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Sample records for spontaneous miniature ipscs

  1. Spontaneous Vesicle Fusion Is Differentially Regulated at Cholinergic and GABAergic Synapses

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    Haowen Liu

    2018-02-01

    Full Text Available The locomotion of C. elegans is balanced by excitatory and inhibitory neurotransmitter release at neuromuscular junctions. However, the molecular mechanisms that maintain the balance of synaptic transmission remain enigmatic. Here, we investigated the function of voltage-gated Ca2+ channels in triggering spontaneous release at cholinergic and GABAergic synapses. Recordings of the miniature excitatory/inhibitory postsynaptic currents (mEPSCs and mIPSCs, respectively showed that UNC-2/CaV2 and EGL-19/CaV1 channels are the two major triggers for spontaneous release. Notably, however, Ca2+-independent spontaneous release was observed at GABAergic but not cholinergic synapses. Functional screening led to the identification of hypomorphic unc-64/Syntaxin-1A and snb-1/VAMP2 mutants in which mEPSCs are severely impaired, whereas mIPSCs remain unaltered, indicating differential regulation of these currents at cholinergic and GABAergic synapses. Moreover, Ca2+-independent spontaneous GABA release was nearly abolished in the hypomorphic unc-64 and snb-1 mutants, suggesting distinct mechanisms for Ca2+-dependent and Ca2+-independent spontaneous release.

  2. Nitric oxide-related species inhibit evoked neurotransmission but enhance spontaneous miniature synaptic currents in central neuronal cultures

    OpenAIRE

    Pan, Zhuo-Hua; Segal, Michael M.; Lipton, Stuart A.

    1996-01-01

    Nitric oxide (NO·) does not react significantly with thiol groups under physiological conditions, whereas a variety of endogenous NO donor molecules facilitate rapid transfer to thiol of nitrosonium ion (NO+, with one less electron than NO·). Here, nitrosonium donors are shown to decrease the efficacy of evoked neurotransmission while increasing the frequency of spontaneous miniature excitatory postsynaptic currents (mEPSCs). In contrast, pure NO· donors have littl...

  3. Effects of met-enkephalin on GABAergic spontaneous miniature IPSPs in organotypic slice cultures of the rat hippocampus

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    Rekling, J C

    1993-01-01

    The action of met-enkephalin on GABAergic spontaneous miniature IPSPs (smIPSPs) was investigated in CA1 neurons from hippocampal slice cultures. In the presence of excitatory amino acid blockers (2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline, DL-2-amino-5-phosphonovaleric acid) and TTX...... the amplitude distribution of the smIPSPs. The proportion of "large" smIPSPs was reduced, but a loss of "small" smIPSPs also contributed to the reduction in smIPSP frequency. The selective mu-receptor agonist DAGO mimicked the effect of met-enkephalin and naloxone blocked the effect of DAGO. Hyperpolarization......IPSP frequency, nor did it block the effect of DAGO. These results suggest that CA1 pyramidal cells of hippocampal organotypic cultures are tonically inhibited by spontaneous release of GABA, through a release mechanism that is independent of propagated sodium action potentials. Met-enkephalin and DAGO reduce...

  4. Establishment of induced pluripotent stem cell (iPSC line from a 75-year old patient with late onset Alzheimer's disease (LOAD

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    Zsuzsanna Táncos

    2016-07-01

    Full Text Available Peripheral blood mononuclear cells (PBMCs were collected from a clinically characterised 75-year old woman with late onset Alzheimer's disease (LOAD. The PMBCs were reprogrammed with the human OSKM transcription factors using the Sendai-virus delivery system. The transgene-free iPSC showed pluripotency verified by immunocytochemistry for pluripotency markers and differentiated spontaneously towards the 3 germ layers in vitro. Furthermore, the iPSC line showed normal karyotype. Our model might offer a good platform to further study the pathomechanism of sporadic AD, to identify early biomarkers and also for drug testing and gene therapy studies.

  5. Effects of Ketamine on Neuronal Spontaneous Excitatory Postsynaptic Currents and Miniature Excitatory Postsynaptic Currents in the Somatosensory Cortex of Rats

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    Chengdong Yuan

    2016-07-01

    Full Text Available Background: Ketamine is a commonly used intravenous anesthetic which produces dissociation anesthesia, analgesia, and amnesia. The mechanism of ketamine-induced synaptic inhibition in high-level cortical areas is still unknown. We aimed to elucidate the effects of different concentrations of ketamine on the glutamatergic synaptic transmission of the neurons in the primary somatosensory cortex by using the whole-cell patch-clamp method. Methods: Sprague-Dawley rats (11–19 postnatal days, n=36 were used to obtain brain slices (300 μM. Spontaneous excitatory postsynaptic currents (data from 40 neurons were recorded at a command potential of -70 mV in the presence of bicuculline (a competitive antagonist of GABAA receptors, 30 μM and strychnine (glycine receptor antagonist, 30 μM. Miniature excitatory postsynaptic currents (data from 40 neurons were also recorded when 1 μM of tetrodotoxin was added into the artificial cerebrospinal fluid. We used GraphPad Prism5for statistical analysis. Significant differences in the mean amplitude and frequency were tested using the Student paired 2-tailed t test. Values of P<0.05 were considered significant. Results: Different concentrations of ketamine inhibited the frequency and amplitude of the spontaneous excitatory postsynaptic currents as well as the amplitude of the miniature excitatory postsynaptic currents in a concentration-dependent manner, but they exerted no significant effect on the frequency of the miniature excitatory postsynaptic currents. Conclusion: Ketamine inhibited the excitatory synaptic transmission of the neurons in the primary somatosensory cortex. The inhibition may have been mediated by a reduction in the sensitivity of the postsynaptic glutamatergic receptors.

  6. iPSC Core

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    Federal Laboratory Consortium — The induced Pluripotent Stem Cells (iPSC) Core was created in 2011 to accelerate stem cell research in the NHLBI by providing investigators consultation, technical...

  7. Whisker Deprivation Drives Two Phases of Inhibitory Synapse Weakening in Layer 4 of Rat Somatosensory Cortex.

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    Melanie A Gainey

    Full Text Available Inhibitory synapse development in sensory neocortex is experience-dependent, with sustained sensory deprivation yielding fewer and weaker inhibitory synapses. Whether this represents arrest of synapse maturation, or a more complex set of processes, is unclear. To test this, we measured the dynamics of inhibitory synapse development in layer 4 of rat somatosensory cortex (S1 during continuous whisker deprivation from postnatal day 7, and in age-matched controls. In deprived columns, spontaneous miniature inhibitory postsynaptic currents (mIPSCs and evoked IPSCs developed normally until P15, when IPSC amplitude transiently decreased, recovering by P16 despite ongoing deprivation. IPSCs remained normal until P22, when a second, sustained phase of weakening began. Delaying deprivation onset by 5 days prevented the P15 weakening. Both early and late phase weakening involved measurable reduction in IPSC amplitude relative to prior time points. Thus, deprivation appears to drive two distinct phases of active IPSC weakening, rather than simple arrest of synapse maturation.

  8. The Relevance of AgRP Neuron-Derived GABA Inputs to POMC Neurons Differs for Spontaneous and Evoked Release

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    Rau, Andrew R.; Hentges, Shane T.

    2017-01-01

    Hypothalamic agouti-related peptide (AgRP) neurons potently stimulate food intake, whereas proopiomelanocortin (POMC) neurons inhibit feeding. Whether AgRP neurons exert their orexigenic actions, at least in part, by inhibiting anorexigenic POMC neurons remains unclear. Here, the connectivity between GABA-releasing AgRP neurons and POMC neurons was examined in brain slices from male and female mice. GABA-mediated spontaneous IPSCs (sIPSCs) in POMC neurons were unaffected by disturbing GABA re...

  9. Engineering-derived approaches for iPSC preparation, expansion, differentiation and applications.

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    Li, Yang; Li, Ling; Chen, Zhi-Nan; Gao, Ge; Yao, Rui; Sun, Wei

    2017-07-31

    Remarkable achievements have been made since induced pluripotent stem cells (iPSCs) were first introduced in 2006. Compared with non-pluripotent stem cells, iPSC research faces several additional complexities, such as the choice of extracellular matrix proteins, growth and differentiation factors, as well as technical challenges related to self-renewal and directed differentiation. Overcoming these challenges requires the integration of knowledge and technologies from multiple fields including cell biology, biomaterial science, engineering, physics and medicine. Here, engineering-derived iPSC approaches are reviewed according to three aspects of iPSC studies: preparation, expansion, differentiation and applications. Engineering strategies, such as 3D systems establishment, cell-matrix mechanics and the regulation of biophysical and biochemical cues, together with engineering techniques, such as 3D scaffolds, cell microspheres and bioreactors, have been applied to iPSC studies and have generated insightful results and even mini-organs such as retinas, livers and intestines. Specific results are given to demonstrate how these approaches impact iPSC behavior, and related mechanisms are discussed. In addition, cell printing technologies are presented as an advanced engineering-derived approach since they have been applied in both iPSC studies and the construction of diverse tissues and organs. Further development and possible innovations of cell printing technologies are presented in terms of creating complex and functional iPSC-derived living tissues and organs.

  10. The State of Play with iPSCs and Spinal Cord Injury Models

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    Stuart I. Hodgetts

    2015-01-01

    Full Text Available The application of induced pluripotent stem cell (iPSC technologies in cell based strategies, for the repair of the central nervous system (with particular focus on the spinal cord, is moving towards the potential use of clinical grade donor cells. The ability of iPSCs to generate donor neuronal, glial and astrocytic phenotypes for transplantation is highlighted here, and we review recent research using iPSCs in attempts to treat spinal cord injury in various animal models. Also discussed are issues relating to the production of clinical grade iPSCs, recent advances in transdifferentiation protocols for iPSC-derived donor cell populations, concerns about tumourogenicity, and whether iPSC technologies offer any advantages over previous donor cell candidates or tissues already in use as therapeutic tools in experimental spinal cord injury studies.

  11. Innervation by a GABAergic neuron depresses spontaneous release in glutamatergic neurons and unveils the clamping phenotype of synaptotagmin-1

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    Wierda, Keimpe D B; Sørensen, Jakob Balslev

    2014-01-01

    The role of spontaneously occurring release events in glutamatergic and GABAergic neurons and their regulation is intensely debated. To study the interdependence of glutamatergic and GABAergic spontaneous release, we compared reciprocally connected "mixed" glutamatergic/GABAergic neuronal pairs...... from mice cultured on astrocyte islands with "homotypic" glutamatergic or GABAergic pairs and autaptic neurons. We measured mEPSC and mIPSC frequencies simultaneously from both neurons. Neuronal pairs formed both interneuronal synaptic and autaptic connections indiscriminately. We find that whereas m......EPSC and mIPSC frequencies did not deviate between autaptic and synaptic connections, the frequency of mEPSCs in mixed pairs was strongly depressed compared with either autaptic neurons or glutamatergic pairs. Simultaneous imaging of synapses, or comparison to evoked release amplitudes, showed...

