is rendered difficult by the need to precisely mosaic distorted image tiles and register distorted mosaics. Moreover, most molecular neuronal class markers are poorly compatible with optimal TEM imaging. Our objective was to build a complete framework for ultrastructural circuitry mapping. This framework combines strong TEM-compliant small molecule profiling with automated image tile mosaicking, automated slice-to-slice image registration, and gigabyte-scale image browsing for volume annotation. Specifically we show how ultrathin molecular profiling datasets and their resultant classification maps can be embedded into ssTEM datasets and how scripted acquisition tools (SerialEM, mosaicking and registration (ir-tools, and large slice viewers (MosaicBuilder, Viking can be used to manage terabyte-scale volumes. These methods enable large-scale connectivity analyses of new and legacy data. In well-posed tasks (e.g., complete network mapping in retina, terabyte-scale image volumes that previously would require decades of assembly can now be completed in months. Perhaps more importantly, the fusion of molecular profiling, image acquisition by SerialEM, ir-tools volume assembly, and data viewers/annotators also allow ssTEM to be used as a prospective tool for discovery in nonneural systems and a practical screening methodology for neurogenetics. Finally

Sources and fate of environmental radioactivity at the earth's surface

International Nuclear Information System (INIS)

El-Daoushy, F.

2010-01-01

Sources and fate of environmental radioactivity at the earth surface This is to link environmental radioactivity to RP in Africa? To describe the benefits of Africa from this field in terms of RP, safety and security policies. To create a mission and a vision to fulfil the needs of ONE PEOPLE, ONE GOAL, ONE FAITH. Sources, processes and fate of environmental radioactivity Previous experience helps setting up an African agenda.(1) Factors influencing cosmogenic radionuclides(2) Factors influencing artificial radionuclides: (a) nuclear weapon-tests (b) nuclear accidents (c) Energy, mining and industrial waste (3) Factors influencing the global Rn-222 and its daughters. (4) Dynamics of cycles of natural radioactivity, e.g. Pb-210. (5) Environmental radiotracers act as DIAGNOSTIC TOOLS to assess air and water quality and impacts of the atmospheric and hydrospheric compartments on ecosystems.6) Definition of base-lines for rehabilitation and protection. Climate influences sources/behaviour/fate of environmental radioactivity. Impacts on life forms in Africa would be severe. Assessing environmental radioactivity resolves these issue

Applications of neural networks to real-time data processing at the Environmental and Molecular Sciences Laboratory (EMSL)

International Nuclear Information System (INIS)

Keller, P.E.; Kouzes, R.T.; Kangas, L.J.

1993-06-01

Detailed design of the Environmental and Molecular Sciences Laboratory (EMSL) at the Pacific Northwest Laboratory (PNL) is nearing completion and construction is scheduled to begin later this year. This facility will assist in the environmental restoration and waste management mission at the Hanford Site. This paper identifies several real-time data processing applications within the EMSL where neural networks can potentially be beneficial. These applications include real-time sensor data acquisition and analysis, spectral analysis, process control, theoretical modeling, and data compression

Fates of trees damaged by logging in Amazonian Bolivia

NARCIS (Netherlands)

Shenkin, A.; Bolker, B.; Peña Claros, M.; Licona, J.C.; Putz, F.E.

2015-01-01

Estimation of carbon losses from trees felled and incidentally-killed during selective logging of tropical forests is relatively straightforward and well-documented, but less is known about the fates of collaterally-damaged trees that initially survive. Tree response to logging damage is an

75 FR 54524 - Defense Federal Acquisition Regulation Supplement; Acquisition Strategies To Ensure Competition...

Science.gov (United States)

2010-09-08

...., because the changes are to internal Government organization and operating procedures only. The rule... 48 CFR Part 207 Government procurement. Ynette R. Shelkin, Editor, Defense Acquisition Regulations... Life Cycle of Major Defense Acquisition Programs (DFARS Case 2009-D014) AGENCY: Defense Acquisition...

CD133-enriched Xeno-Free human embryonic-derived neural stem cells expand rapidly in culture and do not form teratomas in immunodeficient mice

Directory of Open Access Journals (Sweden)

Daniel L. Haus

2014-09-01

Full Text Available Common methods for the generation of human embryonic-derived neural stem cells (hNSCs result in cells with potentially compromised safety profiles due to maintenance of cells in conditions containing non-human proteins (e.g. in bovine serum or on mouse fibroblast feeders. Additionally, sufficient expansion of resulting hNSCs for scaling out or up in a clinically relevant time frame has proven to be difficult. Here, we report a strategy that produces hNSCs in completely “Xeno-Free” culture conditions. Furthermore, we have enriched the hNSCs for the cell surface marker CD133 via magnetic sorting, which has led to an increase in the expansion rate and neuronal fate specification of the hNSCs in vitro. Critically, we have also confirmed neural lineage specificity upon sorted hNSC transplantation into the immunodeficient NOD-scid mouse brain. The future use or adaptation of these protocols has the potential to better facilitate the advancement of pre-clinical strategies from the bench to the bedside.

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.

Building 235-F Goldsim Fate And Transport Model

Energy Technology Data Exchange (ETDEWEB)

Taylor, G. A.; Phifer, M. A.

2012-09-14

Savannah River National Laboratory (SRNL) personnel, at the request of Area Completion Projects (ACP), evaluated In-Situ Disposal (ISD) alternatives that are under consideration for deactivation and decommissioning (D&D) of Building 235-F and the Building 294-2F Sand Filter. SRNL personnel developed and used a GoldSim fate and transport model, which is consistent with Musall 2012, to evaluate relative to groundwater protection, ISD alternatives that involve either source removal and/or the grouting of portions or all of 235-F. This evaluation was conducted through the development and use of a Building 235-F GoldSim fate and transport model. The model simulates contaminant release from four 235-F process areas and the 294-2F Sand Filter. In addition, it simulates the fate and transport through the vadose zone, the Upper Three Runs (UTR) aquifer, and the Upper Three Runs (UTR) creek. The model is designed as a stochastic model, and as such it can provide both deterministic and stochastic (probabilistic) results. The results show that the median radium activity concentrations exceed the 5 ?Ci/L radium MCL at the edge of the building for all ISD alternatives after 10,000 years, except those with a sufficient amount of inventory removed. A very interesting result was that grouting was shown to basically have minimal effect on the radium activity concentration. During the first 1,000 years grouting may have some small positive benefit relative to radium, however after that it may have a slightly deleterious effect. The Pb-210 results, relative to its 0.06 ?Ci/L PRG, are essentially identical to the radium results, but the Pb-210 results exhibit a lesser degree of exceedance. In summary, some level of inventory removal will be required to ensure that groundwater standards are met.

Building 235-F Goldsim Fate And Transport Model

International Nuclear Information System (INIS)

Taylor, G. A.; Phifer, M. A.

2012-01-01

Savannah River National Laboratory (SRNL) personnel, at the request of Area Completion Projects (ACP), evaluated In-Situ Disposal (ISD) alternatives that are under consideration for deactivation and decommissioning (D and D) of Building 235-F and the Building 294-2F Sand Filter. SRNL personnel developed and used a GoldSim fate and transport model, which is consistent with Musall 2012, to evaluate relative to groundwater protection, ISD alternatives that involve either source removal and/or the grouting of portions or all of 235-F. This evaluation was conducted through the development and use of a Building 235-F GoldSim fate and transport model. The model simulates contaminant release from four 235-F process areas and the 294-2F Sand Filter. In addition, it simulates the fate and transport through the vadose zone, the Upper Three Runs (UTR) aquifer, and the Upper Three Runs (UTR) creek. The model is designed as a stochastic model, and as such it can provide both deterministic and stochastic (probabilistic) results. The results show that the median radium activity concentrations exceed the 5 ρCi/L radium MCL at the edge of the building for all ISD alternatives after 10,000 years, except those with a sufficient amount of inventory removed. A very interesting result was that grouting was shown to basically have minimal effect on the radium activity concentration. During the first 1,000 years grouting may have some small positive benefit relative to radium, however after that it may have a slightly deleterious effect. The Pb-210 results, relative to its 0.06 ρCi/L PRG, are essentially identical to the radium results, but the Pb-210 results exhibit a lesser degree of exceedance. In summary, some level of inventory removal will be required to ensure that groundwater standards are met

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

Regulation of adult neural progenitor cell functions by purinergic signaling.

Science.gov (United States)

Tang, Yong; Illes, Peter

2017-02-01

Extracellular purines are signaling molecules in the neurogenic niches of the brain and spinal cord, where they activate cell surface purinoceptors at embryonic neural stem cells (NSCs) and adult neural progenitor cells (NPCs). Although mRNA and protein are expressed at NSCs/NPCs for almost all subtypes of the nucleotide-sensitive P2X/P2Y, and the nucleoside-sensitive adenosine receptors, only a few of those have acquired functional significance. ATP is sequentially degraded by ecto-nucleotidases to ADP, AMP, and adenosine with agonistic properties for distinct receptor-classes. Nucleotides/nucleosides facilitate or inhibit NSC/NPC proliferation, migration and differentiation. The most ubiquitous effect of all agonists (especially of ATP and ADP) appears to be the facilitation of cell proliferation, usually through P2Y1Rs and sometimes through P2X7Rs. However, usually P2X7R activation causes necrosis/apoptosis of NPCs. Differentiation can be initiated by P2Y2R-activation or P2X7R-blockade. A key element in the transduction mechanism of either receptor is the increase of the intracellular free Ca 2+ concentration, which may arise due to its release from intracellular storage sites (G protein-coupling; P2Y) or due to its passage through the receptor-channel itself from the extracellular space (ATP-gated ion channel; P2X). Further research is needed to clarify how purinergic signaling controls NSC/NPC fate and how the balance between the quiescent and activated states is established with fine and dynamic regulation. GLIA 2017;65:213-230. © 2016 Wiley Periodicals, Inc.

Neural chips, neural computers and application in high and superhigh energy physics experiments

International Nuclear Information System (INIS)

Nikityuk, N.M.; )

2001-01-01

Architecture peculiarity and characteristics of series of neural chips and neural computes used in scientific instruments are considered. Tendency of development and use of them in high energy and superhigh energy physics experiments are described. Comparative data which characterize the efficient use of neural chips for useful event selection, classification elementary particles, reconstruction of tracks of charged particles and for search of hypothesis Higgs particles are given. The characteristics of native neural chips and accelerated neural boards are considered [ru

The C. elegans TPR Containing Protein, TRD-1, Regulates Cell Fate Choice in the Developing Germ Line and Epidermis.

Directory of Open Access Journals (Sweden)

Samantha Hughes

Full Text Available Correct cell fate choice is crucial in development. In post-embryonic development of the hermaphroditic Caenorhabitis elegans, distinct cell fates must be adopted in two diverse tissues. In the germline, stem cells adopt one of three possible fates: mitotic cell cycle, or gamete formation via meiosis, producing either sperm or oocytes. In the epidermis, the stem cell-like seam cells divide asymmetrically, with the daughters taking on either a proliferative (seam or differentiated (hypodermal or neuronal fate. We have isolated a novel conserved C. elegans tetratricopeptide repeat containing protein, TRD-1, which is essential for cell fate determination in both the germline and the developing epidermis and has homologs in other species, including humans (TTC27. We show that trd-1(RNAi and mutant animals have fewer seam cells as a result of inappropriate differentiation towards the hypodermal fate. In the germline, trd-1 RNAi results in a strong masculinization phenotype, as well as defects in the mitosis to meiosis switch. Our data suggests that trd-1 acts downstream of tra-2 but upstream of fem-3 in the germline sex determination pathway, and exhibits a constellation of phenotypes in common with other Mog (masculinization of germline mutants. Thus, trd-1 is a new player in both the somatic and germline cell fate determination machinery, suggestive of a novel molecular connection between the development of these two diverse tissues.

Neural correlates of foreign-language learning in childhood: a 3-year longitudinal ERP study.

Science.gov (United States)

Ojima, Shiro; Nakamura, Naoko; Matsuba-Kurita, Hiroko; Hoshino, Takahiro; Hagiwara, Hiroko

2011-01-01

A foreign language (a language not spoken in one's community) is difficult to master completely. Early introduction of foreign-language (FL) education during childhood is becoming a standard in many countries. However, the neural process of child FL learning still remains largely unknown. We longitudinally followed 322 school-age children with diverse FL proficiency for three consecutive years, and acquired children's ERP responses to FL words that were semantically congruous or incongruous with the preceding picture context. As FL proficiency increased, various ERP components previously reported in mother-tongue (L1) acquisition (such as a broad negativity, an N400, and a late positive component) appeared sequentially, critically in an identical order to L1 acquisition. This finding was supported not only by cross-sectional analyses of children at different proficiency levels but also by longitudinal analyses of the same children over time. Our data are consistent with the hypothesis that FL learning in childhood reproduces identical developmental stages in an identical order to L1 acquisition, suggesting that the nature of the child's brain itself may determine the normal course of FL learning. Future research should test the generalizability of the results in other aspects of language such as syntax.