  12. Sirt6 Promotes DNA End Joining in iPSCs Derived from Old Mice

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    Wen Chen

    2017-03-01

    Full Text Available Induced pluripotent stem cells (iPSCs have great potential for treating age-related diseases, but the genome integrity of iPSCs is critically important. Here, we demonstrate that non-homologous end joining (NHEJ, rather than homologous recombination (HR, is less efficient in iPSCs from old mice than young mice. We further find that Sirt6 is downregulated in iPSCs from old mice. Sirt6 directly binds to Ku80 and facilitates the Ku80/DNA-PKcs interaction, thus promoting DNA-PKcs phosphorylation at residue S2056, leading to efficient NHEJ. Rescue experiments show that introducing a combination of Sirt6 and the Yamanaka factors during reprogramming significantly promotes DNA double-strand break (DSB repair by activating NHEJ in iPSCs derived from old mice. Thus, our study suggests a strategy to improve the quality of iPSCs derived from old donors by activating NHEJ and stabilizing the genome.

  13. The Relevance of AgRP Neuron-Derived GABA Inputs to POMC Neurons Differs for Spontaneous and Evoked Release.

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    Rau, Andrew R; Hentges, Shane T

    2017-08-02

    Hypothalamic agouti-related peptide (AgRP) neurons potently stimulate food intake, whereas proopiomelanocortin (POMC) neurons inhibit feeding. Whether AgRP neurons exert their orexigenic actions, at least in part, by inhibiting anorexigenic POMC neurons remains unclear. Here, the connectivity between GABA-releasing AgRP neurons and POMC neurons was examined in brain slices from male and female mice. GABA-mediated spontaneous IPSCs (sIPSCs) in POMC neurons were unaffected by disturbing GABA release from AgRP neurons either by cell type-specific deletion of the vesicular GABA transporter or by expression of botulinum toxin in AgRP neurons to prevent vesicle-associated membrane protein 2-dependent vesicle fusion. Additionally, there was no difference in the ability of μ-opioid receptor (MOR) agonists to inhibit sIPSCs in POMC neurons when MORs were deleted from AgRP neurons, and activation of the inhibitory designer receptor hM4Di on AgRP neurons did not affect sIPSCs recorded from POMC neurons. These approaches collectively indicate that AgRP neurons do not significantly contribute to the strong spontaneous GABA input to POMC neurons. Despite these observations, optogenetic stimulation of AgRP neurons reliably produced evoked IPSCs in POMC neurons, leading to the inhibition of POMC neuron firing. Thus, AgRP neurons can potently affect POMC neuron function without contributing a significant source of spontaneous GABA input to POMC neurons. Together, these results indicate that the relevance of GABAergic inputs from AgRP to POMC neurons is state dependent and highlight the need to consider different types of transmitter release in circuit mapping and physiologic regulation. SIGNIFICANCE STATEMENT Agouti-related peptide (AgRP) neurons play an important role in driving food intake, while proopiomelanocortin (POMC) neurons inhibit feeding. Despite the importance of these two well characterized neuron types in maintaining metabolic homeostasis, communication between these

  14. Antiarrhythmic Effects of Dantrolene in Patients with Catecholaminergic Polymorphic Ventricular Tachycardia and Replication of the Responses Using iPSC Models.

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    Kirsi Penttinen

    Full Text Available Catecholaminergic polymorphic ventricular tachycardia (CPVT is a highly malignant inherited arrhythmogenic disorder. Type 1 CPVT (CPVT1 is caused by cardiac ryanodine receptor (RyR2 gene mutations resulting in abnormal calcium release from sarcoplasmic reticulum. Dantrolene, an inhibitor of sarcoplasmic Ca(2+ release, has been shown to rescue this abnormal Ca(2+ release in vitro. We assessed the antiarrhythmic efficacy of dantrolene in six patients carrying various RyR2 mutations causing CPVT. The patients underwent exercise stress test before and after dantrolene infusion. Dantrolene reduced the number of premature ventricular complexes (PVCs on average by 74% (range 33-97 in four patients with N-terminal or central mutations in the cytosolic region of the RyR2 protein, while dantrolene had no effect in two patients with mutations in or near the transmembrane domain. Induced pluripotent stem cells (iPSCs were generated from all the patients and differentiated into spontaneously beating cardiomyocytes (CMs. The antiarrhythmic effect of dantrolene was studied in CMs after adrenaline stimulation by Ca(2+ imaging. In iPSC derived CMs with RyR2 mutations in the N-terminal or central region, dantrolene suppressed the Ca(2+ cycling abnormalities in 80% (range 65-97 of cells while with mutations in or near the transmembrane domain only in 23 or 32% of cells. In conclusion, we demonstrate that dantrolene given intravenously shows antiarrhythmic effects in a portion of CPVT1 patients and that iPSC derived CM models replicate these individual drug responses. These findings illustrate the potential of iPSC models to individualize drug therapy of inherited diseases.Trial Registration: EudraCT Clinical Trial Registry 2012-005292-14.

  15. Presynaptic CRF1 Receptors Mediate the Ethanol Enhancement of GABAergic Transmission in the Mouse Central Amygdala

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    Zhiguo Nie

    2009-01-01

    Full Text Available Corticotropin-releasing factor (CRF is a 41-amino-acid neuropeptide involved in stress responses initiated from several brain areas, including the amygdala formation. Research shows a strong relationship between stress, brain CRF, and excessive alcohol consumption. Behavioral studies suggest that the central amygdala (CeA is significantly involved in alcohol reward and dependence. We recently reported that the ethanol augmentation of GABAergic synaptic transmission in rat CeA involves CRF1 receptors, because both CRF and ethanol significantly enhanced the amplitude of evoked GABAergic inhibitory postsynaptic currents (IPSCs in CeA neurons from wild-type (WT and CRF2 knockout (KO mice, but not in neurons of CRF1 KO mice. The present study extends these findings using selective CRF receptor ligands, gene KO models, and miniature IPSC (mIPSC analysis to assess further a presynaptic role for the CRF receptors in mediating ethanol effects in the CeA. In whole-cell patch recordings of pharmacologically isolated GABAAergic IPSCs from slices of mouse CeA, both CRF and ethanol augmented evoked IPSCs in a concentration-dependent manner, with low EC50s. A CRF1 (but not CRF2 KO construct and the CRF1-selective nonpeptide antagonist NIH-3 (LWH-63 blocked the augmenting effect of both CRF and ethanol on evoked IPSCs. Furthermore, the new selective CRF1 agonist stressin1, but not the CRF2 agonist urocortin 3, also increased evoked IPSC amplitudes. Both CRF and ethanol decreased paired-pulse facilitation (PPF of evoked IPSCs and significantly enhanced the frequency, but not the amplitude, of spontaneous miniature GABAergic mIPSCs in CeA neurons of WT mice, suggesting a presynaptic site of action. The PPF effect of ethanol was abolished in CeA neurons of CRF1 KO mice. The CRF1 antagonist NIH-3 blocked the CRF- and ethanol-induced enhancement of mIPSC frequency in CeA neurons. These data indicate that presynaptic CRF1 receptors play a critical role in permitting

  16. Translation of Human iPSCs: From Clinical Trial in a Dish to Precision Medicine

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    Sayed, Nazish; Liu, Chun; Wu, Joseph C.

    2016-01-01

    The prospect of changing the plasticity of terminally differentiated cells toward pluripotency has completely altered the outlook of biomedical research. Human induced pluripotent stem cells (iPSCs) provide a new source of therapeutic cells free from the ethical issues or immune barriers of human embryonic stem cells. iPSCs also confer considerable advantages over conventional methods of studying human diseases. Since its advent, iPSC technology has expanded, with 3 major applications: disease modeling; regenerative therapy; and drug discovery. Here we discuss, in a comprehensive manner, the recent advances in iPSC technology in relation to basic, clinical, and population health. PMID:27151349

  17. Hypocretin (orexin) regulates glutamate input to fast-spiking interneurons in layer V of the Fr2 region of the murine prefrontal cortex.

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    Aracri, Patrizia; Banfi, Daniele; Pasini, Maria Enrica; Amadeo, Alida; Becchetti, Andrea

    2015-05-01

    We studied the effect of hypocretin 1 (orexin A) in the frontal area 2 (Fr2) of the murine neocortex, implicated in the motivation-dependent goal-directed tasks. In layer V, hypocretin stimulated the spontaneous excitatory postsynaptic currents (EPSCs) on fast-spiking (FS) interneurons. The effect was accompanied by increased frequency of miniature EPSCs, indicating that hypocretin can target the glutamatergic terminals. Moreover, hypocretin stimulated the spontaneous inhibitory postsynaptic currents (IPSCs) on pyramidal neurons, with no effect on miniature IPSCs. This action was prevented by blocking 1) the ionotropic glutamatergic receptors; 2) the hypocretin receptor type 1 (HCRTR-1), with SB-334867. Finally, hypocretin increased the firing frequency in FS cells, and the effect was blocked when the ionotropic glutamate transmission was inhibited. Immunolocalization confirmed that HCRTR-1 is highly expressed in Fr2, particularly in layer V-VI. Conspicuous labeling was observed in pyramidal neuron somata and in VGLUT1+ glutamatergic terminals, but not in VGLUT2+ fibers (mainly thalamocortical afferents). The expression of HCRTR-1 in GABAergic structures was scarce. We conclude that 1) hypocretin regulates glutamate release in Fr2; 2) the effect presents a presynaptic component; 3) the peptide control of FS cells is indirect, and probably mediated by the regulation of glutamatergic input onto these cells. © The Author 2013. Published by Oxford University Press.

  18. The Epigenetic Reprogramming Roadmap in Generation of iPSCs from Somatic Cells

    DEFF Research Database (Denmark)

    Brix, Jacob; Zhou, Yan; Luo, Yonglun

    2015-01-01

    Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) is a comprehensive epigenetic process involving genome-wide modifications of histones and DNA methylation. This process is often incomplete, which subsequently affects iPSC reprograming, pluripotency, and differentiation cap...

  19. Heme oxygenase-1 affects generation and spontaneous cardiac differentiation of induced pluripotent stem cells.

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    Stepniewski, Jacek; Pacholczak, Tomasz; Skrzypczyk, Aniela; Ciesla, Maciej; Szade, Agata; Szade, Krzysztof; Bidanel, Romain; Langrzyk, Agnieszka; Grochowski, Radoslaw; Vandermeeren, Felix; Kachamakova-Trojanowska, Neli; Jez, Mateusz; Drabik, Grazyna; Nakanishi, Mahito; Jozkowicz, Alicja; Dulak, Jozef

    2018-02-01

    Cellular stress can influence efficiency of iPSCs generation and their differentiation. However, the role of intracellular cytoprotective factors in these processes is still not well known. Therefore, we investigated the effect of HO-1 (Hmox1) or Nrf2 (Nfe2l2), two major cytoprotective genes. Hmox1 -/- fibroblasts demonstrated decreased reprogramming efficiency in comparison to Hmox1 +/+ cells. Reversely, pharmacological enhancement of HO-1 resulted in higher number of iPSCs colonies. Importantly, elevated level of both p53 and p53-regulated miR-34a and 14-3-3σ was observed in HO-1-deficient fibroblasts whereas downregulation of p53 in these cells markedly increased their reprogramming efficiency. In human fibroblasts HO-1 silencing also induced p53 expression and affected reprogramming outcome. Hmox1 +/+ and Hmox1 -/- iPSCs similarly differentiated in vitro to cells originating from three germ layers, however, lower number of contracting cells was observed during this process in HO-1-deficient cells indicating attenuated cardiac differentiation. Importantly, silencing of Hmox1 in murine ESC using CRISPR/Cas-9 editing also impaired their spontaneous cardiac differentiation. Decreased reprogramming efficiency was also observed in Nrf2-lacking fibroblasts. Reversely, sulforaphane, a Nrf2 activator, increased the number of iPSCs colonies. However, both Nfe2l2 +/+ and Nfe2l2 -/- iPSCs showed similar pluripotency and differentiation capacity. These results indicate that regulation of HO-1 expression can further optimize generation and cardiac differentiation of iPSCs. © 2018 IUBMB Life, 70(2):129-142, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

  20. Stationary and non-stationary occurrences of miniature end plate potentials are well described as stationary and non-stationary Poisson processes in the mollusc Navanax inermis.