Neural tissue-spheres

DEFF Research Database (Denmark)

Andersen, Rikke K; Johansen, Mathias; Blaabjerg, Morten

2007-01-01

By combining new and established protocols we have developed a procedure for isolation and propagation of neural precursor cells from the forebrain subventricular zone (SVZ) of newborn rats. Small tissue blocks of the SVZ were dissected and propagated en bloc as free-floating neural tissue...... content, thus allowing experimental studies of neural precursor cells and their niche...

Fate and transformation of graphene oxide in marine waters

Science.gov (United States)

One common use of graphene family nanomaterials (GFNs) is as functional and/or antifouling coatings, which may ultimately lead to their release into the natural environment. The fate of graphene oxide (GO), a common type of GFN, in natural waters is currently not well understood....

40 CFR 158.1300 - Environmental fate data requirements table.

Science.gov (United States)

2010-07-01

... transformation products. 7. Environmental chemistry methods used to generate data associated with this study must... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Environmental fate data requirements table. 158.1300 Section 158.1300 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas

DEFF Research Database (Denmark)

Herrtwich, Laura; Nanda, Indrajit; Evangelou, Konstantinos

2016-01-01

to a chronic stimulus, though critical for disease outcome, have not been defined. Here, we delineate a macrophage differentiation pathway by which a persistent Toll-like receptor (TLR) 2 signal instructs polyploid macrophage fate by inducing replication stress and activating the DNA damage response. Polyploid...

Pak2 Controls Acquisition of NKT Cell Fate by Regulating Expression of the Transcription Factors PLZF and Egr2.

Science.gov (United States)

O'Hagan, Kyle L; Zhao, Jie; Pryshchep, Olga; Wang, Chyung-Ru; Phee, Hyewon

2015-12-01

NKT cells constitute a small population of T cells developed in the thymus that produce large amounts of cytokines and chemokines in response to lipid Ags. Signaling through the Vα14-Jα18 TCR instructs commitment to the NKT cell lineage, but the precise signaling mechanisms that instruct their lineage choice are unclear. In this article, we report that the cytoskeletal remodeling protein, p21-activated kinase 2 (Pak2), was essential for NKT cell development. Loss of Pak2 in T cells reduced stage III NKT cells in the thymus and periphery. Among different NKT cell subsets, Pak2 was necessary for the generation and function of NKT1 and NKT2 cells, but not NKT17 cells. Mechanistically, expression of Egr2 and promyelocytic leukemia zinc finger (PLZF), two key transcription factors for acquiring the NKT cell fate, were markedly diminished in the absence of Pak2. Diminished expression of Egr2 and PLZF were not caused by aberrant TCR signaling, as determined using a Nur77-GFP reporter, but were likely due to impaired induction and maintenance of signaling lymphocyte activation molecule 6 expression, a TCR costimulatory receptor required for NKT cell development. These data suggest that Pak2 controls thymic NKT cell development by providing a signal that links Egr2 to induce PLZF, in part by regulating signaling lymphocyte activation molecule 6 expression. Copyright © 2015 by The American Association of Immunologists, Inc.

Acquisitions Everywhere: Modeling an Acquisitions Data Standard to Connect a Distributed Environment

OpenAIRE

Hanson, Eric M.; Lightcap, Paul W.; Miguez, Matthew R.

2016-01-01

Acquisitions functions remain operationally crucial in providing access to paid information resources, but data formats and workflows utilized within library acquisitions remain primarily within the traditional integrated library system (ILS). As libraries have evolved to use distributed systems to manage information resources, so too must acquisitions functions adapt to an environment that may include the ILS, e‐resource management systems (ERMS), institutional repositories (IR), and other d...

48 CFR 434.004 - Acquisition strategy.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Acquisition strategy. 434.004 Section 434.004 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE SPECIAL CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION General 434.004 Acquisition strategy. (a) The program...

Explanation of the degree of Divine Knowledge in the degree of Decrees of fate in Molla Sadra and Allama Tabatabai's views

Directory of Open Access Journals (Sweden)

Ali Reza Khwajegir

Full Text Available The Sadraee's transcendental philosophy in theology affected by the authentic Divinity texts and discussions and has inspired in resolving many of the theological and philosophical problems of this school. Therefore, this school can be considered as the most prominent school. Although, Molla sadra does not know enough the argument and arguing without conscience and purification of self, but, the most based on imported sources of revelation and interpretations of Imams (AS and believes that truths of faith are not possible except by purifying heart from the whims, thinking of the Divine verses, hadith of the Prophet (The Prophet's massage and his tribe, and following the way of the pious men. Proposing the problem of Divine Decrees of fate in transcendental philosophy and explaining its principles that brought up in both the philosophical texts and exegesis of the followers of transcendental philosophy are of the most important Instances that this school takes impression from religious texts. Decrees of fate has various levels, such as essential and actual, scientific and objective, divine creation and divine legislation, fixed and variable, that is every level take into consideration the discussion of Divine Decrees of fate from a particular direction. Divine Decrees of fate in one dimension is related to the degrees of Divine knowledge and the quality of Divine knowledge on what is apart from God, on the other dimension, is related to the question of the necessity of The existence system and the quality of causal connection between the elements of the universe and the origin of necessity of The existence system that has been expressed in these schools with a certain thoughtfulness in both theology and cosmology. Divine Decrees of fate in comparing with universal realms of existence is considered the same as degree of intellectual forms beyond the spiritual and natural forms that emanated from the god, suddenly and timelessly and called one of

Explanation of the degree of Divine Knowledge in the degree of Decrees of fate in Molla Sadra and Allama Tabatabai's views

Directory of Open Access Journals (Sweden)

Alireza Khajegir

2013-08-01

Full Text Available The Sadraee's transcendental philosophy in theology affected by the authentic Divinity texts and discussions and has inspired in resolving many of the theological and philosophical problems of this school. Therefore, this school can be considered as the most prominent school. Although, Molla sadra does not know enough the argument and arguing without conscience and purification of self, but, the most based on imported sources of revelation and interpretations of Imams (AS and believes that truths of faith are not possible except by purifying heart from the whims, thinking of the Divine verses, hadith of the Prophet (The Prophet's massage and his tribe, and following the way of the pious men. Proposing the problem of Divine Decrees of fate in transcendental philosophy and explaining its principles that brought up in both the philosophical texts and exegesis of the followers of transcendental philosophy are of the most important Instances that this school takes impression from religious texts.    Decrees of fate has various levels,  such as essential and actual, scientific and objective, divine creation and divine legislation, fixed and variable, that is every level take into consideration the discussion of Divine Decrees of fate from a particular direction. Divine Decrees of fate in one dimension is related to the degrees of Divine knowledge and the quality of Divine knowledge on what is apart from God, on the other dimension, is related to the question of the necessity of The existence system and the quality of causal connection between the elements of the universe and the origin of necessity of The existence system that has been expressed in these schools with a certain thoughtfulness in both theology and cosmology. Divine Decrees of fate in comparing with universal realms of existence is considered the same as degree of intellectual forms beyond the spiritual and natural forms that emanated from the god, suddenly and timelessly and called

Real-time classification of signals from three-component seismic sensors using neural nets

Science.gov (United States)

Bowman, B. C.; Dowla, F.

1992-05-01

Adaptive seismic data acquisition systems with capabilities of signal discrimination and event classification are important in treaty monitoring, proliferation, and earthquake early detection systems. Potential applications include monitoring underground chemical explosions, as well as other military, cultural, and natural activities where characteristics of signals change rapidly and without warning. In these applications, the ability to detect and interpret events rapidly without falling behind the influx of the data is critical. We developed a system for real-time data acquisition, analysis, learning, and classification of recorded events employing some of the latest technology in computer hardware, software, and artificial neural networks methods. The system is able to train dynamically, and updates its knowledge based on new data. The software is modular and hardware-independent; i.e., the front-end instrumentation is transparent to the analysis system. The software is designed to take advantage of the multiprocessing environment of the Unix operating system. The Unix System V shared memory and static RAM protocols for data access and the semaphore mechanism for interprocess communications were used. As the three-component sensor detects a seismic signal, it is displayed graphically on a color monitor using X11/Xlib graphics with interactive screening capabilities. For interesting events, the triaxial signal polarization is computed, a fast Fourier Transform (FFT) algorithm is applied, and the normalized power spectrum is transmitted to a backpropagation neural network for event classification. The system is currently capable of handling three data channels with a sampling rate of 500 Hz, which covers the bandwidth of most seismic events. The system has been tested in laboratory setting with artificial events generated in the vicinity of a three-component sensor.

Acquisition, extinction, and recall of opiate reward memory are signaled by dynamic neuronal activity patterns in the prefrontal cortex.

Science.gov (United States)

Sun, Ninglei; Chi, Ning; Lauzon, Nicole; Bishop, Stephanie; Tan, Huibing; Laviolette, Steven R

2011-12-01

The medial prefrontal cortex (mPFC) comprises an important component in the neural circuitry underlying drug-related associative learning and memory processing. Neuronal activation within mPFC circuits is correlated with the recall of opiate-related drug-taking experiences in both humans and other animals. Using an unbiased associative place conditioning procedure, we recorded mPFC neuronal populations during the acquisition, recall, and extinction phases of morphine-related associative learning and memory. Our analyses revealed that mPFC neurons show increased activity both in terms of tonic and phasic activity patterns during the acquisition phase of opiate reward-related memory and demonstrate stimulus-locked associative activity changes in real time, during the recall of opiate reward memories. Interestingly, mPFC neuronal populations demonstrated divergent patterns of bursting activity during the acquisition versus recall phases of newly acquired opiate reward memory, versus the extinction of these memories, with strongly increased bursting during the recall of an extinction memory and no associative bursting during the recall of a newly acquired opiate reward memory. Our results demonstrate that neurons within the mPFC are involved in both the acquisition, recall, and extinction of opiate-related reward memories, showing unique patterns of tonic and phasic activity patterns during these separate components of the opiate-related reward learning and memory recall.

Modeling Engineered Nanomaterials (ENMs) Fate and Transport in Aquatic Ecosystems

Science.gov (United States)

Under the Toxic Substances Control Act (TSCA), the Environmental Protection Agency (EPA) is required to perform new chemical reviews of engineered nanomaterials (ENMs) identified in pre-manufacture notices. However, environmental fate models developed for traditional contaminants...

48 CFR 873.105 - Acquisition planning.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Acquisition planning. 873.105 Section 873.105 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS DEPARTMENT... planning. (a) Acquisition planning is an indispensable component of the total acquisition process. (b) For...

48 CFR 34.004 - Acquisition strategy.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Acquisition strategy. 34... CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION General 34.004 Acquisition strategy. The program manager, as specified in agency procedures, shall develop an acquisition strategy tailored to the particular...

48 CFR 3034.004 - Acquisition strategy.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Acquisition strategy. 3034.004 Section 3034.004 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND... Acquisition strategy. See (HSAR) 48 CFR 3009.570 for policy applicable to acquisition strategies that consider...

Multiphase CFD modeling of nearfield fate of sediment plumes

DEFF Research Database (Denmark)

Saremi, Sina; Hjelmager Jensen, Jacob

2014-01-01

Disposal of dredged material and the overflow discharge during the dredging activities is a matter of concern due to the potential risks imposed by the plumes on surrounding marine environment. This gives rise to accurately prediction of the fate of the sediment plumes released in ambient waters...

Environmental fate of pesticides applied on coffee crops in ...

African Journals Online (AJOL)

The aim of this paper was evaluate the environmental fate of pesticides applied in coffee crops in southeast of Brazil, using the level I fugacity model. Chemical and physical characteristics of the pesticides were considered in different environmental compartments and applied fugacity equations. The preliminary evaluation ...

γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation

Science.gov (United States)

D’Avanzo, Carla; Sliwinski, Christopher; Wagner, Steven L.; Tanzi, Rudolph E.; Kim, Doo Yeon; Kovacs, Dora M.