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    Cappell, M S; Spray, D C; Bennett, M V

    1988-06-28

    Protractor muscles in the gastropod mollusc Navanax inermis exhibit typical spontaneous miniature end plate potentials with mean amplitude 1.71 +/- 1.19 (standard deviation) mV. The evoked end plate potential is quantized, with a quantum equal to the miniature end plate potential amplitude. When their rate is stationary, occurrence of miniature end plate potentials is a random, Poisson process. When non-stationary, spontaneous miniature end plate potential occurrence is a non-stationary Poisson process, a Poisson process with the mean frequency changing with time. This extends the random Poisson model for miniature end plate potentials to the frequently observed non-stationary occurrence. Reported deviations from a Poisson process can sometimes be accounted for by the non-stationary Poisson process and more complex models, such as clustered release, are not always needed.

  1. Human iPSC for Therapeutic Approaches to the Nervous System: Present and Future Applications

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    Maria Giuseppina Cefalo

    2016-01-01

    Full Text Available Many central nervous system (CNS diseases including stroke, spinal cord injury (SCI, and brain tumors are a significant cause of worldwide morbidity/mortality and yet do not have satisfying treatments. Cell-based therapy to restore lost function or to carry new therapeutic genes is a promising new therapeutic approach, particularly after human iPSCs became available. However, efficient generation of footprint-free and xeno-free human iPSC is a prerequisite for their clinical use. In this paper, we will first summarize the current methodology to obtain footprint- and xeno-free human iPSC. We will then review the current iPSC applications in therapeutic approaches for CNS regeneration and their use as vectors to carry proapoptotic genes for brain tumors and review their applications for modelling of neurological diseases and formulating new therapeutic approaches. Available results will be summarized and compared. Finally, we will discuss current limitations precluding iPSC from being used on large scale for clinical applications and provide an overview of future areas of improvement. In conclusion, significant progress has occurred in deriving iPSC suitable for clinical use in the field of neurological diseases. Current efforts to overcome technical challenges, including reducing labour and cost, will hopefully expedite the integration of this technology in the clinical setting.

  2. Generation of iPSC lines from primary human chorionic villi cells

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    Björn Lichtner

    2015-11-01

    Full Text Available Primary human chorionic villi (CV cells were used to generate the iPSC line by retroviral transduction of the four Yamanaka-factors OCT4, SOX2, KLF4 and c-MYC. Pluripotency was confirmed both in vivo and in vitro. The transcriptomes of the CV-derived iPSC lines and the human embryonic stem cell lines—H1 and H9 have a Pearson correlation of 0.929 and 0.943 respectively.

  3. Reprogramming LCLs to iPSCs Results in Recovery of Donor-Specific Gene Expression Signature.

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    Samantha M Thomas

    2015-05-01

    Full Text Available Renewable in vitro cell cultures, such as lymphoblastoid cell lines (LCLs, have facilitated studies that contributed to our understanding of genetic influence on human traits. However, the degree to which cell lines faithfully maintain differences in donor-specific phenotypes is still debated. We have previously reported that standard cell line maintenance practice results in a loss of donor-specific gene expression signatures in LCLs. An alternative to the LCL model is the induced pluripotent stem cell (iPSC system, which carries the potential to model tissue-specific physiology through the use of differentiation protocols. Still, existing LCL banks represent an important source of starting material for iPSC generation, and it is possible that the disruptions in gene regulation associated with long-term LCL maintenance could persist through the reprogramming process. To address this concern, we studied the effect of reprogramming mature LCL cultures from six unrelated donors to iPSCs on the ensuing gene expression patterns within and between individuals. We show that the reprogramming process results in a recovery of donor-specific gene regulatory signatures, increasing the number of genes with a detectable donor effect by an order of magnitude. The proportion of variation in gene expression statistically attributed to donor increases from 6.9% in LCLs to 24.5% in iPSCs (P < 10-15. Since environmental contributions are unlikely to be a source of individual variation in our system of highly passaged cultured cell lines, our observations suggest that the effect of genotype on gene regulation is more pronounced in iPSCs than in LCLs. Our findings indicate that iPSCs can be a powerful model system for studies of phenotypic variation across individuals in general, and the genetic association with variation in gene regulation in particular. We further conclude that LCLs are an appropriate starting material for iPSC generation.

  4. From iPSC towards cardiac tissue-a road under construction.

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    Peischard, Stefan; Piccini, Ilaria; Strutz-Seebohm, Nathalie; Greber, Boris; Seebohm, Guiscard

    2017-10-01

    The possibility to generate induced pluripotent stem cells (iPSC) opens the way to generate virtually all cell types of our human body. In combination with modern gene editing techniques like CRISPR/CAS, a new set of powerful tools becomes available for life science. Scientific fields like genotype and cell type-specific pharmacology, disease modeling, stem cell biology, and developmental biology have been dramatically fostered and their faces have been changed. However, as golden as the age of iPSC-derived cells and their manipulation has started, the shine begins to tarnish. Researchers face more and more practical problems intrinsic to the system. These problems are related to the specific culturing conditions which are not yet sufficient to mimic the natural environment of native stem cells differentiating towards adult cells. However, researchers work hard to uncover these factors. Here, we review a common standard approach to generate iPSCs and transduce these to iPSC cardiomyocytes. Further, we review recent achievements and discuss their current limitations and future perspectives. We are on track, but the road is still under construction.

  5. Extracellular pH modulates GABAergic neurotransmission in rat hypothalamus.

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    Chen, Z L; Huang, R Q

    2014-06-20

    Changes in extracellular pH have a modulatory effect on GABAA receptor function. It has been reported that pH sensitivity of the GABA receptor is dependent on subunit composition and GABA concentration. Most of previous investigations focused on GABA-evoked currents, which only reflect the postsynaptic receptors. The physiological relevance of pH modulation of GABAergic neurotransmission is not fully elucidated. In the present studies, we examined the influence of extracellular pH on the GABAA receptor-mediated inhibitory neurotransmission in rat hypothalamic neurons. The inhibitory postsynaptic currents (IPSCs), tonic currents, and the GABA-evoked currents were recorded with whole-cell patch techniques on the hypothalamic slices from Sprague-Dawley rats at 15-26 postnatal days. The amplitude and frequency of spontaneous GABA IPSCs were significantly increased while the external pH was changed from 7.3 to 8.4. In the acidic pH (6.4), the spontaneous GABA IPSCs were reduced in amplitude and frequency. The pH induced changes in miniature GABA IPSCs (mIPSCs) similar to that in spontaneous IPSCs. The pH effect on the postsynaptic GABA receptors was assessed with exogenously applied varying concentrations of GABA. The tonic currents and the currents evoked by sub-saturating concentration of GABA ([GABA]) (10 μM) were inhibited by acidic pH and potentiated by alkaline pH. In contrast, the currents evoked by saturating [GABA] (1mM) were not affected by pH changes. We also investigated the influence of pH buffers and buffering capacity on pH sensitivity of GABAA receptors on human recombinant α1β2γ2 GABAA receptors stably expressed in HEK 293 cells. The pH influence on GABAA receptors was similar in HEPES- and MES-buffered media, and not dependent on protonated buffers, suggesting that the observed pH effect on GABA response is a specific consequence of changes in extracellular protons. Our data suggest that the hydrogen ions suppress the GABAergic neurotransmission

  6. Inhibition of GABAergic Neurotransmission by HIV-1 Tat and Opioid Treatment in the Striatum Involves μ-opioid Receptors

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    Changqing Xu

    2016-11-01

    Full Text Available Due to combined antiretroviral therapy (cART, human immunodeficiency virus type 1 (HIV-1 is considered a chronic disease with high prevalence of mild forms of neurocognitive impairments, also referred to as HIV-associated neurocognitive disorders (HAND. Although opiate drug use can exacerbate HIV-1 Tat-induced neuronal damage, it remains unknown how and to what extent opioids interact with Tat on the GABAergic system. We conducted whole-cell recordings in mouse striatal slices and examined the effects of HIV-1 Tat in the presence and absence of morphine (1 μM and damgo (1 μM on GABAergic neurotransmission. Results indicated a decrease in the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs and miniature IPSCs (mIPSCs by Tat (5 – 50 nM in a concentration-dependent manner. The significant Tat-induced decrease in IPSCs was abolished when removing extracellular and/or intracellular calcium. Treatment with morphine or damgo alone significantly decreased the frequency, but not amplitude of IPSCs. Interestingly, morphine but not damgo indicated an additional downregulation of the mean frequency of mIPSCs in combination with Tat. Pretreatment with naloxone (1 μM and CTAP (1 μM prevented the Tat-induced decrease in sIPSCs frequency but only naloxone prevented the combined Tat and morphine effect on mIPSCs frequency. Results indicate a Tat- or opioid-induced decrease in GABAergic neurotransmission via µ-opioid receptors with combined Tat and morphine effects involving additional opioid receptor-related mechanisms. Exploring the interactions between Tat and opioids on the GABAergic system may help to guide future research on HAND in the context of opiate drug use.

  7. Spontaneous body movements in spatial cognition

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    Sergiu eTcaci Popescu

    2012-05-01

    Full Text Available People often perform spontaneous body movements during spatial tasks such as giving complex directions or orienting themselves on maps. How are these spontaneous gestures related to spatial problem-solving? We measured spontaneous movements during a perspective-taking task inspired by map reading. Analyzing the motion data to isolate rotation and translation components of motion in specific geometric relation to the task, we found out that most participants executed spontaneous miniature rotations of the head that were significantly related to the main task parameter. These head rotations were as if participants were trying to align themselves with the orientation on the map either in the image plane or on the ground plane, but with tiny amplitudes, typically below 1% of the actual movements. Our results are consistent with a model of sensorimotor prediction driving spatial reasoning. The efference copy of planned movements triggers this prediction mechanism. The movements themselves may then be mostly inhibited; the small spontaneous gestures that we measure are the visible traces of these planned but inhibited actions.

  8. iPSCs: A Minireview from Bench to Bed, including Organoids and the CRISPR System

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    Andrés Javier Orqueda

    2016-01-01

    Full Text Available When Dolly the sheep was born, the first probe into an adult mammalian genome traveling back in time and generating a whole new animal appeared. Ten years later, the reprogramming process became a defined method of producing induced pluripotent stem cells (iPSCs through the overexpression of four transcription factors. iPSCs are capable of originating virtually all types of cells and tissues, including a whole new animal. The reprogramming strategies based on patient-derived cells should make the development of clinical applications of cell based therapy much more straightforward. Here, we analyze the current state, opportunities, and challenges of iPSCs from bench to bed, including organoids and the CRISPR system.