2015-01-01

Soluble γ-secretase modulators (SGSMs) selectively decrease toxic amyloid β (Aβ) peptides (Aβ42). However, their effect on the physiologic functions of γ-secretase has not been tested in human model systems. γ-Secretase regulates fate determination of neural progenitor cells. Thus, we studied the impact of SGSMs on the neuronal differentiation of ReNcell VM (ReN) human neural progenitor cells (hNPCs). Quantitative PCR analysis showed that treatment of neurosphere-like ReN cell aggregate cultures with γ-secretase inhibitors (GSIs), but not SGSMs, induced a 2- to 4-fold increase in the expression of the neuronal markers Tuj1 and doublecortin. GSI treatment also induced neuronal marker protein expression, as shown by Western blot analysis. In the same conditions, SGSM treatment selectively reduced endogenous Aβ42 levels by ∼80%. Mechanistically, we found that Notch target gene expressions were selectively inhibited by a GSI, not by SGSM treatment. We can assert, for the first time, that SGSMs do not affect the neuronal differentiation of hNPCs while selectively decreasing endogenous Aβ42 levels in the same conditions. Our results suggest that our hNPC differentiation system can serve as a useful model to test the impact of GSIs and SGSMs on both endogenous Aβ levels and γ-secretase physiologic functions including endogenous Notch signaling.—D’Avanzo, C., Sliwinski, C., Wagner, S. L., Tanzi, R. E., Kim, D. Y., Kovacs, D. M. γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation. PMID:25903103

Connecting Mitochondria, Metabolism, and Stem Cell Fate

Science.gov (United States)

Wanet, Anaïs; Arnould, Thierry; Najimi, Mustapha

2015-01-01

As sites of cellular respiration and energy production, mitochondria play a central role in cell metabolism. Cell differentiation is associated with an increase in mitochondrial content and activity and with a metabolic shift toward increased oxidative phosphorylation activity. The opposite occurs during reprogramming of somatic cells into induced pluripotent stem cells. Studies have provided evidence of mitochondrial and metabolic changes during the differentiation of both embryonic and somatic (or adult) stem cells (SSCs), such as hematopoietic stem cells, mesenchymal stem cells, and tissue-specific progenitor cells. We thus propose to consider those mitochondrial and metabolic changes as hallmarks of differentiation processes. We review how mitochondrial biogenesis, dynamics, and function are directly involved in embryonic and SSC differentiation and how metabolic and sensing pathways connect mitochondria and metabolism with cell fate and pluripotency. Understanding the basis of the crosstalk between mitochondria and cell fate is of critical importance, given the promising application of stem cells in regenerative medicine. In addition to the development of novel strategies to improve the in vitro lineage-directed differentiation of stem cells, understanding the molecular basis of this interplay could lead to the identification of novel targets to improve the treatment of degenerative diseases. PMID:26134242

Age of Acquisition Effects in Chinese EFL learners’ Delexicalized Verb and Collocation Acquisition

Directory of Open Access Journals (Sweden)

Miao Haiyan

2015-05-01

Full Text Available This paper investigates age of acquisition (AoA effects and the acquisition of delexicalized verbs and collocations in Chinese EFL learners, and explores the underlying reasons from the connectionist model for these learners’ acquisition characteristics. The data were collected through a translation test consisted of delexialized verb information section and English-Chinese and Chinese-English collocation parts, aiming to focus on Chinese EFL learners’ receptive and productive abilities respectively. As Chinese EFL is a nationally classroom-based practice beginning from early primary school, the pedagogical value and different phases of acquisition are thus taken into consideration in designing the translation test. Research results show that the effects of AoA are significant not only in the learners’ acquisition of individual delexicalized verbs but also in delexicalized collocations. Although learners have long begun to learn delexicalized verbs, their production indicates that early learning does not guarantee total acquisition, because their grasp of delexicalized verbs still stay at the senior middle school level. AoA effects significantly affect the recognition but not the production of collocations. Furthermore, a plateau effect occurs in learners’ acquisition of college-level delexicalized collocations, as their recognition and production have no processing advantages over earlier learned collocations.

Sustaining an Acquisition-based Growth Strategy

DEFF Research Database (Denmark)

Henningsson, Stefan; Toppenberg, Gustav; Shanks, Graeme

Value creating acquisitions are a major challenge for many firms. Our case study of Cisco Systems shows that an advanced Enterprise Architecture (EA) capability can contribute to the acquisition process through a) preparing the acquirer to become ‘acquisition ready’, b) identifying resource...... complementarity, c) directing and governing the integration process, and d) post-acquisition evaluation of the achieved integration and proposing ways forward. Using the EA capability in the acquisition process improves Cisco’s ability to rapidly capture value from its acquisitions and to sustain its acquisition...

48 CFR 234.004 - Acquisition strategy.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Acquisition strategy. 234..., DEPARTMENT OF DEFENSE SPECIAL CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION 234.004 Acquisition strategy. (1) See 209.570 for policy applicable to acquisition strategies that consider the use of lead system...

Hypoxia Epigenetically Confers Astrocytic Differentiation Potential on Human Pluripotent Cell-Derived Neural Precursor Cells

Directory of Open Access Journals (Sweden)

Tetsuro Yasui

2017-06-01

Full Text Available Human neural precursor cells (hNPCs derived from pluripotent stem cells display a high propensity for neuronal differentiation, but they require long-term culturing to differentiate efficiently into astrocytes. The mechanisms underlying this biased fate specification of hNPCs remain elusive. Here, we show that hypoxia confers astrocytic differentiation potential on hNPCs through epigenetic gene regulation, and that this was achieved by cooperation between hypoxia-inducible factor 1α and Notch signaling, accompanied by a reduction of DNA methylation level in the promoter region of a typical astrocyte-specific gene, Glial fibrillary acidic protein. Furthermore, we found that this hypoxic culture condition could be applied to rapid generation of astrocytes from Rett syndrome patient-derived hNPCs, and that these astrocytes impaired neuronal development. Thus, our findings shed further light on the molecular mechanisms regulating hNPC differentiation and provide attractive tools for the development of therapeutic strategies for treating astrocyte-mediated neurological disorders.

Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis.

Science.gov (United States)

Kawaguchi, Daichi; Furutachi, Shohei; Kawai, Hiroki; Hozumi, Katsuto; Gotoh, Yukiko

2013-01-01

Stem cells often divide asymmetrically to produce one stem cell and one differentiating cell, thus maintaining the stem cell pool. Although neural stem cells (NSCs) in the adult mouse subventricular zone have been suggested to divide asymmetrically, intrinsic cell fate determinants for asymmetric NSC division are largely unknown. Stem cell niches are important for stem cell maintenance, but the niche for the maintenance of adult quiescent NSCs has remained obscure. Here we show that the Notch ligand Delta-like 1 (Dll1) is required to maintain quiescent NSCs in the adult mouse subventricular zone. Dll1 protein is induced in activated NSCs and segregates to one daughter cell during mitosis. Dll1-expressing cells reside in close proximity to quiescent NSCs, suggesting a feedback signal for NSC maintenance by their sister cells and progeny. Our data suggest a model in which NSCs produce their own niche cells for their maintenance through asymmetric Dll1 inheritance at mitosis.

Selected microRNAs define cell fate determination of murine central memory CD8 T cells.

Directory of Open Access Journals (Sweden)

Gonzalo Almanza

2010-06-01

Full Text Available During an immune response T cells enter memory fate determination, a program that divides them into two main populations: effector memory and central memory T cells. Since in many systems protection appears to be preferentially mediated by T cells of the central memory it is important to understand when and how fate determination takes place. To date, cell intrinsic molecular events that determine their differentiation remains unclear. MicroRNAs are a class of small, evolutionarily conserved RNA molecules that negatively regulate gene expression, causing translational repression and/or messenger RNA degradation. Here, using an in vitro system where activated CD8 T cells driven by IL-2 or IL-15 become either effector memory or central memory cells, we assessed the role of microRNAs in memory T cell fate determination. We found that fate determination to central memory T cells is under the balancing effects of a discrete number of microRNAs including miR-150, miR-155 and the let-7 family. Based on miR-150 a new target, KChIP.1 (K (+ channel interacting protein 1, was uncovered, which is specifically upregulated in developing central memory CD8 T cells. Our studies indicate that cell fate determination such as surface phenotype and self-renewal may be decided at the pre-effector stage on the basis of the balancing effects of a discrete number of microRNAs. These results may have implications for the development of T cell vaccines and T cell-based adoptive therapies.

Is Neural Processing of Negative Stimuli Altered in Addiction Independent of Drug Effects? Findings From Drug-Naïve Youth with Internet Gaming Disorder.

Science.gov (United States)

Yip, Sarah W; Gross, James J; Chawla, Megha; Ma, Shan-Shan; Shi, Xing-Hui; Liu, Lu; Yao, Yuan-Wei; Zhu, Lei; Worhunsky, Patrick D; Zhang, Jintao

2018-05-01

Difficulties in emotion regulation are commonly reported among individuals with alcohol and drug addictions and contribute to the acquisition and maintenance of addictive behaviors. Alterations in neural processing of negative affective stimuli have further been demonstrated among individuals with addictions. However, it is unclear whether these alterations are a general feature of addictions or are a result of prolonged exposure to drugs of abuse. To test the hypothesis of altered negative affect processing independent of drug effects, this study assessed neural function among drug-naïve youth with a behavioral addiction-Internet gaming disorder (IGD). Fifty-six young adults (28 with IGD, 28 matched controls) participated in fMRI scanning during performance of a well-validated emotion regulation task. Between-group differences in neural activity during task performance were assessed using a whole-brain, mixed-effects ANOVA with correction for multiple comparisons at currently recommended thresholds (voxel-level peffects.

Tbx1 and Jag1 act in concert to modulate the fate of neurosensory cells of the mouse otic vesicle

Directory of Open Access Journals (Sweden)

Stephania Macchiarulo

2017-10-01

Full Text Available The domain within the otic vesicle (OV known as the neurosensory domain (NSD, contains cells that will give rise to the hair and support cells of the otic sensory organs, as well as the neurons that form the cochleovestibular ganglion (CVG. The molecular dynamics that occur at the NSD boundary relative to adjacent OV cells is not well defined. The Tbx1 transcription factor gene expression pattern is complementary to the NSD, and inactivation results in expansion of the NSD and expression of the Notch ligand, Jag1 mapping, in part of the NSD. To shed light on the role of Jag1 in NSD development, as well as to test whether Tbx1 and Jag1 might genetically interact to regulate this process, we inactivated Jag1 within the Tbx1 expression domain using a knock-in Tbx1Cre allele. We observed an enlarged neurogenic domain marked by a synergistic increase in expression of NeuroD and other proneural transcription factor genes in double Tbx1 and Jag1 conditional loss-of-function embryos. We noted that neuroblasts preferentially expanded across the medial-lateral axis and that an increase in cell proliferation could not account for this expansion, suggesting that there was a change in cell fate. We also found that inactivation of Jag1 with Tbx1Cre resulted in failed development of the cristae and semicircular canals, as well as notably fewer hair cells in the ventral epithelium of the inner ear rudiment when inactivated on a Tbx1 null background, compared to Tbx1Cre/− mutant embryos. We propose that loss of expression of Tbx1 and Jag1 within the Tbx1 expression domain tips the balance of cell fates in the NSD, resulting in an overproduction of neuroblasts at the expense of non-neural cells within the OV.

A Review of Issues Related to Data Acquisition and Analysis in EEG/MEG Studies.

Science.gov (United States)

Puce, Aina; Hämäläinen, Matti S

2017-05-31

Electroencephalography (EEG) and magnetoencephalography (MEG) are non-invasive electrophysiological methods, which record electric potentials and magnetic fields due to electric currents in synchronously-active neurons. With MEG being more sensitive to neural activity from tangential currents and EEG being able to detect both radial and tangential sources, the two methods are complementary. Over the years, neurophysiological studies have changed considerably: high-density recordings are becoming de rigueur; there is interest in both spontaneous and evoked activity; and sophisticated artifact detection and removal methods are available. Improved head models for source estimation have also increased the precision of the current estimates, particularly for EEG and combined EEG/MEG. Because of their complementarity, more investigators are beginning to perform simultaneous EEG/MEG studies to gain more complete information about neural activity. Given the increase in methodological complexity in EEG/MEG, it is important to gather data that are of high quality and that are as artifact free as possible. Here, we discuss some issues in data acquisition and analysis of EEG and MEG data. Practical considerations for different types of EEG and MEG studies are also discussed.

A Review of Issues Related to Data Acquisition and Analysis in EEG/MEG Studies

Directory of Open Access Journals (Sweden)

Aina Puce

2017-05-01

Full Text Available Electroencephalography (EEG and magnetoencephalography (MEG are non-invasive electrophysiological methods, which record electric potentials and magnetic fields due to electric currents in synchronously-active neurons. With MEG being more sensitive to neural activity from tangential currents and EEG being able to detect both radial and tangential sources, the two methods are complementary. Over the years, neurophysiological studies have changed considerably: high-density recordings are becoming de rigueur; there is interest in both spontaneous and evoked activity; and sophisticated artifact detection and removal methods are available. Improved head models for source estimation have also increased the precision of the current estimates, particularly for EEG and combined EEG/MEG. Because of their complementarity, more investigators are beginning to perform simultaneous EEG/MEG studies to gain more complete information about neural activity. Given the increase in methodological complexity in EEG/MEG, it is important to gather data that are of high quality and that are as artifact free as possible. Here, we discuss some issues in data acquisition and analysis of EEG and MEG data. Practical considerations for different types of EEG and MEG studies are also discussed.

Modeling bistable cell-fate choices in the Drosophila eye: qualitative and quantitative perspectives

Science.gov (United States)

Graham, Thomas G. W.; Tabei, S. M. Ali; Dinner, Aaron R.; Rebay, Ilaria

2010-01-01

A major goal of developmental biology is to understand the molecular mechanisms whereby genetic signaling networks establish and maintain distinct cell types within multicellular organisms. Here, we review cell-fate decisions in the developing eye of Drosophila melanogaster and the experimental results that have revealed the topology of the underlying signaling circuitries. We then propose that switch-like network motifs based on positive feedback play a central role in cell-fate choice, and discuss how mathematical modeling can be used to understand and predict the bistable or multistable behavior of such networks. PMID:20570936

Multipotency of Adult Hippocampal NSCs In Vivo Is Restricted by Drosha/NFIB.