  9. Flexible adaptation of male germ cells from female iPSCs of endangered Tokudaia osimensis.

    Science.gov (United States)

    Honda, Arata; Choijookhuu, Narantsog; Izu, Haruna; Kawano, Yoshihiro; Inokuchi, Mizuho; Honsho, Kimiko; Lee, Ah-Reum; Nabekura, Hiroki; Ohta, Hiroshi; Tsukiyama, Tomoyuki; Ohinata, Yasuhide; Kuroiwa, Asato; Hishikawa, Yoshitaka; Saitou, Mitinori; Jogahara, Takamichi; Koshimoto, Chihiro

    2017-05-01

    In mammals, the Y chromosome strictly influences the maintenance of male germ cells. Almost all mammalian species require genetic contributors to generate testes. An endangered species, Tokudaia osimensis , has a unique sex chromosome composition XO/XO, and genetic differences between males and females have not been confirmed. Although a distinctive sex-determining mechanism may exist in T. osimensis , it has been difficult to examine thoroughly in this rare animal species. To elucidate the discriminative sex-determining mechanism in T. osimensis and to find a strategy to prevent its possible extinction, we have established induced pluripotent stem cells (iPSCs) and derived interspecific chimeras using mice as the hosts and recipients. Generated iPSCs are considered to be in the so-called "true naïve" state, and T. osimensis iPSCs may contribute as interspecific chimeras to several different tissues and cells in live animals. Surprisingly, female T. osimensis iPSCs not only contributed to the female germ line in the interspecific mouse ovary but also differentiated into spermatocytes and spermatids that survived in the adult interspecific mouse testes. Thus, T. osimensis cells have high sexual plasticity through which female somatic cells can be converted to male germline cells. These findings suggest flexibility in T. osimensis cells, which can adapt their germ cell sex to the gonadal niche. The probable reduction of the extinction risk of an endangered species through the use of iPSCs is indicated by this study.

  10. Gender Differences in Global but Not Targeted Demethylation in iPSC Reprogramming

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    Inês Milagre

    2017-01-01

    Full Text Available Global DNA demethylation is an integral part of reprogramming processes in vivo and in vitro, but whether it occurs in the derivation of induced pluripotent stem cells (iPSCs is not known. Here, we show that iPSC reprogramming involves both global and targeted demethylation, which are separable mechanistically and by their biological outcomes. Cells at intermediate-late stages of reprogramming undergo transient genome-wide demethylation, which is more pronounced in female cells. Global demethylation requires activation-induced cytidine deaminase (AID-mediated downregulation of UHRF1 protein, and abolishing demethylation leaves thousands of hypermethylated regions in the iPSC genome. Independently of AID and global demethylation, regulatory regions, particularly ESC enhancers and super-enhancers, are specifically targeted for hypomethylation in association with transcription of the pluripotency network. Our results show that global and targeted DNA demethylation are conserved and distinct reprogramming processes, presumably because of their respective roles in epigenetic memory erasure and in the establishment of cell identity.

  11. Human pancreatic islet-derived extracellular vesicles modulate insulin expression in 3D-differentiating iPSC clusters.

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    Diana Ribeiro

    Full Text Available It has been suggested that extracellular vesicles (EVs can mediate crosstalk between hormones and metabolites within pancreatic tissue. However, the possible effect of pancreatic EVs on stem cell differentiation into pancreatic lineages remains unknown. Herein, human islet-derived EVs (h-Islet-EVs were isolated, characterized and subsequently added to human induced pluripotent stem cell (iPSC clusters during pancreatic differentiation. The h-islet-EVs had a mean size of 117±7 nm and showed positive expression of CD63 and CD81 EV markers as measured by ELISA. The presence of key pancreatic transcription factor mRNA, such as NGN3, MAFA and PDX1, and pancreatic hormone proteins such as C-peptide and glucagon, were confirmed in h-Islet-EVs. iPSC clusters were differentiated in suspension and at the end stages of the differentiation protocol, the mRNA expression of the main pancreatic transcription factors and pancreatic hormones was increased. H-Islet-EVs were supplemented to the iPSC clusters in the later stages of differentiation. It was observed that h-Islet-EVs were able to up-regulate the intracellular levels of C-peptide in iPSC clusters in a concentration-dependent manner. The effect of h-Islet-EVs on the differentiation of iPSC clusters cultured in 3D-collagen hydrogels was also assessed. Although increased mRNA expression for pancreatic markers was observed when culturing the iPSC clusters in 3D-collagen hydrogels, delivery of EVs did not affect the insulin or C-peptide intracellular content. Our results provide new information on the role of h-Islet-EVs in the regulation of insulin expression in differentiating iPSC clusters, and are highly relevant for pancreatic tissue engineering applications.

  12. Generation of Functional Cardiomyocytes from Efficiently Generated Human iPSCs and a Novel Method of Measuring Contractility.

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    Sheeja Rajasingh

    Full Text Available Human induced pluripotent stem cells (iPSCs derived cardiomyocytes (iCMCs would provide an unlimited cell source for regenerative medicine and drug discoveries. The objective of our study is to generate functional cardiomyocytes from human iPSCs and to develop a novel method of measuring contractility of CMCs. In a series of experiments, adult human skin fibroblasts (HSF and human umbilical vein endothelial cells (HUVECs were treated with a combination of pluripotent gene DNA and mRNA under specific conditions. The iPSC colonies were identified and differentiated into various cell lineages, including CMCs. The contractile activity of CMCs was measured by a novel method of frame-by-frame cross correlation (particle image velocimetry-PIV analysis. Our treatment regimen transformed 4% of HSFs into iPSC colonies at passage 0, a significantly improved efficiency compared with use of either DNA or mRNA alone. The iPSCs were capable of differentiating both in vitro and in vivo into endodermal, ectodermal and mesodermal cells, including CMCs with >88% of cells being positive for troponin T (CTT and Gata4 by flow cytometry. We report a highly efficient combination of DNA and mRNA to generate iPSCs and functional iCMCs from adult human cells. We also report a novel approach to measure contractility of iCMCs.

  13. Generation of Functional Cardiomyocytes from Efficiently Generated Human iPSCs and a Novel Method of Measuring Contractility.

    Science.gov (United States)

    Rajasingh, Sheeja; Thangavel, Jayakumar; Czirok, Andras; Samanta, Saheli; Roby, Katherine F; Dawn, Buddhadeb; Rajasingh, Johnson

    2015-01-01

    Human induced pluripotent stem cells (iPSCs) derived cardiomyocytes (iCMCs) would provide an unlimited cell source for regenerative medicine and drug discoveries. The objective of our study is to generate functional cardiomyocytes from human iPSCs and to develop a novel method of measuring contractility of CMCs. In a series of experiments, adult human skin fibroblasts (HSF) and human umbilical vein endothelial cells (HUVECs) were treated with a combination of pluripotent gene DNA and mRNA under specific conditions. The iPSC colonies were identified and differentiated into various cell lineages, including CMCs. The contractile activity of CMCs was measured by a novel method of frame-by-frame cross correlation (particle image velocimetry-PIV) analysis. Our treatment regimen transformed 4% of HSFs into iPSC colonies at passage 0, a significantly improved efficiency compared with use of either DNA or mRNA alone. The iPSCs were capable of differentiating both in vitro and in vivo into endodermal, ectodermal and mesodermal cells, including CMCs with >88% of cells being positive for troponin T (CTT) and Gata4 by flow cytometry. We report a highly efficient combination of DNA and mRNA to generate iPSCs and functional iCMCs from adult human cells. We also report a novel approach to measure contractility of iCMCs.

  14. CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs.

    Science.gov (United States)

    Wang, Lixia; Yi, Fei; Fu, Lina; Yang, Jiping; Wang, Si; Wang, Zhaoxia; Suzuki, Keiichiro; Sun, Liang; Xu, Xiuling; Yu, Yang; Qiao, Jie; Belmonte, Juan Carlos Izpisua; Yang, Ze; Yuan, Yun; Qu, Jing; Liu, Guang-Hui

    2017-05-01

    Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with cellular and molecular mechanisms yet to be fully described. Mutations in a number of genes including SOD1 and FUS are associated with familial ALS. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts of familial ALS patients bearing SOD1 +/A272C and FUS +/G1566A mutations, respectively. We further generated gene corrected ALS iPSCs using CRISPR/Cas9 system. Genome-wide RNA sequencing (RNA-seq) analysis of motor neurons derived from SOD1 +/A272C and corrected iPSCs revealed 899 aberrant transcripts. Our work may shed light on discovery of early biomarkers and pathways dysregulated in ALS, as well as provide a basis for novel therapeutic strategies to treat ALS.

  15. Normal Collagen and Bone Production by Gene-targeted Human Osteogenesis Imperfecta iPSCs

    Science.gov (United States)

    Deyle, David R; Khan, Iram F; Ren, Gaoying; Wang, Pei-Rong; Kho, Jordan; Schwarze, Ulrike; Russell, David W

    2012-01-01

    Osteogenesis imperfecta (OI) is caused by dominant mutations in the type I collagen genes. In principle, the skeletal abnormalities of OI could be treated by transplantation of patient-specific, bone-forming cells that no longer express the mutant gene. Here, we develop this approach by isolating mesenchymal cells from OI patients, inactivating their mutant collagen genes by adeno-associated virus (AAV)-mediated gene targeting, and deriving induced pluripotent stem cells (iPSCs) that were expanded and differentiated into mesenchymal stem cells (iMSCs). Gene-targeted iMSCs produced normal collagen and formed bone in vivo, but were less senescent and proliferated more than bone-derived MSCs. To generate iPSCs that would be more appropriate for clinical use, the reprogramming and selectable marker transgenes were removed by Cre recombinase. These results demonstrate that the combination of gene targeting and iPSC derivation can be used to produce potentially therapeutic cells from patients with genetic disease. PMID:22031238

  16. Nuclear Energy Advanced Modeling and Simulation (NEAMS) Waste Integrated Performance and Safety Codes (IPSC) : FY10 development and integration.

    Energy Technology Data Exchange (ETDEWEB)

    Criscenti, Louise Jacqueline; Sassani, David Carl; Arguello, Jose Guadalupe, Jr.; Dewers, Thomas A.; Bouchard, Julie F.; Edwards, Harold Carter; Freeze, Geoffrey A.; Wang, Yifeng; Schultz, Peter Andrew

    2011-02-01

    This report describes the progress in fiscal year 2010 in developing the Waste Integrated Performance and Safety Codes (IPSC) in support of the U.S. Department of Energy (DOE) Office of Nuclear Energy Advanced Modeling and Simulation (NEAMS) Campaign. The goal of the Waste IPSC is to develop an integrated suite of computational modeling and simulation capabilities to quantitatively assess the long-term performance of waste forms in the engineered and geologic environments of a radioactive waste storage or disposal system. The Waste IPSC will provide this simulation capability (1) for a range of disposal concepts, waste form types, engineered repository designs, and geologic settings, (2) for a range of time scales and distances, (3) with appropriate consideration of the inherent uncertainties, and (4) in accordance with robust verification, validation, and software quality requirements. Waste IPSC activities in fiscal year 2010 focused on specifying a challenge problem to demonstrate proof of concept, developing a verification and validation plan, and performing an initial gap analyses to identify candidate codes and tools to support the development and integration of the Waste IPSC. The current Waste IPSC strategy is to acquire and integrate the necessary Waste IPSC capabilities wherever feasible, and develop only those capabilities that cannot be acquired or suitably integrated, verified, or validated. This year-end progress report documents the FY10 status of acquisition, development, and integration of thermal-hydrologic-chemical-mechanical (THCM) code capabilities, frameworks, and enabling tools and infrastructure.