Science.gov (United States)

Rolando, Chiara; Erni, Andrea; Grison, Alice; Beattie, Robert; Engler, Anna; Gokhale, Paul J; Milo, Marta; Wegleiter, Thomas; Jessberger, Sebastian; Taylor, Verdon

2016-11-03

Adult neural stem cells (NSCs) are defined by their inherent capacity to self-renew and give rise to neurons, astrocytes, and oligodendrocytes. In vivo, however, hippocampal NSCs do not generate oligodendrocytes for reasons that have remained enigmatic. Here, we report that deletion of Drosha in adult dentate gyrus NSCs activates oligodendrogenesis and reduces neurogenesis at the expense of gliogenesis. We further find that Drosha directly targets NFIB to repress its expression independently of Dicer and microRNAs. Knockdown of NFIB in Drosha-deficient hippocampal NSCs restores neurogenesis, suggesting that the Drosha/NFIB mechanism robustly prevents oligodendrocyte fate acquisition in vivo. Taken together, our findings establish that adult hippocampal NSCs inherently possess multilineage potential but that Drosha functions as a molecular barrier preventing oligodendrogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Making fate and exposure models for freshwater ecotoxicity in life cycle assessment suitable for organic acids and bases.

Science.gov (United States)

van Zelm, Rosalie; Stam, Gea; Huijbregts, Mark A J; van de Meent, Dik

2013-01-01

Freshwater fate and exposure factors were determined for organic acids and bases, making use of the knowledge on electrical interaction of ionizing chemicals and their sorption to particles. The fate factor represents the residence time in the environment whereas exposure factors equal the dissolved fraction of a chemical. Multimedia fate, exposure, and effect model USES-LCA was updated to take into account the influence of ionization, based upon the acid dissociation constant (pK(a)) of a chemical, and the environmental pH. Freshwater fate (FF) and exposure (XF) factors were determined for 415 acids and 496 bases emitted to freshwater, air, and soil. The relevance of taking account of the degree of ionization of chemicals was tested by determining the ratio (R) of the new vs. fate and exposure factors determined with USES-LCA suitable for neutral chemicals only. Our results show that the majority of freshwater fate and exposure factors of chemicals that are largely ionized in the environment are larger with the ionics model compared to the factors determined with the neutrals model version. R(FF) ranged from 2.4×10(-1) to 1.6×10(1) for freshwater emissions, from 1.2×10(-2) to 2.0×10(4) for soil emissions and from 5.8×10(-2) to 6.0×10(3) for air emissions, and R(XF) from 5.3×10(-1) to 2.2×10(1). Prediction of changed solid-water partitioning, implying a change in runoff and in removal via sedimentation, and prediction of negligible air-water partition coefficient, leading to negligible volatilization were the main contributors to the changes in freshwater fate factors. Copyright © 2012 Elsevier Ltd. All rights reserved.

Fate of pesticides in field ditches: the TOXSWA simulation model

NARCIS (Netherlands)

Adriaanse, P.I.

1996-01-01

The TOXSWA model describes the fate of pesticides entering field ditches by spray drift, atmospheric deposition, surface run-off, drainage or leaching. It considers four processes: transport, transformation, sorption and volatilization. Analytical andnumerical solutions corresponded well. A sample

Fate of Salmonella Typhimurium in laboratory-scale drinking water biofilms

CSIR Research Space (South Africa)

Schaefer, Lisa M

2013-08-01

Full Text Available biofilms in monoculture and the fate and persistence of Salmonella in a mixed aquatic biofilm was examined. In monoculture S. Typhimurium formed loosely structured biofilms. Salmonella colonized established multi-species drinking water biofilms within 24...

48 CFR 307.104-70 - Acquisition strategy.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Acquisition strategy. 307... AND ACQUISITION PLANNING ACQUISITION PLANNING Acquisition Planning 307.104-70 Acquisition strategy... designated by the HHS CIO, DASFMP, the CAO, or the cognizant HCA) shall prepare an acquisition strategy using...

Neural networks for aircraft control

Science.gov (United States)

Linse, Dennis

1990-01-01

Current research in Artificial Neural Networks indicates that networks offer some potential advantages in adaptation and fault tolerance. This research is directed at determining the possible applicability of neural networks to aircraft control. The first application will be to aircraft trim. Neural network node characteristics, network topology and operation, neural network learning and example histories using neighboring optimal control with a neural net are discussed.

Fates of Chemical Elements in Biomass during Its Pyrolysis.

Science.gov (United States)

Liu, Wu-Jun; Li, Wen-Wei; Jiang, Hong; Yu, Han-Qing

2017-05-10

Biomass is increasingly perceived as a renewable resource rather than as an organic solid waste today, as it can be converted to various chemicals, biofuels, and solid biochar using modern processes. In the past few years, pyrolysis has attracted growing interest as a promising versatile platform to convert biomass into valuable resources. However, an efficient and selective conversion process is still difficult to be realized due to the complex nature of biomass, which usually makes the products complicated. Furthermore, various contaminants and inorganic elements (e.g., heavy metals, nitrogen, phosphorus, sulfur, and chlorine) embodied in biomass may be transferred into pyrolysis products or released into the environment, arousing environmental pollution concerns. Understanding their behaviors in biomass pyrolysis is essential to optimizing the pyrolysis process for efficient resource recovery and less environmental pollution. However, there is no comprehensive review so far about the fates of chemical elements in biomass during its pyrolysis. Here, we provide a critical review about the fates of main chemical elements (C, H, O, N, P, Cl, S, and metals) in biomass during its pyrolysis. We overview the research advances about the emission, transformation, and distribution of elements in biomass pyrolysis, discuss the present challenges for resource-oriented conversion and pollution abatement, highlight the importance and significance of understanding the fate of elements during pyrolysis, and outlook the future development directions for process control. The review provides useful information for developing sustainable biomass pyrolysis processes with an improved efficiency and selectivity as well as minimized environmental impacts, and encourages more research efforts from the scientific communities of chemistry, the environment, and energy.

Fate and transport of pathogens in lakes and reservoirs.

Science.gov (United States)

Brookes, Justin D; Antenucci, Jason; Hipsey, Matthew; Burch, Michael D; Ashbolt, Nicholas J; Ferguson, Christobel

2004-07-01

Outbreaks of water-borne disease via public water supplies continue to be reported in developed countries even though there is increased awareness of, and treatment for, pathogen contamination. Pathogen episodes in lakes and reservoirs are often associated with rain events, and the riverine inflow is considered to be major source of pathogens. Consequently, the behaviour of these inflows is of particular importance in determining pathogen transport and distribution. Inflows are controlled by their density relative to that of the lake, such that warm inflows will flow over the surface of the lake as a buoyant surface flow and cold, dense inflows will sink beneath the lake water where they will flow along the bathymetry towards the deepest point. The fate of pathogens is determined by loss processes including settling and inactivation by temperature, UV and grazing. The general trend is for the insertion timescale to be shortest, followed by sedimentation losses and temperature inactivity. The fate of Cryptosporidium due to UV light inactivation can occur at opposite ends of the scale, depending on the location of the oocysts in the water column and the extinction coefficient for UV light. For this reason, the extinction coefficient for UV light appears to be a vitally important parameter for determining the risk of Cryptosporidium contamination. For risk assessment of pathogens in supply reservoirs, it is important to understand the role of hydrodynamics in determining the timescale of transport to the off-take relative to the timescale of inactivation. The characteristics of the riverine intrusion must also be considered when designing a sampling program for pathogens. A risk management framework is presented that accounts for pathogen fate and transport for reservoirs.

Simulation of Reactive Constituent Fate and Transport in Hydrologic Simulator GSSHA

National Research Council Canada - National Science Library

Downer, Charles W

2009-01-01

The purpose of this System-Wide Water Resources Program (SWWRP) technical note is to describe the new fate and transport routines in the Gridded Surface Subsurface Hydrologic Analysis (GSSHA) model...

Development of social skills in children: neural and behavioral evidence for the elaboration of cognitive models

Science.gov (United States)

Soto-Icaza, Patricia; Aboitiz, Francisco; Billeke, Pablo

2015-01-01

Social skills refer to a wide group of abilities that allow us to interact and communicate with others. Children learn how to solve social situations by predicting and understanding other's behaviors. The way in which humans learn to interact successfully with others encompasses a complex interaction between neural, behavioral, and environmental elements. These have a role in the accomplishment of positive developmental outcomes, including peer acceptance, academic achievement, and mental health. All these social abilities depend on widespread brain networks that are recently being studied by neuroscience. In this paper, we will first review the studies on this topic, aiming to clarify the behavioral and neural mechanisms related to the acquisition of social skills during infancy and their appearance in time. Second, we will briefly describe how developmental diseases like Autism Spectrum Disorders (ASD) can inform about the neurobiological mechanisms of social skills. We finally sketch a general framework for the elaboration of cognitive models in order to facilitate the comprehension of human social development. PMID:26483621

The Neural Border: Induction, Specification and Maturation of the territory that generates Neural Crest cells.

Science.gov (United States)

Pla, Patrick; Monsoro-Burq, Anne H

2018-05-28

The neural crest is induced at the edge between the neural plate and the nonneural ectoderm, in an area called the neural (plate) border, during gastrulation and neurulation. In recent years, many studies have explored how this domain is patterned, and how the neural crest is induced within this territory, that also participates to the prospective dorsal neural tube, the dorsalmost nonneural ectoderm, as well as placode derivatives in the anterior area. This review highlights the tissue interactions, the cell-cell signaling and the molecular mechanisms involved in this dynamic spatiotemporal patterning, resulting in the induction of the premigratory neural crest. Collectively, these studies allow building a complex neural border and early neural crest gene regulatory network, mostly composed by transcriptional regulations but also, more recently, including novel signaling interactions. Copyright © 2018. Published by Elsevier Inc.

Artificial Neural Networks to Predict the Power Output of a PV Panel

Directory of Open Access Journals (Sweden)

Valerio Lo Brano

2014-01-01

Full Text Available The paper illustrates an adaptive approach based on different topologies of artificial neural networks (ANNs for the power energy output forecasting of photovoltaic (PV modules. The analysis of the PV module’s power output needed detailed local climate data, which was collected by a dedicated weather monitoring system. The Department of Energy, Information Engineering, and Mathematical Models of the University of Palermo (Italy has built up a weather monitoring system that worked together with a data acquisition system. The power output forecast is obtained using three different types of ANNs: a one hidden layer Multilayer perceptron (MLP, a recursive neural network (RNN, and a gamma memory (GM trained with the back propagation. In order to investigate the influence of climate variability on the electricity production, the ANNs were trained using weather data (air temperature, solar irradiance, and wind speed along with historical power output data available for the two test modules. The model validation was performed by comparing model predictions with power output data that were not used for the network's training. The results obtained bear out the suitability of the adopted methodology for the short-term power output forecasting problem and identified the best topology.

Fate and transformation of graphene oxide in marine systems

Science.gov (United States)

Graphene oxide (GO) may be released into natural waters at different phases of its life cycle. Currently, there is no study on the fate of GO in seawater, which is predicted to be a major sink for many engineered nanomaterials. In this study, the influences of salinity (0-50 &per...

Evaluating the fate of organic compounds in the Cameroon ...

African Journals Online (AJOL)

Furthermore, a sensitivity analysis was performed to identify the key input parameters. Model simulations indicated significant differences in the fate of the chemicals that could be explained by the variation in physical-chemical properties. The log KOW, emission rate to water (EW), volume of the water compartment (VW) and ...

Transcriptional control of stem cell fate by E2Fs and pocket proteins

Science.gov (United States)

Julian, Lisa M.; Blais, Alexandre

2015-01-01

E2F transcription factors and their regulatory partners, the pocket proteins (PPs), have emerged as essential regulators of stem cell fate control in a number of lineages. In mammals, this role extends from both pluripotent stem cells to those encompassing all embryonic germ layers, as well as extra-embryonic lineages. E2F/PP-mediated regulation of stem cell decisions is highly evolutionarily conserved, and is likely a pivotal biological mechanism underlying stem cell homeostasis. This has immense implications for organismal development, tissue maintenance, and regeneration. In this article, we discuss the roles of E2F factors and PPs in stem cell populations, focusing on mammalian systems. We discuss emerging findings that position the E2F and PP families as widespread and dynamic epigenetic regulators of cell fate decisions. Additionally, we focus on the ever expanding landscape of E2F/PP target genes, and explore the possibility that E2Fs are not simply regulators of general ‘multi-purpose’ cell fate genes but can execute tissue- and cell type-specific gene regulatory programs. PMID:25972892

Transcriptional control of stem cell fate by E2Fs and Pocket Proteins

Directory of Open Access Journals (Sweden)

Lisa Marie Julian

2015-04-01

Full Text Available E2F transcription factors and their regulatory partners, the pocket proteins (PPs, have emerged as essential regulators of stem cell fate control in a number of lineages. In mammals, this role extends from both pluripotent stem cells to those encompassing all embryonic germ layers, as well as extra-embryonic lineages. E2F/PP-mediated regulation of stem cell decisions is highly evolutionarily conserved, and is likely a pivotal biological mechanism underlying stem cell homeostasis. This has immense implications for organismal development, tissue maintenance and regeneration. In this article, we discuss the roles of E2F factors and PPs in stem cell populations, focusing on mammalian systems. We discuss emerging findings that position the E2F and PP families as widespread and dynamic epigenetic regulators of cell fate decisions. Additionally, we focus on the ever expanding landscape of E2F/PP target genes, and explore the possibility that E2Fs are not simply regulators of general ‘multi-purpose’ cell fate genes but can execute tissue- and cell type-specific gene regulatory programs.

Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments

Energy Technology Data Exchange (ETDEWEB)

LaBarge, Mark A; Nelson, Celeste M; Villadsen, Rene; Fridriksdottir, Agla; Ruth, Jason R; Stampfer, Martha R; Petersen, Ole W; Bissell, Mina J

2008-09-19

In adult tissues, multi-potent progenitor cells are some of the most primitive members of the developmental hierarchies that maintain homeostasis. That progenitors and their more mature progeny share identical genomes, suggests that fate decisions are directed by interactions with extrinsic soluble factors, ECM, and other cells, as well as physical properties of the ECM. To understand regulation of fate decisions, therefore, would require a means of understanding carefully choreographed combinatorial interactions. Here we used microenvironment protein microarrays to functionally identify combinations of cell-extrinsic mammary gland proteins and ECM molecules that imposed specific cell fates on bipotent human mammary progenitor cells. Micropatterned cell culture surfaces were fabricated to distinguish between the instructive effects of cell-cell versus cell-ECM interactions, as well as constellations of signaling molecules; and these were used in conjunction with physiologically relevant 3 dimensional human breast cultures. Both immortalized and primary human breast progenitors were analyzed. We report on the functional ability of those proteins of the mammary gland that maintain quiescence, maintain the progenitor state, and guide progenitor differentiation towards myoepithelial and luminal lineages.

Large-scale electrophysiology: acquisition, compression, encryption, and storage of big data.

Science.gov (United States)

Brinkmann, Benjamin H; Bower, Mark R; Stengel, Keith A; Worrell, Gregory A; Stead, Matt

2009-05-30

The use of large-scale electrophysiology to obtain high spatiotemporal resolution brain recordings (>100 channels) capable of probing the range of neural activity from local field potential oscillations to single-neuron action potentials presents new challenges for data acquisition, storage, and analysis. Our group is currently performing continuous, long-term electrophysiological recordings in human subjects undergoing evaluation for epilepsy surgery using hybrid intracranial electrodes composed of up to 320 micro- and clinical macroelectrode arrays. DC-capable amplifiers, sampling at 32kHz per channel with 18-bits of A/D resolution are capable of resolving extracellular voltages spanning single-neuron action potentials, high frequency oscillations, and high amplitude ultra-slow activity, but this approach generates 3 terabytes of data per day (at 4 bytes per sample) using current data formats. Data compression can provide several practical benefits, but only if data can be compressed and appended to files in real-time in a format that allows random access to data segments of varying size. Here we describe a state-of-the-art, scalable, electrophysiology platform designed for acquisition, compression, encryption, and storage of large-scale data. Data are stored in a file format that incorporates lossless data compression using range-encoded differences, a 32-bit cyclically redundant checksum to ensure data integrity, and 128-bit encryption for protection of patient information.

[First language acquisition research and theories of language acquisition].

Science.gov (United States)

Miller, S; Jungheim, M; Ptok, M

2014-04-01

In principle, a child can seemingly easily acquire any given language. First language acquisition follows a certain pattern which to some extent is found to be language independent. Since time immemorial, it has been of interest why children are able to acquire language so easily. Different disciplinary and methodological orientations addressing this question can be identified. A selective literature search in PubMed and Scopus was carried out and relevant monographies were considered. Different, partially overlapping phases can be distinguished in language acquisition research: whereas in ancient times, deprivation experiments were carried out to discover the "original human language", the era of diary studies began in the mid-19th century. From the mid-1920s onwards, behaviouristic paradigms dominated this field of research; interests were focussed on the determination of normal, average language acquisition. The subsequent linguistic period was strongly influenced by the nativist view of Chomsky and the constructivist concepts of Piaget. Speech comprehension, the role of speech input and the relevance of genetic disposition became the centre of attention. The interactionist concept led to a revival of the convergence theory according to Stern. Each of these four major theories--behaviourism, cognitivism, interactionism and nativism--have given valuable and unique impulses, but no single theory is universally accepted to provide an explanation of all aspects of language acquisition. Moreover, it can be critically questioned whether clinicians consciously refer to one of these theories in daily routine work and whether therapies are then based on this concept. It remains to be seen whether or not new theories of grammar, such as the so-called construction grammar (CxG), will eventually change the general concept of language acquisition.

Neural network regulation driven by autonomous neural firings

Science.gov (United States)

Cho, Myoung Won

2016-07-01

Biological neurons naturally fire spontaneously due to the existence of a noisy current. Such autonomous firings may provide a driving force for network formation because synaptic connections can be modified due to neural firings. Here, we study the effect of autonomous firings on network formation. For the temporally asymmetric Hebbian learning, bidirectional connections lose their balance easily and become unidirectional ones. Defining the difference between reciprocal connections as new variables, we could express the learning dynamics as if Ising model spins interact with each other in magnetism. We present a theoretical method to estimate the interaction between the new variables in a neural system. We apply the method to some network systems and find some tendencies of autonomous neural network regulation.

Explanation of the degree of Divine Knowledge in the degree of Decrees of fate in Molla Sadra and Allama Tabatabai\\\\\\'s views

Directory of Open Access Journals (Sweden)

Alireza Khajegir

2013-09-01

Full Text Available The Sadraee's transcendental philosophy in theology affected by the authentic Divinity texts and discussions and has inspired in resolving many of the theological and philosophical problems of this school. Therefore, this school can be considered as the most prominent school. Although, Molla sadra does not know enough the argument and arguing without conscience and purification of self, but, the most based on imported sources of revelation and interpretations of Imams (AS and believes that truths of faith are not possible except by purifying heart from the whims, thinking of the Divine verses, hadith of the Prophet (The Prophet's massage and his tribe, and following the way of the pious men. Proposing the problem of Divine Decrees of fate in transcendental philosophy and explaining its principles that brought up in both the philosophical texts and exegesis of the followers of transcendental philosophy are of the most important Instances that this school takes impression from religious texts.    Decrees of fate has various levels,  such as essential and actual, scientific and objective, divine creation and divine legislation, fixed and variable, that is every level take into consideration the discussion of Divine Decrees of fate from a particular direction. Divine Decrees of fate in one dimension is related to the degrees of Divine knowledge and the quality of Divine knowledge on what is apart from God, on the other dimension, is related to the question of the necessity of The existence system and the quality of causal connection between the elements of the universe and the origin of necessity of The existence system that has been expressed in these schools with a certain thoughtfulness in both theology and cosmology. Divine Decrees of fate in comparing with universal realms of existence is considered the same as degree of intellectual forms beyond the spiritual and natural forms that emanated from the god, suddenly and timelessly and called

Design of the M&S acquisition support effort of the SANDF GBADS acquisition programme

CSIR Research Space (South Africa)

Nel, JJ

2007-06-01

Full Text Available (AmADS) GBADS Phase 2 (MobADS) GBADS Phase 3 (LmADS) GBADS Phase 4 (C2 Optimisation) GBADS Phase 5 (MecADS) Figure 1: GBADS Phased Acquisition. The acquisition programme comprises five phases each addressing the acquisition of a specific... element of the GBADS. Phase 1 addresses an Air-mobile Air Defence System (AmADS) utilising man-portable missiles that can also be employed as a component of a Mobile Air Defence System (MobADS). Phase 2 involves the acquisition of the remainder...

Circadian Clock Genes Are Essential for Normal Adult Neurogenesis, Differentiation, and Fate Determination.

Directory of Open Access Journals (Sweden)

Astha Malik

proliferation during differentiation, but they generated normal percentages of neuronal cells. Neuronal fate commitment therefore appears to be controlled through a non-clock function of BMAL1. This study provides insight into how cell autonomous circadian clocks and clock genes regulate adult neural stem cells with implications for treating neurodegenerative disorders and impaired brain functions by manipulating neurogenesis.

Dynamics of neural cryptography.

Science.gov (United States)

Ruttor, Andreas; Kinzel, Wolfgang; Kanter, Ido

2007-05-01

Synchronization of neural networks has been used for public channel protocols in cryptography. In the case of tree parity machines the dynamics of both bidirectional synchronization and unidirectional learning is driven by attractive and repulsive stochastic forces. Thus it can be described well by a random walk model for the overlap between participating neural networks. For that purpose transition probabilities and scaling laws for the step sizes are derived analytically. Both these calculations as well as numerical simulations show that bidirectional interaction leads to full synchronization on average. In contrast, successful learning is only possible by means of fluctuations. Consequently, synchronization is much faster than learning, which is essential for the security of the neural key-exchange protocol. However, this qualitative difference between bidirectional and unidirectional interaction vanishes if tree parity machines with more than three hidden units are used, so that those neural networks are not suitable for neural cryptography. In addition, the effective number of keys which can be generated by the neural key-exchange protocol is calculated using the entropy of the weight distribution. As this quantity increases exponentially with the system size, brute-force attacks on neural cryptography can easily be made unfeasible.

Dynamics of neural cryptography

International Nuclear Information System (INIS)

Ruttor, Andreas; Kinzel, Wolfgang; Kanter, Ido

2007-01-01

Synchronization of neural networks has been used for public channel protocols in cryptography. In the case of tree parity machines the dynamics of both bidirectional synchronization and unidirectional learning is driven by attractive and repulsive stochastic forces. Thus it can be described well by a random walk model for the overlap between participating neural networks. For that purpose transition probabilities and scaling laws for the step sizes are derived analytically. Both these calculations as well as numerical simulations show that bidirectional interaction leads to full synchronization on average. In contrast, successful learning is only possible by means of fluctuations. Consequently, synchronization is much faster than learning, which is essential for the security of the neural key-exchange protocol. However, this qualitative difference between bidirectional and unidirectional interaction vanishes if tree parity machines with more than three hidden units are used, so that those neural networks are not suitable for neural cryptography. In addition, the effective number of keys which can be generated by the neural key-exchange protocol is calculated using the entropy of the weight distribution. As this quantity increases exponentially with the system size, brute-force attacks on neural cryptography can easily be made unfeasible

Dynamics of neural cryptography

Science.gov (United States)

Ruttor, Andreas; Kinzel, Wolfgang; Kanter, Ido

2007-05-01

Synchronization of neural networks has been used for public channel protocols in cryptography. In the case of tree parity machines the dynamics of both bidirectional synchronization and unidirectional learning is driven by attractive and repulsive stochastic forces. Thus it can be described well by a random walk model for the overlap between participating neural networks. For that purpose transition probabilities and scaling laws for the step sizes are derived analytically. Both these calculations as well as numerical simulations show that bidirectional interaction leads to full synchronization on average. In contrast, successful learning is only possible by means of fluctuations. Consequently, synchronization is much faster than learning, which is essential for the security of the neural key-exchange protocol. However, this qualitative difference between bidirectional and unidirectional interaction vanishes if tree parity machines with more than three hidden units are used, so that those neural networks are not suitable for neural cryptography. In addition, the effective number of keys which can be generated by the neural key-exchange protocol is calculated using the entropy of the weight distribution. As this quantity increases exponentially with the system size, brute-force attacks on neural cryptography can easily be made unfeasible.

Classifying magnetic resonance image modalities with convolutional neural networks

Science.gov (United States)

Remedios, Samuel; Pham, Dzung L.; Butman, John A.; Roy, Snehashis

2018-02-01

Magnetic Resonance (MR) imaging allows the acquisition of images with different contrast properties depending on the acquisition protocol and the magnetic properties of tissues. Many MR brain image processing techniques, such as tissue segmentation, require multiple MR contrasts as inputs, and each contrast is treated differently. Thus it is advantageous to automate the identification of image contrasts for various purposes, such as facilitating image processing pipelines, and managing and maintaining large databases via content-based image retrieval (CBIR). Most automated CBIR techniques focus on a two-step process: extracting features from data and classifying the image based on these features. We present a novel 3D deep convolutional neural network (CNN)- based method for MR image contrast classification. The proposed CNN automatically identifies the MR contrast of an input brain image volume. Specifically, we explored three classification problems: (1) identify T1-weighted (T1-w), T2-weighted (T2-w), and fluid-attenuated inversion recovery (FLAIR) contrasts, (2) identify pre vs postcontrast T1, (3) identify pre vs post-contrast FLAIR. A total of 3418 image volumes acquired from multiple sites and multiple scanners were used. To evaluate each task, the proposed model was trained on 2137 images and tested on the remaining 1281 images. Results showed that image volumes were correctly classified with 97.57% accuracy.

Watch Out for the “Living Dead”: Cell-Free Enzymes and Their Fate

Directory of Open Access Journals (Sweden)

Federico Baltar

2018-01-01

Full Text Available Microbes are the engines driving biogeochemical cycles. Microbial extracellular enzymatic activities (EEAs are the “gatekeepers” of the carbon cycle. The total EEA is the sum of cell-bound (i.e., cell-attached, and dissolved (i.e., cell-free enzyme activities. Cell-free enzymes make up a substantial proportion (up to 100% of the total marine EEA. Although we are learning more about how microbial diversity and function (including total EEA will be affected by environmental changes, little is known about what factors control the importance of the abundant cell-free enzymes. Since cell-attached EEAs are linked to the cell, their fate will likely be linked to the factors controlling the cell’s fate. In contrast, cell-free enzymes belong to a kind of “living dead” realm because they are not attached to a living cell but still are able to perform their function away from the cell; and as such, the factors controlling their activity and fate might differ from those affecting cell-attached enzymes. This article aims to place cell-free EEA into the wider context of hydrolysis of organic matter, deal with recent studies assessing what controls the production, activity and lifetime of cell-free EEA, and what their fate might be in response to environmental stressors. This perspective article advocates the need to go “beyond the living things,” studying the response of cells/organisms to different stressors, but also to study cell-free enzymes, in order to fully constrain the future and evolution of marine biogeochemical cycles.