  17. CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs

    Directory of Open Access Journals (Sweden)

    Lixia Wang

    2017-04-01

    Full Text Available Abstract Amyotrophic lateral sclerosis (ALS is a complex neurodegenerative disease with cellular and molecular mechanisms yet to be fully described. Mutations in a number of genes including SOD1 and FUS are associated with familial ALS. Here we report the generation of induced pluripotent stem cells (iPSCs from fibroblasts of familial ALS patients bearing SOD1 +/A272C and FUS +/G1566A mutations, respectively. We further generated gene corrected ALS iPSCs using CRISPR/Cas9 system. Genome-wide RNA sequencing (RNA-seq analysis of motor neurons derived from SOD1 +/A272C and corrected iPSCs revealed 899 aberrant transcripts. Our work may shed light on discovery of early biomarkers and pathways dysregulated in ALS, as well as provide a basis for novel therapeutic strategies to treat ALS.

  18. Induced pluripotent stem cells (iPSCs) derived from different cell sources and their potential for regenerative and personalized medicine.

    Science.gov (United States)

    Shtrichman, R; Germanguz, I; Itskovitz-Eldor, J

    2013-06-01

    Human induced pluripotent stem cells (hiPSCs) have great potential as a robust source of progenitors for regenerative medicine. The novel technology also enables the derivation of patient-specific cells for applications to personalized medicine, such as for personal drug screening and toxicology. However, the biological characteristics of iPSCs are not yet fully understood and their similarity to human embryonic stem cells (hESCs) is still unresolved. Variations among iPSCs, resulting from their original tissue or cell source, and from the experimental protocols used for their derivation, significantly affect epigenetic properties and differentiation potential. Here we review the potential of iPSCs for regenerative and personalized medicine, and assess their expression pattern, epigenetic memory and differentiation capabilities in relation to their parental tissue source. We also summarize the patient-specific iPSCs that have been derived for applications in biological research and drug discovery; and review risks that must be overcome in order to use iPSC technology for clinical applications.

  19. A time course analysis of the electrophysiological properties of neurons differentiated from human induced pluripotent stem cells (iPSCs.

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    Deborah Prè

    Full Text Available Many protocols have been designed to differentiate human embryonic stem cells (ESCs and human induced pluripotent stem cells (iPSCs into neurons. Despite the relevance of electrophysiological properties for proper neuronal function, little is known about the evolution over time of important neuronal electrophysiological parameters in iPSC-derived neurons. Yet, understanding the development of basic electrophysiological characteristics of iPSC-derived neurons is critical for evaluating their usefulness in basic and translational research. Therefore, we analyzed the basic electrophysiological parameters of forebrain neurons differentiated from human iPSCs, from day 31 to day 55 after the initiation of neuronal differentiation. We assayed the developmental progression of various properties, including resting membrane potential, action potential, sodium and potassium channel currents, somatic calcium transients and synaptic activity. During the maturation of iPSC-derived neurons, the resting membrane potential became more negative, the expression of voltage-gated sodium channels increased, the membrane became capable of generating action potentials following adequate depolarization and, at day 48-55, 50% of the cells were capable of firing action potentials in response to a prolonged depolarizing current step, of which 30% produced multiple action potentials. The percentage of cells exhibiting miniature excitatory post-synaptic currents increased over time with a significant increase in their frequency and amplitude. These changes were associated with an increase of Ca2+ transient frequency. Co-culturing iPSC-derived neurons with mouse glial cells enhanced the development of electrophysiological parameters as compared to pure iPSC-derived neuronal cultures. This study demonstrates the importance of properly evaluating the electrophysiological status of the newly generated neurons when using stem cell technology, as electrophysiological properties of

  20. Proteinuria and lipoprotein lipase activity in Miniature Schnauzer dogs with and without hypertriglyceridemia.

    Science.gov (United States)

    Furrow, E; Jaeger, J Q; Parker, V J; Hinchcliff, K W; Johnson, S E; Murdoch, S J; de Boer, I H; Sherding, R G; Brunzell, J D

    2016-06-01

    Spontaneous hyperlipidemia in rats causes glomerular disease. Idiopathic hypertriglyceridemia (HTG) is prevalent in Miniature Schnauzers, but its relationship with proteinuria is unknown. Decreased activity of major lipid metabolism enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL), may play a role in the cyclic relationship between hyperlipidemia and proteinuria. These enzymes have also not been previously investigated in Miniature Schnauzers. The aims of this study were to determine the relationship between HTG and proteinuria in Miniature Schnauzers and to measure LPL and HL activities in a subset of dogs. Fifty-seven Miniature Schnauzers were recruited (34 with and 23 without HTG). Fasting serum triglyceride concentrations and urine protein-to-creatinine ratios (UPC) were measured in all dogs, and LPL and HL activities were determined in 17 dogs (8 with and 9 without HTG). There was a strong positive correlation between triglyceride concentration and UPC (r = 0.77-0.83, P Schnauzers and could be due to lipid-induced glomerular injury. Reduced LPL activity may contribute to the severity of HTG, but further assay validation is required. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Rapid Generation of Human Genetic Loss-of-Function iPSC Lines by Simultaneous Reprogramming and Gene Editing

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    Andrew M. Tidball

    2017-09-01

    Full Text Available Specifically ablating genes in human induced pluripotent stem cells (iPSCs allows for studies of gene function as well as disease mechanisms in disorders caused by loss-of-function (LOF mutations. While techniques exist for engineering such lines, we have developed and rigorously validated a method of simultaneous iPSC reprogramming while generating CRISPR/Cas9-dependent insertions/deletions (indels. This approach allows for the efficient and rapid formation of genetic LOF human disease cell models with isogenic controls. The rate of mutagenized lines was strikingly consistent across experiments targeting four different human epileptic encephalopathy genes and a metabolic enzyme-encoding gene, and was more efficient and consistent than using CRISPR gene editing of established iPSC lines. The ability of our streamlined method to reproducibly generate heterozygous and homozygous LOF iPSC lines with passage-matched isogenic controls in a single step provides for the rapid development of LOF disease models with ideal control lines, even in the absence of patient tissue.

  2. A simple and efficient feeder-free culture system to up-scale iPSCs on polymeric material surface for use in 3D bioprinting.

    Science.gov (United States)

    Wong, Chui-Wei; Chen, You-Tzung; Chien, Chung-Liang; Yu, Tien-Yu; Rwei, Syang-Peng; Hsu, Shan-Hui

    2018-01-01

    The 3D bioprinting and cell/tissue printing techniques open new possibilities for future applications. To facilitate the 3D bioprinting process, a large amount of living cells are required. Induced pluripotent stem cells (iPSCs) represent a promising cell source for bioprinting. However, the maintenance and expansion of undifferentiated iPSCs are expensive and time consuming. Therefore, in this study a culture method to obtain a sufficient amount of healthy and undifferentiated iPSCs in a short-term period was established. The iPSCs could be passaged for twice on tissue culture polystyrene (TCPS) dish with the conditional medium and could adapt to the feeder-free environment. Feeder-free dishes were further prepared from chitosan, chitosan-hyaluronan, silk fibroin, and polyurethane (PU1 and PU2) two-dimensional substrates. The iPSCs cultured on the chitosan substrates showed a higher proliferation rate without losing the stemness feature. Among the different materials, PU2 could be prepared as a thermoresponsive hydrogel, which was a potential ink for 3D bioprinting. The iPSCs cultured on PU2 substrates well survived when further embedded in PU2 hydrogel. Moreover, PU2 hydrogel printed with iPSCs remained structural integrity. The use of PU2 hydrogel to embed iPSCs reduced the injury to iPSCs by shear stress. These results indicate that iPSCs could be expanded on chitosan or PU2 membranes without the feeder layer and then printed in PU2 hydrogel. The combination of these steps could offer a new possibility for future applications of iPSC-based 3D bioprinting in tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Serotonin increases synaptic activity in olfactory bulb glomeruli.

    Science.gov (United States)

    Brill, Julia; Shao, Zuoyi; Puche, Adam C; Wachowiak, Matt; Shipley, Michael T

    2016-03-01

    Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range. Copyright © 2016 the American Physiological Society.

  4. Global synchronization algorithms for the Intel iPSC/860

    Science.gov (United States)

    Seidel, Steven R.; Davis, Mark A.

    1992-01-01

    In a distributed memory multicomputer that has no global clock, global processor synchronization can only be achieved through software. Global synchronization algorithms are used in tridiagonal systems solvers, CFD codes, sequence comparison algorithms, and sorting algorithms. They are also useful for event simulation, debugging, and for solving mutual exclusion problems. For the Intel iPSC/860 in particular, global synchronization can be used to ensure the most effective use of the communication network for operations such as the shift, where each processor in a one-dimensional array or ring concurrently sends a message to its right (or left) neighbor. Three global synchronization algorithms are considered for the iPSC/860: the gysnc() primitive provided by Intel, the PICL primitive sync0(), and a new recursive doubling synchronization (RDS) algorithm. The performance of these algorithms is compared to the performance predicted by communication models of both the long and forced message protocols. Measurements of the cost of shift operations preceded by global synchronization show that the RDS algorithm always synchronizes the nodes more precisely and costs only slightly more than the other two algorithms.

  5. Synthetic ciguatoxin CTX 3C induces a rapid imbalance in neuronal excitability.

    Science.gov (United States)

    Martín, Victor; Vale, Carmen; Hirama, Masahiro; Yamashita, Shuji; Rubiolo, Juan Andrés; Vieytes, Mercedes R; Botana, Luis M

    2015-06-15

    Ciguatera is a human global disease caused by the consumption of contaminated fish that have accumulated ciguatoxins (CTXs), sodium channel activator toxins. Symptoms of ciguatera include neurological alterations such as paraesthesiae, dysaesthesiae, depression, and heightened nociperception, among others. An important issue to understand these long-term neurological alterations is to establish the role that changes in activity produced by CTX 3C represent to neurons. Here, the effects of synthetic ciguatoxin CTX 3C on membrane potential, spontaneous spiking, and properties of synaptic transmission in cultured cortical neurons of 11-18 days in vitro (DIV) were evaluated using electrophysiological approaches. CTX 3C induced a large depolarization that decreased neuronal firing and caused a rapid inward tonic current that was primarily GABAergic. Moreover, the toxin enhanced the amplitude of miniature postsynaptic inhibitory currents (mIPSCs), whereas it decreased the amplitude of miniature postsynaptic excitatory currents (mEPSCs). The frequency of mIPSCs increased, whereas the frequency of mEPSCs remained unaltered. We describe, for the first time, that a rapid membrane depolarization caused by CTX 3C in cortical neurons activates mechanisms that tend to suppress electrical activity by shifting the balance between excitatory and inhibitory synaptic transmission toward inhibition. Indeed, these results suggest that the acute effects of CTX on synaptic transmission could underlie some of the neurological symptoms caused by ciguatera in humans.

  6. Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs.

    Science.gov (United States)

    Fu, Lina; Xu, Xiuling; Ren, Ruotong; Wu, Jun; Zhang, Weiqi; Yang, Jiping; Ren, Xiaoqing; Wang, Si; Zhao, Yang; Sun, Liang; Yu, Yang; Wang, Zhaoxia; Yang, Ze; Yuan, Yun; Qiao, Jie; Izpisua Belmonte, Juan Carlos; Qu, Jing; Liu, Guang-Hui

    2016-03-01

    Xeroderma pigmentosum (XP) is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patient-specific induced pluripotent stem cells (iPSCs) harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells (NSCs) or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clarify the molecular mechanisms of neurological abnormalities in the XP patients.

  7. Modeling the autistic cell: iPSCs recapitulate developmental principles of syndromic and nonsyndromic ASD.

    Science.gov (United States)

    Ben-Reuven, Lihi; Reiner, Orly

    2016-06-01

    The opportunity to model autism spectrum disorders (ASD) through generation of patient-derived induced pluripotent stem cells (iPSCs) is currently an emerging topic. Wide-scale research of altered brain circuits in syndromic ASD, including Rett Syndrome, Fragile X Syndrome, Angelman's Syndrome and sporadic Schizophrenia, was made possible through animal models. However, possibly due to species differences, and to the possible contribution of epigenetics in the pathophysiology of these diseases, animal models fail to recapitulate many aspects of ASD. With the advent of iPSCs technology, 3D cultures of patient-derived cells are being used to study complex neuronal phenotypes, including both syndromic and nonsyndromic ASD. Here, we review recent advances in using iPSCs to study various aspects of the ASD neuropathology, with emphasis on the efforts to create in vitro model systems for syndromic and nonsyndromic ASD. We summarize the main cellular activity phenotypes and aberrant genetic interaction networks that were found in iPSC-derived neurons of syndromic and nonsyndromic autistic patients. © 2016 Japanese Society of Developmental Biologists.

  8. Vesicular GABA Uptake Can Be Rate Limiting for Recovery of IPSCs from Synaptic Depression

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    Manami Yamashita

    2018-03-01

    Full Text Available Summary: Synaptic efficacy plays crucial roles in neuronal circuit operation and synaptic plasticity. Presynaptic determinants of synaptic efficacy are neurotransmitter content in synaptic vesicles and the number of vesicles undergoing exocytosis at a time. Bursts of presynaptic firings depress synaptic efficacy, mainly due to depletion of releasable vesicles, whereas recovery from strong depression is initiated by endocytic vesicle retrieval followed by refilling of vesicles with neurotransmitter. We washed out presynaptic cytosolic GABA to induce a rundown of IPSCs at cerebellar inhibitory cell pairs in slices from rats and then allowed fast recovery by elevating GABA concentration using photo-uncaging. The time course of this recovery coincided with that of IPSCs from activity-dependent depression induced by a train of high-frequency stimulation. We conclude that vesicular GABA uptake can be a limiting step for the recovery of inhibitory neurotransmission from synaptic depression. : Recovery of inhibitory synaptic transmission from activity-dependent depression requires refilling of vesicles with GABA. Yamashita et al. find that vesicular uptake rate of GABA is a slow process, limiting the recovery rate of IPSCs from depression.

  9. Generation of iPSC line from desmin-related cardiomyopathy patient carrying splice site mutation of DES gene

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    Aleksandr Khudiakov

    2017-10-01

    Full Text Available Human iPSC line was generated from patient-specific adipose tissue-derived mesenchymal multipotent stromal cells carrying desmin (DES gene heterozygous splice site mutation using non-integrative reprogramming method. Reprogramming factors OCT4, KLF4, SOX2, CMYC were delivered using Sendai viruses. iPSCs were characterized by sequencing, karyotype analysis, STR analysis, immunocytochemistry, RT-PCR and teratoma formation.

  10. Aged induced pluripotent stem cell (iPSCs) as a new cellular model for studying premature aging.

    Science.gov (United States)

    Petrini, Stefania; Borghi, Rossella; D'Oria, Valentina; Restaldi, Fabrizia; Moreno, Sandra; Novelli, Antonio; Bertini, Enrico; Compagnucci, Claudia

    2017-05-31

    Nuclear integrity and mechanical stability of the nuclear envelope (NE) are conferred by the nuclear lamina, a meshwork of intermediate filaments composed of A- and B-type lamins, supporting the inner nuclear membrane and playing a pivotal role in chromatin organization and epigenetic regulation. During cell senescence, nuclear alterations also involving NE architecture are widely described. In the present study, we utilized induced pluripotent stem cells (iPSCs) upon prolonged in vitro culture as a model to study aging and investigated the organization and expression pattern of NE major constituents. Confocal and four-dimensional imaging combined with molecular analyses, showed that aged iPSCs are characterized by nuclear dysmorphisms, nucleoskeletal components (lamin A/C-prelamin isoforms, lamin B1, emerin, and nesprin-2) imbalance, leading to impaired nucleo-cytoplasmic MKL1 shuttling, actin polymerization defects, mitochondrial dysfunctions, SIRT7 downregulation and NF-kBp65 hyperactivation. The observed age-related NE features of iPSCs closely resemble those reported for premature aging syndromes (e.g., Hutchinson-Gilford progeria syndrome) and for somatic cell senescence. These findings validate the use of aged iPSCs as a suitable cellular model to study senescence and for investigating therapeutic strategies aimed to treat premature aging.

  11. Communication overhead on the Intel iPSC-860 hypercube

    Science.gov (United States)

    Bokhari, Shahid H.

    1990-01-01

    Experiments were conducted on the Intel iPSC-860 hypercube in order to evaluate the overhead of interprocessor communication. It is demonstrated that: (1) contrary to popular belief, the distance between two communicating processors has a significant impact on communication time, (2) edge contention can increase communication time by a factor of more than 7, and (3) node contention has no measurable impact.

  12. Efficient differentiation of steroidogenic and germ-like cells from epigenetically-related iPSCs derived from ovarian granulosa cells.

    Directory of Open Access Journals (Sweden)

    Raymond Anchan

    Full Text Available To explore restoration of ovarian function using epigenetically-related, induced pluripotent stem cells (iPSCs, we functionally evaluated the epigenetic memory of novel iPSC lines, derived from mouse and human ovarian granulosa cells (GCs using c-Myc, Klf4, Sox2 and Oct4 retroviral vectors. The stem cell identity of the mouse and human GC-derived iPSCs (mGriPSCs, hGriPSCs was verified by demonstrating embryonic stem cell (ESC antigen expression using immunocytochemistry and RT-PCR analysis, as well as formation of embryoid bodies (EBs and teratomas that are capable of differentiating into cells from all three germ layers. GriPSCs' gene expression profiles associate more closely with those of ESCs than of the originating GCs as demonstrated by genome-wide analysis of mRNA and microRNA. A comparative analysis of EBs generated from three different mouse cell lines (mGriPSCs; fibroblast-derived iPSC, mFiPSCs; G4 embryonic stem cells, G4 mESCs revealed that differentiated mGriPSC-EBs synthesize 10-fold more estradiol (E2 than either differentiated FiPSC- or mESC-EBs under identical culture conditions. By contrast, mESC-EBs primarily synthesize progesterone (P4 and FiPSC-EBs produce neither E2 nor P4. Differentiated mGriPSC-EBs also express ovarian markers (AMHR, FSHR, Cyp19a1, ER and Inha as well as markers of early gametogenesis (Mvh, Dazl, Gdf9, Boule and Zp1 more frequently than EBs of the other cell lines. These results provide evidence of preferential homotypic differentiation of mGriPSCs into ovarian cell types. Collectively, our data support the hypothesis that generating iPSCs from the desired tissue type may prove advantageous due to the iPSCs' epigenetic memory.

  13. Optogenetic release of ACh induces rhythmic bursts of perisomatic IPSCs in hippocampus.

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    Daniel A Nagode

    Full Text Available Acetylcholine (ACh influences a vast array of phenomena in cortical systems. It alters many ionic conductances and neuronal firing behavior, often by regulating membrane potential oscillations in populations of cells. Synaptic inhibition has crucial roles in many forms of oscillation, and cholinergic mechanisms regulate both oscillations and synaptic inhibition. In vitro investigations using bath-application of cholinergic receptor agonists, or bulk tissue electrical stimulation to release endogenous ACh, have led to insights into cholinergic function, but questions remain because of the relative lack of selectivity of these forms of stimulation. To investigate the effects of selective release of ACh on interneurons and oscillations, we used an optogenetic approach in which the light-sensitive non-selective cation channel, Channelrhodopsin2 (ChR2, was virally delivered to cholinergic projection neurons in the medial septum/diagonal band of Broca (MS/DBB of adult mice expressing Cre-recombinase under the control of the choline-acetyltransferase (ChAT promoter. Acute hippocampal slices obtained from these animals weeks later revealed ChR2 expression in cholinergic axons. Brief trains of blue light pulses delivered to untreated slices initiated bursts of ACh-evoked, inhibitory post-synaptic currents (L-IPSCs in CA1 pyramidal cells that lasted for 10's of seconds after the light stimulation ceased. L-IPSC occurred more reliably in slices treated with eserine and a very low concentration of 4-AP, which were therefore used in most experiments. The rhythmic, L-IPSCs were driven primarily by muscarinic ACh receptors (mAChRs, and could be suppressed by endocannabinoid release from pyramidal cells. Finally, low-frequency oscillations (LFOs of local field potentials (LFPs were significantly cross-correlated with the L-IPSCs, and reversal of the LFPs near s. pyramidale confirmed that the LFPs were driven by perisomatic inhibition. This optogenetic approach

  14. Hepatic differentiation of human pluripotent stem cells in miniaturized format suitable for high-throughput screen

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    Arnaud Carpentier

    2016-05-01

    Full Text Available The establishment of protocols to differentiate human pluripotent stem cells (hPSCs including embryonic (ESC and induced pluripotent (iPSC stem cells into functional hepatocyte-like cells (HLCs creates new opportunities to study liver metabolism, genetic diseases and infection of hepatotropic viruses (hepatitis B and C viruses in the context of specific genetic background. While supporting efficient differentiation to HLCs, the published protocols are limited in terms of differentiation into fully mature hepatocytes and in a smaller-well format. This limitation handicaps the application of these cells to high-throughput assays. Here we describe a protocol allowing efficient and consistent hepatic differentiation of hPSCs in 384-well plates into functional hepatocyte-like cells, which remain differentiated for more than 3 weeks. This protocol affords the unique opportunity to miniaturize the hPSC-based differentiation technology and facilitates screening for molecules in modulating liver differentiation, metabolism, genetic network, and response to infection or other external stimuli.

  15. Generation of human iPSC line from a patient with laterality defects and associated congenital heart anomalies carrying a DAND5 missense alteration

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    Fernando Cristo

    2017-12-01

    Full Text Available A human iPSC line was generated from exfoliated renal epithelial (ERE cells of a patient affected with Congenital Heart Disease (CHD and Laterality Defects carrying tshe variant p.R152H in the DAND5 gene. The transgene-free iPSCs were generated with the human OSKM transcription factor using the Sendai-virus reprogramming system. The established iPSC line had the specific heterozygous alteration, a stable karyotype, expressed pluripotency markers and generated embryoid bodies that can differentiate towards the three germ layers in vitro. This iPSC line offers a useful resource to study the molecular mechanisms of cardiomyocyte proliferation, as well as for drug testing.