Watch Out for the “Living Dead”: Cell-Free Enzymes and Their Fate

Science.gov (United States)

Baltar, Federico

2018-01-01

Microbes are the engines driving biogeochemical cycles. Microbial extracellular enzymatic activities (EEAs) are the “gatekeepers” of the carbon cycle. The total EEA is the sum of cell-bound (i.e., cell-attached), and dissolved (i.e., cell-free) enzyme activities. Cell-free enzymes make up a substantial proportion (up to 100%) of the total marine EEA. Although we are learning more about how microbial diversity and function (including total EEA) will be affected by environmental changes, little is known about what factors control the importance of the abundant cell-free enzymes. Since cell-attached EEAs are linked to the cell, their fate will likely be linked to the factors controlling the cell’s fate. In contrast, cell-free enzymes belong to a kind of “living dead” realm because they are not attached to a living cell but still are able to perform their function away from the cell; and as such, the factors controlling their activity and fate might differ from those affecting cell-attached enzymes. This article aims to place cell-free EEA into the wider context of hydrolysis of organic matter, deal with recent studies assessing what controls the production, activity and lifetime of cell-free EEA, and what their fate might be in response to environmental stressors. This perspective article advocates the need to go “beyond the living things,” studying the response of cells/organisms to different stressors, but also to study cell-free enzymes, in order to fully constrain the future and evolution of marine biogeochemical cycles. PMID:29354095

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.

Promoted neuronal differentiation after activation of alpha4/beta2 nicotinic acetylcholine receptors in undifferentiated neural progenitors.

Directory of Open Access Journals (Sweden)

Takeshi Takarada

defective of NMDA receptor subunit-1, nicotine was still effective in significantly inhibiting the proliferation. CONCLUSIONS/SIGNIFICANCE: Functional α4β2 nAChR subtype would be constitutively expressed to play a role in the mechanism underlying the determination of proliferation and subsequent differentiation fate into a neuronal lineage in association with preferential promotion of Math1 expression in undifferentiated neural progenitors of developing rodent neocortex independently of NMDA receptor activation.

Stem Cell Fate Determination during Development and Regeneration of Ectodermal Organs

Science.gov (United States)

Jiménez-Rojo, Lucía; Granchi, Zoraide; Graf, Daniel; Mitsiadis, Thimios A.

2012-01-01

The development of ectoderm-derived appendages results in a large variety of highly specialized organs such as hair follicles, mammary glands, salivary glands, and teeth. Despite varying in number, shape, and function, all these ectodermal organs develop through continuous and reciprocal epithelial–mesenchymal interactions, sharing common morphological and molecular features especially during their embryonic development. Diseases such as ectodermal dysplasias can affect simultaneously these organs, suggesting that they may arise from common multipotent precursors residing in the embryonic ectoderm. During embryogenesis, these putative ectodermal stem cells may adopt different fates and consequently be able to generate a variety of tissue-specific stem cells, which are the sources for the various cell lineages that form the diverse organs. The specification of those common epithelial precursors, as well as their further lineage commitment to tissue-specific stem cells, might be controlled by specific signals. It has been well documented that Notch, Wnt, bone morphogenetic protein, and fibroblast growth factor signaling pathways regulate cell fate decisions during the various stages of ectodermal organ development. However, the in vivo spatial and temporal dynamics of these signaling pathways are not yet well understood. Improving the current knowledge on the mechanisms involved in stem cell fate determination during organogenesis and homeostasis of ectodermal organs is crucial to develop effective stem cell-based therapies in order to regenerate or replace pathological and damaged tissues. PMID:22539926

Diversity among POU transcription factors in chromatin recognition and cell fate reprogramming.

Science.gov (United States)

Malik, Vikas; Zimmer, Dennis; Jauch, Ralf

2018-05-01

The POU (Pit-Oct-Unc) protein family is an evolutionary ancient group of transcription factors (TFs) that bind specific DNA sequences to direct gene expression programs. The fundamental importance of POU TFs to orchestrate embryonic development and to direct cellular fate decisions is well established, but the molecular basis for this activity is insufficiently understood. POU TFs possess a bipartite 'two-in-one' DNA binding domain consisting of two independently folding structural units connected by a poorly conserved and flexible linker. Therefore, they represent a paradigmatic example to study the molecular basis for the functional versatility of TFs. Their modular architecture endows POU TFs with the capacity to accommodate alternative composite DNA sequences by adopting different quaternary structures. Moreover, associations with partner proteins crucially influence the selection of their DNA binding sites. The plentitude of DNA binding modes confers the ability to POU TFs to regulate distinct genes in the context of different cellular environments. Likewise, different binding modes of POU proteins to DNA could trigger alternative regulatory responses in the context of different genomic locations of the same cell. Prominent POU TFs such as Oct4, Brn2, Oct6 and Brn4 are not only essential regulators of development but have also been successfully employed to reprogram somatic cells to pluripotency and neural lineages. Here we review biochemical, structural, genomic and cellular reprogramming studies to examine how the ability of POU TFs to select regulatory DNA, alone or with partner factors, is tied to their capacity to epigenetically remodel chromatin and drive specific regulatory programs that give cells their identities.

IT-based Value Creation in Serial Acquisitions

DEFF Research Database (Denmark)

Henningsson, Stefan; Yetton, Philip

2013-01-01

serial acquirers realize IT-based value, we integrate and model the findings on individual acquisitions from the extant literature, and extend that model to explain the effects of sequential acquisitions in a growth-by-acquisition strategy. This extended model, drawing on the Resource-Based Theory......The extant research on post-acquisition IT integration analyzes how acquirers realize IT-based value in individual acquisitions. However, serial acquirers make 60% of acquisitions. These acquisitions are not isolated events, but are components in growth-by-acquisition programs. To explain how...

48 CFR 970.2301 - Sustainable acquisition.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Sustainable acquisition. 970.2301 Section 970.2301 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY..., Renewable Energy Technologies, Occupational Safety and Drug-Free Work Place 970.2301 Sustainable acquisition...

Influences of aquatic plants on the fate of the pyrethroid insecticide lambda-cyhalothrin in aquatic environments.

Science.gov (United States)

Hand, L H; Kuet, S F; Lane, M C; Maund, S J; Warinton, J S; Hill, I R

2001-08-01

Aquatic exposure assessments for pesticides are generally based on laboratory studies performed in water alone or water sediment systems. Although aquatic macrophytes, which include a variety of bryophytes, macroalgae, and angiosperms, can be a significant component of many aquatic ecosystems, their impact on pesticide fate is generally not included in exposure assessments. To investigate the influence of aquatic plants on the fate and behavior of the pyrethroid insecticide lambda (lambda)-cyhalothrin, two laboratory experiments (to assess adsorption and degradation) and an indoor microcosm study (to assess fate under semirealistic conditions) were conducted. In the laboratory studies, adsorption to macrophytes was extensive and essentially irreversible, and degradation occurred rapidly by cleavage of the ester bond. In the indoor microcosm, which contained water, sediment, and macrophytes from a pond, degradation was also rapid, with DT50 and DT90 values of less than 3 and 19 h, respectively, for dissipation from the water column and of less than 3 and 56 h, respectively, for the whole system. For adsorptive and readily degraded pesticides like lambda-cyhalothrin, we conclude that macrophytes have considerable influence on fate and behavior in surface waters.

Acquisitions by EMNCs in Developed Markets

DEFF Research Database (Denmark)

Rabbiosi, Larissa; Elia, Stefano; Bertoni, Fabio

2012-01-01

Building on an organisational learning perspective, we argue that emerging market firms’ international experience and home-country characteristics are core sources of learning. Furthermore, we argue that these factors constitute important determinants of emerging market firms’ acquisition behaviour...... in developed countries (south-north acquisitions). We test our hypotheses on a sample of 808 south-north acquisitions. The acquisitions were undertaken in Europe, Japan and North America (Canada and the US) between 1999 and 2008 by firms from the emerging economies of Brazil, Russia, India and China....... As suggested by the internationalisation process model, our results show that emerging market firms undertake acquisitions in developed countries in an incremental fashion. Acquisition experience in developed markets increases the likelihood of exploitative expansion, while acquisition experience in developing...

Improving Acquisition Outcomes with Contextual Ambidexterity

DEFF Research Database (Denmark)

Meglio, Olimpia; King, David R.; Risberg, Annette

2015-01-01

The results of research on mergers and acquisitions often point to a need to improve acquisition outcomes and lessen the organizational turmoil that can often follow integration efforts. We assert that viewing acquisition integration through the lens of contextual ambidexterity may improve...... acquisition outcomes in two ways: by providing an integrated solution to the economic and social tensions in acquisitions, and by enabling managers to effectively confront the competing needs of task and human integration. We also posit that by building on contextual ambidexterity, we can extend...... the possibilities for both research and practice regarding task and human integration in acquisitions. We also emphasize the role of an integration manager and integration mechanisms in enabling contextual ambidexterity for successful acquisition integration. Finally, we identify implications for research...

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.

Environmental Application, Fate, Effects, and Concerns of Ionic Liquids: A Review.

Science.gov (United States)

Amde, Meseret; Liu, Jing-Fu; Pang, Long

2015-11-03

Ionic liquids (ILs) comprise mostly of organic salts with negligible vapor pressure and low flammability that are proposed as replacements for volatile solvents. ILs have been promoted as "green" solvents and widely investigated for their various applications. Although the utility of these chemicals is unquestionable, their toxic effects have attracted great attention. In order to manage their potential hazards and design environmentally benign ILs, understanding their environmental behavior, fate and effects is important. In this review, environmentally relevant issues of ILs, including their environmental application, environmental behavior and toxicity are addressed. In addition, also presented are the influence of ILs on the environmental fate and toxicity of other coexisting contaminants, important routes for designing nontoxic ILs and the techniques that might be adopted for the removal of ILs.

Acquisition of HPLC-Mass Spectrometer

Science.gov (United States)

2015-08-18

31-Jan-2015 Approved for Public Release; Distribution Unlimited Final Report: Acquisition of HPLC -Mass Spectrometer The views, opinions and/or findings...published in peer-reviewed journals: Final Report: Acquisition of HPLC -Mass Spectrometer Report Title The acquisition of the mass spectrometer has been a

Deep Learning Neural Networks and Bayesian Neural Networks in Data Analysis

Directory of Open Access Journals (Sweden)

Chernoded Andrey

2017-01-01

Full Text Available Most of the modern analyses in high energy physics use signal-versus-background classification techniques of machine learning methods and neural networks in particular. Deep learning neural network is the most promising modern technique to separate signal and background and now days can be widely and successfully implemented as a part of physical analysis. In this article we compare Deep learning and Bayesian neural networks application as a classifiers in an instance of top quark analysis.

Photochemical fate of beta-blockers in NOM enriched waters

International Nuclear Information System (INIS)

Wang, Ling; Xu, Haomin; Cooper, William J.; Song, Weihua

2012-01-01

Beta-blockers, prescribed for the treatment of high blood pressure and for long-term use after a heart attack, have been detected in surface and ground waters. This study examines the photochemical fate of three beta-blockers, atenolol, metoprolol, and nadolol. Hydrolysis accounted for minor losses of these beta-blockers in the pH range 4–10. The rate of direct photolysis at pH 7 in a solar simulator varied from 6.1 to 8.9 h −1 at pH 7. However, the addition of a natural organic matter (NOM) isolate enhanced the photochemical loss of all three compounds. Indirect photochemical fate, generally described by reactions with hydroxyl radical (·OH) and singlet oxygen ( 1 ΔO 2 ), and, the direct reaction with the triplet excited state, 3 NOM ⁎ , also varied but collectively appeared to be the major loss factor. Bimolecular reaction rate constants of the three beta-blockers with 1 ΔO 2 and ·OH were measured and accounted for 0.02–0.04% and 7.2–38.9% of their loss, respectively. These data suggest that the 3 NOM ⁎ contributed 50.6–85.4%. Experiments with various 3 NOM ⁎ quenchers supported the hypothesis that it was singly the most important reaction. Atenolol was chosen for more detailed investigation, with the photoproducts identified by LC–MS analysis. The results suggested that electron-transfer could be an important mechanism in photochemical fate of beta-blockers in the presence of NOM. - Highlights: ► Photochemical degradation of beta-blockers in the simulated natural waters. ► Reactive Oxygen Species play a minor role in the indirect photodegradation. ► The loss of beta-blockers results from direct reaction with 3 DOM ⁎ .

Neural Tube Defects

Science.gov (United States)

Neural tube defects are birth defects of the brain, spine, or spinal cord. They happen in the ... that she is pregnant. The two most common neural tube defects are spina bifida and anencephaly. In ...