  16. Lipid Supplement in the Cultural Condition Facilitates the Porcine iPSC Derivation through cAMP/PKA/CREB Signal Pathway

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    Wei Zhang

    2018-02-01

    Full Text Available Large numbers of lipids exist in the porcine oocytes and early embryos and have the positive effects on their development, suggesting that the lipids may play an important role in pluripotency establishment and maintenance in pigs. However, the effects of lipids and their metabolites, such as fatty acids on reprogramming and the pluripotency gene expression of porcine-induced pluripotent stem cells (iPSCs, are unclear. Here, we generated the porcine iPSCs that resemble the mouse embryonic stem cells (ESCs under lipid and fatty-acid-enriched cultural conditions (supplement of AlbuMAX. These porcine iPSCs show positive for the ESCs pluripotency markers and have the differentiation abilities to all three germ layers, and importantly, have the capability of aggregation into the inner cell mass (ICM of porcine blastocysts. We further confirmed that lipid and fatty acid enriched condition can promote the cell proliferation and improve reprogramming efficiency by elevating cAMP levels. Interestingly, this lipids supplement promotes mesenchymal–epithelial transition (MET through the cAMP/PKA/CREB signal pathway and upregulates the E-cadherin expression during porcine somatic cell reprogramming. The lipids supplement also makes a contribution to lipid droplets accumulation in the porcine iPSCs that resemble porcine preimplantation embryos. These findings may facilitate understanding of the lipid metabolism in porcine iPSCs and lay the foundation of bona fide porcine embryonic stem cell derivation.

  17. Concentration-dependent activation of dopamine receptors differentially modulates GABA release onto orexin neurons.

    Science.gov (United States)

    Linehan, Victoria; Trask, Robert B; Briggs, Chantalle; Rowe, Todd M; Hirasawa, Michiru

    2015-08-01

    Dopamine (DA) and orexin neurons play important roles in reward and food intake. There are anatomical and functional connections between these two cell groups: orexin peptides stimulate DA neurons in the ventral tegmental area and DA inhibits orexin neurons in the hypothalamus. However, the cellular mechanisms underlying the action of DA on orexin neurons remain incompletely understood. Therefore, the effect of DA on inhibitory transmission to orexin neurons was investigated in rat brain slices using the whole-cell patch-clamp technique. We found that DA modulated the frequency of spontaneous and miniature IPSCs (mIPSCs) in a concentration-dependent bidirectional manner. Low (1 μM) and high (100 μM) concentrations of DA decreased and increased IPSC frequency, respectively. These effects did not accompany a change in mIPSC amplitude and persisted in the presence of G-protein signaling inhibitor GDPβS in the pipette, suggesting that DA acts presynaptically. The decrease in mIPSC frequency was mediated by D2 receptors whereas the increase required co-activation of D1 and D2 receptors and subsequent activation of phospholipase C. In summary, our results suggest that DA has complex effects on GABAergic transmission to orexin neurons, involving cooperation of multiple receptor subtypes. The direction of dopaminergic influence on orexin neurons is dependent on the level of DA in the hypothalamus. At low levels DA disinhibits orexin neurons whereas at high levels it facilitates GABA release, which may act as negative feedback to curb the excitatory orexinergic output to DA neurons. These mechanisms may have implications for consummatory and motivated behaviours. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  18. iPSCORE: A Resource of 222 iPSC Lines Enabling Functional Characterization of Genetic Variation across a Variety of Cell Types

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    Athanasia D. Panopoulos

    2017-04-01

    Full Text Available Summary: Large-scale collections of induced pluripotent stem cells (iPSCs could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection of systematically derived and characterized iPSC lines from 222 ethnically diverse individuals that allows for both familial and association-based genetic studies. iPSCORE lines are pluripotent with high genomic integrity (no or low numbers of somatic copy-number variants as determined using high-throughput RNA-sequencing and genotyping arrays, respectively. Using iPSCs from a family of individuals, we show that iPSC-derived cardiomyocytes demonstrate gene expression patterns that cluster by genetic background, and can be used to examine variants associated with physiological and disease phenotypes. The iPSCORE collection contains representative individuals for risk and non-risk alleles for 95% of SNPs associated with human phenotypes through genome-wide association studies. Our study demonstrates the utility of iPSCORE for examining how genetic variants influence molecular and physiological traits in iPSCs and derived cell lines. : Working as part of the NHLBI NextGen consortium, Panopoulos and colleagues report the derivation and characterization of 222 publicly available iPSCs from ethnically diverse individuals with corresponding genomic data including SNP arrays, RNA-seq, and whole-genome sequencing. This collection provides a powerful resource to investigate the function of genetic variants. Keywords: iPSCORE, iPSC, GWAS, molecular traits, physiological traits, cardiac disease, NHLBI Next Gen, LQT2, KCNH2, iPSC-derived cardiomyocytes

  19. Human neural progenitors derived from integration-free iPSCs for SCI therapy

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    Ying Liu

    2017-03-01

    Full Text Available As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (iPSCs provide great capability for tissue regeneration, particularly in spinal cord injury (SCI. However, despite significant progress made in translation of iPSC-derived neural progenitor cells (NPCs to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NPCs before transplantation are top priorities to overcome. In this study, we developed a safe and cost-effective pipeline to generate clinically relevant NPCs. We first isolated cells from patients' urine and reprogrammed them into iPSCs by non-integrating Sendai viral vectors, and carried out experiments on neural differentiation. NPCs were purified by A2B5, an antibody specifically recognizing a glycoganglioside on the cell surface of neural lineage cells, via fluorescence activated cell sorting. Upon further in vitro induction, NPCs were able to give rise to neurons, oligodendrocytes and astrocytes. To test the functionality of the A2B5+ NPCs, we grafted them into the contused mouse thoracic spinal cord. Eight weeks after transplantation, the grafted cells survived, integrated into the injured spinal cord, and differentiated into neurons and glia. Our specific focus on cell source, reprogramming, differentiation and purification method purposely addresses timing and safety issues of transplantation to SCI models. It is our belief that this work takes one step closer on using human iPSC derivatives to SCI clinical settings.

  20. Origin-Dependent Neural Cell Identities in Differentiated Human iPSCs In Vitro and after Transplantation into the Mouse Brain

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    Gunnar Hargus

    2014-09-01

    Full Text Available The differentiation capability of induced pluripotent stem cells (iPSCs toward certain cell types for disease modeling and drug screening assays might be influenced by their somatic cell of origin. Here, we have compared the neural induction of human iPSCs generated from fetal neural stem cells (fNSCs, dermal fibroblasts, or cord blood CD34+ hematopoietic progenitor cells. Neural progenitor cells (NPCs and neurons could be generated at similar efficiencies from all iPSCs. Transcriptomics analysis of the whole genome and of neural genes revealed a separation of neuroectoderm-derived iPSC-NPCs from mesoderm-derived iPSC-NPCs. Furthermore, we found genes that were similarly expressed in fNSCs and neuroectoderm, but not in mesoderm-derived iPSC-NPCs. Notably, these neural signatures were retained after transplantation into the cortex of mice and paralleled with increased survival of neuroectoderm-derived cells in vivo. These results indicate distinct origin-dependent neural cell identities in differentiated human iPSCs both in vitro and in vivo.

  1. Modelling urea-cycle disorder citrullinemia type 1 with disease-specific iPSCs.

    Science.gov (United States)

    Yoshitoshi-Uebayashi, Elena Yukie; Toyoda, Taro; Yasuda, Katsutaro; Kotaka, Maki; Nomoto, Keiko; Okita, Keisuke; Yasuchika, Kentaro; Okamoto, Shinya; Takubo, Noriyuki; Nishikubo, Toshiya; Soga, Tomoyoshi; Uemoto, Shinji; Osafune, Kenji

    2017-05-06

    Citrullinemia type 1 (CTLN1) is a urea cycle disorder (UCD) caused by mutations of the ASS1 gene, which is responsible for production of the enzyme argininosuccinate synthetase (ASS), and classically presented as life-threatening hyperammonemia in newborns. Therapeutic options are limited, and neurological sequelae may persist. To understand the pathophysiology and find novel treatments, induced pluripotent stem cells (iPSCs) were generated from a CTLN1 patient and differentiated into hepatocyte-like cells (HLCs). CTLN1-HLCs have lower ureagenesis, recapitulating part of the patient's phenotype. l-arginine, an amino acid clinically used for UCD treatment, improved this phenotype in vitro. Metabolome analysis revealed an increase in tricarboxylic acid (TCA) cycle metabolites in CTLN1, suggesting a connection between CTLN1 and the TCA cycle. This CTLN1-iPSC model improves the understanding of CTLN1 pathophysiology and can be used to pursue new therapeutic approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Generation of retinal pigmented epithelium from iPSCs derived from the conjunctiva of donors with and without age related macular degeneration.

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    Zhouhui Geng

    Full Text Available Fidelity in pluripotent stem cell differentiation protocols is necessary for the therapeutic and commercial use of cells derived from embryonic and induced pluripotent stem cells. Recent advances in stem cell technology, especially the widespread availability of a range of chemically defined media, substrates and differentiation components, now allow the design and implementation of fully defined derivation and differentiation protocols intended for replication across multiple research and manufacturing locations. In this report we present an application of these criteria to the generation of retinal pigmented epithelium from iPSCs derived from the conjunctiva of donors with and without age related macular degeneration. Primary conjunctival cells from human donors aged 70-85 years were reprogrammed to derive multiple iPSC lines that were differentiated into functional RPE using a rapid and defined differentiation protocol. The combination of defined iPSC derivation and culture with a defined RPE differentiation protocol, reproducibly generated functional RPE from each donor without requiring protocol adjustments for each individual. This successful validation of a standardized, iPSC derivation and RPE differentiation process demonstrates a practical approach for applications requiring the cost-effective generation of RPE from multiple individuals such as drug testing, population studies or for therapies requiring patient-specific RPE derivations. In addition, conjunctival cells are identified as a practical source of somatic cells for deriving iPSCs from elderly individuals.

  3. Efficient Generation and Editing of Feeder-free IPSCs from Human Pancreatic Cells Using the CRISPR-Cas9 System.

    Science.gov (United States)

    Nandal, Anjali; Mallon, Barbara; Telugu, Bhanu P

    2017-11-08

    Embryonic and induced pluripotent stem cells can self-renew and differentiate into multiple cell types of the body. The pluripotent cells are thus coveted for research in regenerative medicine and are currently in clinical trials for eye diseases, diabetes, heart diseases, and other disorders. The potential to differentiate into specialized cell types coupled with the recent advances in genome editing technologies including the CRISPR/Cas system have provided additional opportunities for tailoring the genome of iPSC for varied applications including disease modeling, gene therapy, and biasing pathways of differentiation, to name a few. Among the available editing technologies, the CRISPR/Cas9 from Streptococcus pyogenes has emerged as a tool of choice for site-specific editing of the eukaryotic genome. The CRISPRs are easily accessible, inexpensive, and highly efficient in engineering targeted edits. The system requires a Cas9 nuclease and a guide sequence (20-mer) specific to the genomic target abutting a 3-nucleotide "NGG" protospacer-adjacent-motif (PAM) for targeting Cas9 to the desired genomic locus, alongside a universal Cas9 binding tracer RNA (together called single guide RNA or sgRNA). Here we present a step-by-step protocol for efficient generation of feeder-independent and footprint-free iPSC and describe methodologies for genome editing of iPSC using the Cas9 ribonucleoprotein (RNP) complexes. The genome editing protocol is effective and can be easily multiplexed by pre-complexing sgRNAs for more than one target with the Cas9 protein and simultaneously delivering into the cells. Finally, we describe a simplified approach for identification and characterization of iPSCs with desired edits. Taken together, the outlined strategies are expected to streamline generation and editing of iPSC for manifold applications.