Cdc20 control of cell fate during prolonged mitotic arrest

DEFF Research Database (Denmark)

Nilsson, Jakob

2011-01-01

The fate of cells arrested in mitosis by antimitotic compounds is complex but is influenced by competition between pathways promoting cell death and pathways promoting mitotic exit. As components of both of these pathways are regulated by Cdc20-dependent degradation, I hypothesize that variations...

Connectivity of the hippocampus and Broca's area during acquisition of a novel grammar.

Science.gov (United States)

Kepinska, Olga; de Rover, Mischa; Caspers, Johanneke; Schiller, Niels O

2018-01-15

Following Opitz and Friederici (2003) suggesting interactions of the hippocampal system and the prefrontal cortex as the neural mechanism underlying novel grammar learning, the present fMRI study investigated functional connectivity of bilateral BA 44/45 and the hippocampus during an artificial grammar learning (AGL) task. Our results, contrary to the previously reported interactions, demonstrated parallel (but separate) contributions of both regions, each with their own interactions, to the process of novel grammar acquisition. The functional connectivity pattern of Broca's area pointed to the importance of coherent activity of left frontal areas around the core language processing region for successful grammar learning. Furthermore, connectivity patterns of left and right hippocampi (predominantly with occipital areas) were found to be a strong predictor of high performance on the task. Finally, increasing functional connectivity over time of both left and right BA 44/45 with the right posterior cingulate cortex and the right temporo-parietal areas points to the importance of multimodal and attentional processes supporting novel grammar acquisition. Moreover, it highlights the right-hemispheric involvement in initial stages of L2 learning. These latter interactions were found to operate irrespective of the task performance, making them an obligatory mechanism accompanying novel grammar learning. Copyright © 2017 Elsevier Inc. All rights reserved.

The Fate of ZnO Nanoparticles Administered to Human Bronchial Epithelial Cells

Science.gov (United States)

Gilbert, Benjamin; Fakra, Sirine C.; Xia, Tian; Pokhrel, Suman; Mädler, Lutz; Nel, André E.

2014-01-01

A particular challenge for nanotoxicology is the evaluation of the biological fate and toxicity of nanomaterials that dissolve in aqueous fluids. Zinc oxide nanomaterials are of particular concern because dissolution leads to release of the toxic divalent zinc ion. Although dissolved zinc ions have been implicated in ZnO cytotoxicity, direct identification of the chemical form of zinc taken up by cells exposed to ZnO nanoparticles, and its intracellular fate, has not yet been achieved. We combined high resolution X-ray spectromicroscopy and high elemental sensitivity X-ray microprobe analyses to determine the fate of ZnO and less soluble iron-doped ZnO nanoparticles following exposure to cultures of human bronchial epithelial cells, BEAS-2B. We complemented two-dimensional X-ray imaging methods with atomic force microscopy of cell surfaces to distinguish between nanoparticles that were transported inside the cells from those that adhered to the cell exterior. The data suggest cellular uptake of ZnO nanoparticles is a mechanism of zinc accumulation in cells. Following uptake, ZnO nanoparticles dissolved completely generating intracellular Zn2+ complexed by molecular ligands. These results corroborate a model for ZnO nanoparticle toxicity that is based on nanoparticle uptake followed by intracellular dissolution. PMID:22646753

Controlling gene networks and cell fate with precision-targeted DNA-binding proteins and small-molecule-based genome readers.

Science.gov (United States)

Eguchi, Asuka; Lee, Garrett O; Wan, Fang; Erwin, Graham S; Ansari, Aseem Z

2014-09-15

Transcription factors control the fate of a cell by regulating the expression of genes and regulatory networks. Recent successes in inducing pluripotency in terminally differentiated cells as well as directing differentiation with natural transcription factors has lent credence to the efforts that aim to direct cell fate with rationally designed transcription factors. Because DNA-binding factors are modular in design, they can be engineered to target specific genomic sequences and perform pre-programmed regulatory functions upon binding. Such precision-tailored factors can serve as molecular tools to reprogramme or differentiate cells in a targeted manner. Using different types of engineered DNA binders, both regulatory transcriptional controls of gene networks, as well as permanent alteration of genomic content, can be implemented to study cell fate decisions. In the present review, we describe the current state of the art in artificial transcription factor design and the exciting prospect of employing artificial DNA-binding factors to manipulate the transcriptional networks as well as epigenetic landscapes that govern cell fate.

Acquisition system for the CLIC Module

CERN Document Server

Vilalte, Sebastien

2011-01-01

The status of R&D activities for CLIC module acquisition are discussed [1]. LAPP is involved in the design of the local CLIC module acquisition crate, described in the document Study of the CLIC Module Front-End Acquisition and Evaluation Electronics [2]. This acquisition system is a project based on a local crate, assigned to the CLIC module, including several mother boards. These motherboards are foreseen to hold mezzanines dedicated to the different subsystems. This system has to work in radiation environment. LAPP is involved in the development of Drive Beam stripline position monitors read-out, described in the document Drive Beam Stripline BPM Electronics and Acquisition [3]. LAPP also develops a generic acquisition mezzanine that allows to perform all-around acquisition and components tests for drive beam stripline BPM read-out.

Neural entrainment to rhythmically-presented auditory, visual and audio-visual speech in children

Directory of Open Access Journals (Sweden)

Alan James Power

2012-07-01

Full Text Available Auditory cortical oscillations have been proposed to play an important role in speech perception. It is suggested that the brain may take temporal ‘samples’ of information from the speech stream at different rates, phase-resetting ongoing oscillations so that they are aligned with similar frequency bands in the input (‘phase locking’. Information from these frequency bands is then bound together for speech perception. To date, there are no explorations of neural phase-locking and entrainment to speech input in children. However, it is clear from studies of language acquisition that infants use both visual speech information and auditory speech information in learning. In order to study neural entrainment to speech in typically-developing children, we use a rhythmic entrainment paradigm (underlying 2 Hz or delta rate based on repetition of the syllable ba, presented in either the auditory modality alone, the visual modality alone, or as auditory-visual speech (via a talking head. To ensure attention to the task, children aged 13 years were asked to press a button as fast as possible when the ba stimulus violated the rhythm for each stream type. Rhythmic violation depended on delaying the occurrence of a ba in the isochronous stream. Neural entrainment was demonstrated for all stream types, and individual differences in standardized measures of language processing were related to auditory entrainment at the theta rate. Further, there was significant modulation of the preferred phase of auditory entrainment in the theta band when visual speech cues were present, indicating cross-modal phase resetting. The rhythmic entrainment paradigm developed here offers a method for exploring individual differences in oscillatory phase locking during development. In particular, a method for assessing neural entrainment and cross-modal phase resetting would be useful for exploring developmental learning difficulties thought to involve temporal sampling

Fate of the synergistic antioxidant system ascorbic acid, lecithin, and tocopherol in mayonnaise: Partion of ascorbic acid

DEFF Research Database (Denmark)

Meyer, Anne Merete Boye; Jacobsen, Charlotte Munch

1996-01-01

Meyer, A. S. & C. Jacobsen, 1996. Fate of the synergistic antioxidant system ascorbic acid, lecithin, and tocopherol in mayonnaise: Partion of ascorbic acid, J. Food Lipids, 3, 139-147.......Meyer, A. S. & C. Jacobsen, 1996. Fate of the synergistic antioxidant system ascorbic acid, lecithin, and tocopherol in mayonnaise: Partion of ascorbic acid, J. Food Lipids, 3, 139-147....

The influence of bedrock hydrogeology on catchment-scale nitrate fate and transport in fractured aquifers

Energy Technology Data Exchange (ETDEWEB)

Orr, Alison [Arup, 50 Ringsend Road, Dublin 4 (Ireland); School of Planning, Architecture and Civil Engineering, Queen' s University Belfast (United Kingdom); Nitsche, Janka [RPS, West Pier Business Campus, Dun Laoghaire, Co. Dublin (Ireland); School of Planning, Architecture and Civil Engineering, Queen' s University Belfast (United Kingdom); Archbold, Marie [School of Planning, Architecture and Civil Engineering, Queen' s University Belfast (United Kingdom); Environmental Protection Agency, Richview, Clonskeagh Road, Dublin 14 (Ireland); Deakin, Jenny [Environmental Protection Agency, Richview, Clonskeagh Road, Dublin 14 (Ireland); Department of Civil, Structural and Environmental Engineering, Trinity College Dublin (Ireland); Ofterdinger, Ulrich; Flynn, Raymond [School of Planning, Architecture and Civil Engineering, Queen' s University Belfast (United Kingdom)

2016-11-01

Characterising catchment scale biogeochemical processes controlling nitrate fate in groundwater constitutes a fundamental consideration when applying programmes of measures to reduce risks posed by diffuse agricultural pollutants to water quality. Combining hydrochemical analyses with nitrate isotopic data and physical hydrogeological measurements permitted characterisation of biogeochemical processes influencing nitrogen fate and transport in the groundwater in two fractured bedrock aquifers with contrasting hydrogeology but comparable nutrient loads. Hydrochemical and isotopic analyses of groundwater samples collected from moderately fractured, diffusely karstified limestone indicated nitrification controlled dissolved nitrogen fate and delivery to aquatic receptors. By contrast nitrate concentrations in groundwater were considerably lower in a low transmissivity highly lithified sandstone and pyrite-bearing shale unit with patchy subsoil cover. Geophysical and hydrochemical investigations showed shallower intervals contained hydraulically active fractures where denitrification was reflected through lower nitrogen levels and an isotopic enrichment ratio of 1.7 between δ{sup 15}N and δ{sup 18}O. Study findings highlight the influence of bedrock hydrogeological conditions on aqueous nitrogen mobility. Investigation results demonstrate that bedrock conditions need to be considered when implementing catchment management plans to reduce the impact of agricultural practices on the quality of groundwater and baseflow in receiving rivers. Nitrate isotopic signatures in the groundwater of a freely draining catchment underlain by a karstified aquifer and a poorly draining aquifer with a low transmissivity aquifer. - Graphical abstract: Contrasting nitrate isotope signatures of groundwater in a free draining catchment underlain by a karstified aquifer and a poorly drained catchment underlain by a low transmissivity aquifer. - Highlights: • Comparison of N fate and

First Language Acquisition and Teaching

Science.gov (United States)

Cruz-Ferreira, Madalena

2011-01-01

"First language acquisition" commonly means the acquisition of a single language in childhood, regardless of the number of languages in a child's natural environment. Language acquisition is variously viewed as predetermined, wondrous, a source of concern, and as developing through formal processes. "First language teaching" concerns schooling in…

Making Acquisition Measurable

Science.gov (United States)

2011-04-30

Corporation. All rights reserved End Users Administrator/ Maintainer (A/M) Subject Matter Expert ( SME ) Trainer/ Instructor Manager, Evaluator, Supervisor... CMMI ) - Acquisition (AQ) © 2011 The MITRE Corporation. All rights reserved 13 CMMI -Development Incremental iterative development (planning & execution...objectives Constructing games highlighting particular aspects of proposed CCOD® acquisition, and conducting exercises with Subject Matter Experts ( SMEs

76 FR 68044 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-54; Small Entity Compliance Guide

Science.gov (United States)

2011-11-02

... Acquisition Circular 2005-54; Small Entity Compliance Guide AGENCY: Department of Defense (DoD), General... Federal Acquisition Circular (FAC) 2005-54, which amend the Federal Acquisition Regulation (FAR... (FAR Case 2009-006) This final rule amends the FAR to implement Executive Order (E.O.) 13494, Economy...

75 FR 19179 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-41; Small Entity Compliance Guide

Science.gov (United States)

2010-04-13

... Acquisition Circular 2005-41; Small Entity Compliance Guide AGENCIES: Department of Defense (DoD), General... Federal Acquisition Circular (FAC) 2005-41 which amends the Federal Acquisition Regulation (FAR... projects where the total cost to the Government is $25 million or more in order to promote economy and...

Fate and lability of silver in soils: Effect of ageing

Science.gov (United States)

The fate and lability of added soluble Ag in soils over time was examined by measurement of labile metal (E-value) by isotopic dilution using the 110mAg radioactive isotope and the solid-phase speciation of Ag by X-ray absorption near edge structure (XANES) spectrosco...

Indexing mergers and acquisitions

OpenAIRE

Gang, Jianhua; Guo, Jie (Michael); Hu, Nan; Li, Xi

2017-01-01

We measure the efficiency of mergers and acquisitions by putting forward an index (the ‘M&A Index’) based on stochastic frontier analysis. The M&A Index is calculated for each takeover deal and is standardized between 0 and 1. An acquisition with a higher index encompasses higher efficiency. We find that takeover bids with higher M&A Indices are more likely to succeed. Moreover, the M&A Index shows a strong and positive relation with the acquirers’ post-acquisition stock perfo...

75 FR 14057 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-40; Introduction

Science.gov (United States)

2010-03-23

... the Civilian Agency Acquisition Council and the Defense Acquisition Regulations Council (Councils) in..., consider all the information in FAPIIS and PPIRS when making a responsibility determination, and notify the... appropriate for the official's consideration; and Enter a non-responsibility determination into FAPIIS. The...

75 FR 53127 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-45; Introduction

Science.gov (United States)

2010-08-30

... summarizes the Federal Acquisition Regulation (FAR) rules agreed to by the Civilian Agency Acquisition... Chambers. Cost or Pricing Data. III American Recovery 2009-008 Davis. and Reinvestment Act of 2009 (the Recovery Act)-- Buy American Requirements for Construction Materials. SUPPLEMENTARY INFORMATION: Summaries...

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...

Fate of accreting white dwarfs: Type I supernovae vs collapse

International Nuclear Information System (INIS)

Nomoto, Ken'ichi.

1986-01-01

The final fate of accreting C + O white dwarfs is either thermonuclear explosion or collapse, if the white dwarf mass grows to the Chandrasekhar mass. We discuss how the fate depends on the initial mass, age, composition of the white dwarf and the mass accretion rate. Relatively fast accretion leads to a carbon deflagration at low central density that gives rise to a Type Ia supernova. Slower accretion induces a helium detonation that could be observed as a Type Ib supernova. If the initial mass of the C + O white dwarf is larger than 1.2 Msub solar, a carbon deflagration starts at high central density and induces a collapse of the white dwarf to form a neutron star. We examine the critical condition for which a carbon deflagration leads to collapse, not explosion. For the case of explosion, we discuss to what extent the nucleosynthesis models are consistent with spectra of Type Ia and Ib supernovae. 61 refs., 18 figs

Hidden neural networks

DEFF Research Database (Denmark)

Krogh, Anders Stærmose; Riis, Søren Kamaric

1999-01-01

A general framework for hybrids of hidden Markov models (HMMs) and neural networks (NNs) called hidden neural networks (HNNs) is described. The article begins by reviewing standard HMMs and estimation by conditional maximum likelihood, which is used by the HNN. In the HNN, the usual HMM probability...... parameters are replaced by the outputs of state-specific neural networks. As opposed to many other hybrids, the HNN is normalized globally and therefore has a valid probabilistic interpretation. All parameters in the HNN are estimated simultaneously according to the discriminative conditional maximum...... likelihood criterion. The HNN can be viewed as an undirected probabilistic independence network (a graphical model), where the neural networks provide a compact representation of the clique functions. An evaluation of the HNN on the task of recognizing broad phoneme classes in the TIMIT database shows clear...

NeuroMEMS: Neural Probe Microtechnologies

Directory of Open Access Journals (Sweden)

Sam Musallam

2008-10-01

Full Text Available Neural probe technologies have already had a significant positive effect on our understanding of the brain by revealing the functioning of networks of biological neurons. Probes are implanted in different areas of the brain to record and/or stimulate specific sites in the brain. Neural probes are currently used in many clinical settings for diagnosis of brain diseases such as seizers, epilepsy, migraine, Alzheimer’s, and dementia. We find these devices assisting paralyzed patients by allowing them to operate computers or robots using their neural activity. In recent years, probe technologies were assisted by rapid advancements in microfabrication and microelectronic technologies and thus are enabling highly functional and robust neural probes which are opening new and exciting avenues in neural sciences and brain machine interfaces. With a wide variety of probes that have been designed, fabricated, and tested to date, this review aims to provide an overview of the advances and recent progress in the microfabrication techniques of neural probes. In addition, we aim to highlight the challenges faced in developing and implementing ultralong multi-site recording probes that are needed to monitor neural activity from deeper regions in the brain. Finally, we review techniques that can improve the biocompatibility of the neural probes to minimize the immune response and encourage neural growth around the electrodes for long term implantation studies.

Dual embryonic origin and patterning of the pharyngeal skeleton in the axolotl (Ambystoma mexicanum).

Science.gov (United States)

Sefton, Elizabeth M; Piekarski, Nadine; Hanken, James

2015-01-01

The impressive morphological diversification of vertebrates was achieved in part by innovation and modification of the pharyngeal skeleton. Extensive fate mapping in amniote models has revealed a primarily cranial neural crest derivation of the pharyngeal skeleton. Although comparable fate maps of amphibians produced over several decades have failed to document a neural crest derivation of ventromedial elements in these vertebrates, a recent report provides evidence of a mesodermal origin of one of these elements, basibranchial 2, in the axolotl. We used a transgenic labeling protocol and grafts of labeled cells between GFP+ and white embryos to derive a fate map that describes contributions of both cranial neural crest and mesoderm to the axolotl pharyngeal skeleton, and we conducted additional experiments that probe the mechanisms that underlie mesodermal patterning. Our fate map confirms a dual embryonic origin of the pharyngeal skeleton in urodeles, including derivation of basibranchial 2 from mesoderm closely associated with the second heart field. Additionally, heterotopic transplantation experiments reveal lineage restriction of mesodermal cells that contribute to pharyngeal cartilage. The mesoderm-derived component of the pharyngeal skeleton appears to be particularly sensitive to retinoic acid (RA): administration of exogenous RA leads to loss of the second basibranchial, but not the first. Neural crest was undoubtedly critical in the evolution of the vertebrate pharyngeal skeleton, but mesoderm may have played a central role in forming ventromedial elements, in particular. When and how many times during vertebrate phylogeny a mesodermal contribution to the pharyngeal skeleton evolved remain to be resolved. © 2015 Wiley Periodicals, Inc.

Developing Acquisition IS Integration Capabilities

DEFF Research Database (Denmark)

Wynne, Peter J.

2016-01-01

An under researched, yet critical challenge of Mergers and Acquisitions (M&A), is what to do with the two organisations’ information systems (IS) post-acquisition. Commonly referred to as acquisition IS integration, existing theory suggests that to integrate the information systems successfully......, an acquiring company must leverage two high level capabilities: diagnosis and integration execution. Through a case study, this paper identifies how a novice acquirer develops these capabilities in anticipation of an acquisition by examining its use of learning processes. The study finds the novice acquirer...... applies trial and error, experimental, and vicarious learning processes, while actively avoiding improvisational learning. The results of the study contribute to the acquisition IS integration literature specifically by exploring it from a new perspective: the learning processes used by novice acquirers...

Calo trigger acquisition system

CERN Multimedia

Franchini, Matteo

2016-01-01

Calo trigger acquisition system - Evolution of the acquisition system from a multiple boards system (upper, orange cables) to a single board one (below, light blue cables) where all the channels are collected in a single board.

The C. elegans Tailless/TLX transcription factor nhr-67 controls neuronal identity and left/right asymmetric fate diversification.

Science.gov (United States)

Sarin, Sumeet; Antonio, Celia; Tursun, Baris; Hobert, Oliver

2009-09-01

An understanding of the molecular mechanisms of cell fate determination in the nervous system requires the elucidation of transcriptional regulatory programs that ultimately control neuron-type-specific gene expression profiles. We show here that the C. elegans Tailless/TLX-type, orphan nuclear receptor NHR-67 acts at several distinct steps to determine the identity and subsequent left/right (L/R) asymmetric subtype diversification of a class of gustatory neurons, the ASE neurons. nhr-67 controls several broad aspects of sensory neuron development and, in addition, triggers the expression of a sensory neuron-type-specific selector gene, che-1, which encodes a zinc-finger transcription factor. Subsequent to its induction of overall ASE fate, nhr-67 diversifies the fate of the two ASE neurons ASEL and ASER across the L/R axis by promoting ASER and inhibiting ASEL fate. This function is achieved through direct expression activation by nhr-67 of the Nkx6-type homeobox gene cog-1, an inducer of ASER fate, that is inhibited in ASEL through the miRNA lsy-6. Besides controlling bilateral and asymmetric aspects of ASE development, nhr-67 is also required for many other neurons of diverse lineage history and function to appropriately differentiate, illustrating the broad and diverse use of this type of transcription factor in neuronal development.

Fukushima Daiichi-Derived Radionuclides in the Ocean: Transport, Fate, and Impacts.

Science.gov (United States)

Buesseler, Ken; Dai, Minhan; Aoyama, Michio; Benitez-Nelson, Claudia; Charmasson, Sabine; Higley, Kathryn; Maderich, Vladimir; Masqué, Pere; Morris, Paul J; Oughton, Deborah; Smith, John N

2017-01-03

The events that followed the Tohoku earthquake and tsunami on March 11, 2011, included the loss of power and overheating at the Fukushima Daiichi nuclear power plants, which led to extensive releases of radioactive gases, volatiles, and liquids, particularly to the coastal ocean. The fate of these radionuclides depends in large part on their oceanic geochemistry, physical processes, and biological uptake. Whereas radioactivity on land can be resampled and its distribution mapped, releases to the marine environment are harder to characterize owing to variability in ocean currents and the general challenges of sampling at sea. Five years later, it is appropriate to review what happened in terms of the sources, transport, and fate of these radionuclides in the ocean. In addition to the oceanic behavior of these contaminants, this review considers the potential health effects and societal impacts.

Releasing characteristics and fate of heavy metals from phytoremediation crop residues during anaerobic digestion.

Science.gov (United States)

Lee, Jongkeun; Park, Ki Young; Cho, Jinwoo; Kim, Jae Young

2018-01-01

In this study, lab-scale batch tests were conducted to investigate releasing characteristics of heavy metals according to degradation of heavy metal containing biomass. The fate of heavy metals after released from biomass was also determined through adsorption tests and Visual MINTEQ simulation. According to the anaerobic batch test results as well as volatile solids and carbon balance analyses, maximum of 60% by wt. of biomass was degraded. During the anaerobic biodegradation, among Cd, Cu, Ni, Pb, and Zn, only Cu and Zn were observed in soluble form (approximately 40% by wt. of input mass). The discrepancy between degradation ratio of biomass and ratio of released heavy metals mass from biomass was observed. It seems that this discordance was caused by the fate (i.e., precipitated with sulfur/hydroxide or adsorbed onto sorbents) of each heavy metal types in solution after being released from biomass. Thus, releasing characteristics and fate of heavy metal should be considered carefully to predict stability of anaerobic digestion process for heavy metal-containing biomass. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fate and Transport of Shale-derived, Biogenic Methane.

Science.gov (United States)

Hendry, M Jim; Schmeling, Erin E; Barbour, S Lee; Huang, M; Mundle, Scott O C

2017-07-07

Natural gas extraction from unconventional shale gas reservoirs is the subject of considerable public debate, with a key concern being the impact of leaking fugitive natural gases on shallow potable groundwater resources. Baseline data regarding the distribution, fate, and transport of these gases and their isotopes through natural formations prior to development are lacking. Here, we define the migration and fate of CH 4 and δ 13 C-CH 4 from an early-generation bacterial gas play in the Cretaceous of the Williston Basin, Canada to the water table. Our results show the CH 4 is generated at depth and diffuses as a conservative species through the overlying shale. We also show that the diffusive fractionation of δ 13 C-CH 4 (following glaciation) can complicate fugitive gas interpretations. The sensitivity of the δ 13 C-CH 4 profile to glacial timing suggests it may be a valuable tracer for characterizing the timing of geologic changes that control transport of CH 4 (and other solutes) and distinguishing between CH 4 that rapidly migrates upward through a well annulus or other conduit and CH 4 that diffuses upwards naturally. Results of this study were used to provide recommendations for designing baseline investigations.

Fate of a mutation in a fluctuating environment

Science.gov (United States)

Cvijović, Ivana; Good, Benjamin H.; Jerison, Elizabeth R.; Desai, Michael M.

2015-01-01

Natural environments are never truly constant, but the evolutionary implications of temporally varying selection pressures remain poorly understood. Here we investigate how the fate of a new mutation in a fluctuating environment depends on the dynamics of environmental variation and on the selective pressures in each condition. We find that even when a mutation experiences many environmental epochs before fixing or going extinct, its fate is not necessarily determined by its time-averaged selective effect. Instead, environmental variability reduces the efficiency of selection across a broad parameter regime, rendering selection unable to distinguish between mutations that are substantially beneficial and substantially deleterious on average. Temporal fluctuations can also dramatically increase fixation probabilities, often making the details of these fluctuations more important than the average selection pressures acting on each new mutation. For example, mutations that result in a trade-off between conditions but are strongly deleterious on average can nevertheless be more likely to fix than mutations that are always neutral or beneficial. These effects can have important implications for patterns of molecular evolution in variable environments, and they suggest that it may often be difficult for populations to maintain specialist traits, even when their loss leads to a decline in time-averaged fitness. PMID:26305937

A Robust Single Primate Neuroepithelial Cell Clonal Expansion System for Neural Tube Development and Disease Studies

Directory of Open Access Journals (Sweden)

Xiaoqing Zhu

2016-02-01

Full Text Available Developing a model of primate neural tube (NT development is important to promote many NT disorder studies in model organisms. Here, we report a robust and stable system to allow for clonal expansion of single monkey neuroepithelial stem cells (NESCs to develop into miniature NT-like structures. Single NESCs can produce functional neurons in vitro, survive, and extensively regenerate neuron axons in monkey brain. NT formation and NESC maintenance depend on high metabolism activity and Wnt signaling. NESCs are regionally restricted to a telencephalic fate. Moreover, single NESCs can turn into radial glial progenitors (RGPCs. The transition is accurately regulated by Wnt signaling through regulation of Notch signaling and adhesion molecules. Finally, using the “NESC-TO-NTs” system, we model the functions of folic acid (FA on NT closure and demonstrate that FA can regulate multiple mechanisms to prevent NT defects. Our system is ideal for studying NT development and diseases.

Magical thinking in predictions of negative events: Evidence for tempting fate but not for a protection effect

Directory of Open Access Journals (Sweden)