  4. One-step genetic correction of hemoglobin E/beta-thalassemia patient-derived iPSCs by the CRISPR/Cas9 system.

    Science.gov (United States)

    Wattanapanitch, Methichit; Damkham, Nattaya; Potirat, Ponthip; Trakarnsanga, Kongtana; Janan, Montira; U-Pratya, Yaowalak; Kheolamai, Pakpoom; Klincumhom, Nuttha; Issaragrisil, Surapol

    2018-02-26

    Thalassemia is the most common genetic disease worldwide; those with severe disease require lifelong blood transfusion and iron chelation therapy. The definitive cure for thalassemia is allogeneic hematopoietic stem cell transplantation, which is limited due to lack of HLA-matched donors and the risk of post-transplant complications. Induced pluripotent stem cell (iPSC) technology offers prospects for autologous cell-based therapy which could avoid the immunological problems. We now report genetic correction of the beta hemoglobin (HBB) gene in iPSCs derived from a patient with a double heterozygote for hemoglobin E and β-thalassemia (HbE/β-thalassemia), the most common thalassemia syndrome in Thailand and Southeast Asia. We used the CRISPR/Cas9 system to target the hemoglobin E mutation from one allele of the HBB gene by homology-directed repair with a single-stranded DNA oligonucleotide template. DNA sequences of the corrected iPSCs were validated by Sanger sequencing. The corrected clones were differentiated into hematopoietic progenitor and erythroid cells to confirm their multilineage differentiation potential and hemoglobin expression. The hemoglobin E mutation of HbE/β-thalassemia iPSCs was seamlessly corrected by the CRISPR/Cas9 system. The corrected clones were differentiated into hematopoietic progenitor cells under feeder-free and OP9 coculture systems. These progenitor cells were further expanded in erythroid liquid culture system and developed into erythroid cells that expressed mature HBB gene and HBB protein. Our study provides a strategy to correct hemoglobin E mutation in one step and these corrected iPSCs can be differentiated into hematopoietic stem cells to be used for autologous transplantation in patients with HbE/β-thalassemia in the future.

  5. Challenge problem and milestones for : Nuclear Energy Advanced Modeling and Simulation (NEAMS) waste Integrated Performance and Safety Codes (IPSC).

    Energy Technology Data Exchange (ETDEWEB)

    Freeze, Geoffrey A.; Wang, Yifeng; Howard, Robert; McNeish, Jerry A.; Schultz, Peter Andrew; Arguello, Jose Guadalupe, Jr.

    2010-09-01

    This report describes the specification of a challenge problem and associated challenge milestones for the Waste Integrated Performance and Safety Codes (IPSC) supporting the U.S. Department of Energy (DOE) Office of Nuclear Energy Advanced Modeling and Simulation (NEAMS) Campaign. The NEAMS challenge problems are designed to demonstrate proof of concept and progress towards IPSC goals. The goal of the Waste IPSC is to develop an integrated suite of modeling and simulation capabilities to quantitatively assess the long-term performance of waste forms in the engineered and geologic environments of a radioactive waste storage or disposal system. The Waste IPSC will provide this simulation capability (1) for a range of disposal concepts, waste form types, engineered repository designs, and geologic settings, (2) for a range of time scales and distances, (3) with appropriate consideration of the inherent uncertainties, and (4) in accordance with robust verification, validation, and software quality requirements. To demonstrate proof of concept and progress towards these goals and requirements, a Waste IPSC challenge problem is specified that includes coupled thermal-hydrologic-chemical-mechanical (THCM) processes that describe (1) the degradation of a borosilicate glass waste form and the corresponding mobilization of radionuclides (i.e., the processes that produce the radionuclide source term), (2) the associated near-field physical and chemical environment for waste emplacement within a salt formation, and (3) radionuclide transport in the near field (i.e., through the engineered components - waste form, waste package, and backfill - and the immediately adjacent salt). The initial details of a set of challenge milestones that collectively comprise the full challenge problem are also specified.

  6. Challenge problem and milestones for: Nuclear Energy Advanced Modeling and Simulation (NEAMS) waste Integrated Performance and Safety Codes (IPSC)

    International Nuclear Information System (INIS)

    Freeze, Geoffrey A.; Wang, Yifeng; Howard, Robert; McNeish, Jerry A.; Schultz, Peter Andrew; Arguello, Jose Guadalupe Jr.

    2010-01-01

    This report describes the specification of a challenge problem and associated challenge milestones for the Waste Integrated Performance and Safety Codes (IPSC) supporting the U.S. Department of Energy (DOE) Office of Nuclear Energy Advanced Modeling and Simulation (NEAMS) Campaign. The NEAMS challenge problems are designed to demonstrate proof of concept and progress towards IPSC goals. The goal of the Waste IPSC is to develop an integrated suite of modeling and simulation capabilities to quantitatively assess the long-term performance of waste forms in the engineered and geologic environments of a radioactive waste storage or disposal system. The Waste IPSC will provide this simulation capability (1) for a range of disposal concepts, waste form types, engineered repository designs, and geologic settings, (2) for a range of time scales and distances, (3) with appropriate consideration of the inherent uncertainties, and (4) in accordance with robust verification, validation, and software quality requirements. To demonstrate proof of concept and progress towards these goals and requirements, a Waste IPSC challenge problem is specified that includes coupled thermal-hydrologic-chemical-mechanical (THCM) processes that describe (1) the degradation of a borosilicate glass waste form and the corresponding mobilization of radionuclides (i.e., the processes that produce the radionuclide source term), (2) the associated near-field physical and chemical environment for waste emplacement within a salt formation, and (3) radionuclide transport in the near field (i.e., through the engineered components - waste form, waste package, and backfill - and the immediately adjacent salt). The initial details of a set of challenge milestones that collectively comprise the full challenge problem are also specified.

  7. Potential of Induced Pluripotent Stem Cells (iPSCs for Treating Age-Related Macular Degeneration (AMD

    Directory of Open Access Journals (Sweden)

    Mark Fields

    2016-12-01

    Full Text Available The field of stem cell biology has rapidly evolved in the last few decades. In the area of regenerative medicine, clinical applications using stem cells hold the potential to be a powerful tool in the treatment of a wide variety of diseases, in particular, disorders of the eye. Embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs are promising technologies that can potentially provide an unlimited source of cells for cell replacement therapy in the treatment of retinal degenerative disorders such as age-related macular degeneration (AMD, Stargardt disease, and other disorders. ESCs and iPSCs have been used to generate retinal pigment epithelium (RPE cells and their functional behavior has been tested in vitro and in vivo in animal models. Additionally, iPSC-derived RPE cells provide an autologous source of cells for therapeutic use, as well as allow for novel approaches in disease modeling and drug development platforms. Clinical trials are currently testing the safety and efficacy of these cells in patients with AMD. In this review, the current status of iPSC disease modeling of AMD is discussed, as well as the challenges and potential of this technology as a viable option for cell replacement therapy in retinal degeneration.

  8. Potential of Induced Pluripotent Stem Cells (iPSCs) for Treating Age-Related Macular Degeneration (AMD).

    Science.gov (United States)

    Fields, Mark; Cai, Hui; Gong, Jie; Del Priore, Lucian

    2016-12-08

    The field of stem cell biology has rapidly evolved in the last few decades. In the area of regenerative medicine, clinical applications using stem cells hold the potential to be a powerful tool in the treatment of a wide variety of diseases, in particular, disorders of the eye. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are promising technologies that can potentially provide an unlimited source of cells for cell replacement therapy in the treatment of retinal degenerative disorders such as age-related macular degeneration (AMD), Stargardt disease, and other disorders. ESCs and iPSCs have been used to generate retinal pigment epithelium (RPE) cells and their functional behavior has been tested in vitro and in vivo in animal models. Additionally, iPSC-derived RPE cells provide an autologous source of cells for therapeutic use, as well as allow for novel approaches in disease modeling and drug development platforms. Clinical trials are currently testing the safety and efficacy of these cells in patients with AMD. In this review, the current status of iPSC disease modeling of AMD is discussed, as well as the challenges and potential of this technology as a viable option for cell replacement therapy in retinal degeneration.

  9. NEAMS Nuclear Waste Management IPSC: evaluation and selection of tools for the quality environment

    International Nuclear Information System (INIS)

    Bouchard, Julie F.; Stubblefield, William Anthony; Vigil, Dena M.; Edwards, Harold Carter

    2011-01-01

    The objective of the U.S. Department of Energy Office of Nuclear Energy Advanced Modeling and Simulation Nuclear Waste Management Integrated Performance and Safety Codes (NEAMS Nuclear Waste Management IPSC) is to provide an integrated suite of computational modeling and simulation (M and S) capabilities to quantitatively assess the long-term performance of waste forms in the engineered and geologic environments of a radioactive-waste storage facility or disposal repository. These M and S capabilities are to be managed, verified, and validated within the NEAMS Nuclear Waste Management IPSC quality environment. M and S capabilities and the supporting analysis workflow and simulation data management tools will be distributed to end-users from this same quality environment. The same analysis workflow and simulation data management tools that are to be distributed to end-users will be used for verification and validation (V and V) activities within the quality environment. This strategic decision reduces the number of tools to be supported, and increases the quality of tools distributed to end users due to rigorous use by V and V activities. This report documents an evaluation of the needs, options, and tools selected for the NEAMS Nuclear Waste Management IPSC quality environment. The objective of the U.S. Department of Energy (DOE) Office of Nuclear Energy Advanced Modeling and Simulation Nuclear Waste Management Integrated Performance and Safety Codes (NEAMS Nuclear Waste Management IPSC) program element is to provide an integrated suite of computational modeling and simulation (M and S) capabilities to assess quantitatively the long-term performance of waste forms in the engineered and geologic environments of a radioactive-waste storage facility or disposal repository. This objective will be fulfilled by acquiring and developing M and S capabilities, and establishing a defensible level of confidence in these M and S capabilities. The foundation for assessing the

  10. Generation of induced pluripotent stem cells (iPSCs) from an Alzheimer's disease patient carrying a L150P mutation in PSEN-1

    DEFF Research Database (Denmark)

    Tubsuwan, Alisa; Pires, Carlota; Rasmussen, Mikkel A.

    2016-01-01

    Induced pluripotent stem cells (iPSCs) were generated from skin fibroblasts isolated from a 58-year old male with a L150P mutation in the presenilin 1 (PSEN-1) gene, which is responsible for the majority of familial cases of Alzheimer's disease (AD). The iPSC swere established by co......-electroporation with episomal plasmids containing hOCT4, hSOX2, hL-MYC, hKLF4, hNANOG, hLIN28, and short hairpin RNA against TP53. The iPSCs contained the specific heterozygous mutation c.449C>T, had normal karyotype, expressed the expected pluripotency genes and displayed in vitro differentiation potential to the three germ...

  11. Rescue of DNA-PK Signaling and T-Cell Differentiation by Targeted Genome Editing in a prkdc Deficient iPSC Disease Model.

    Directory of Open Access Journals (Sweden)

    Shamim H Rahman

    2015-05-01

    Full Text Available In vitro disease modeling based on induced pluripotent stem cells (iPSCs provides a powerful system to study cellular pathophysiology, especially in combination with targeted genome editing and protocols to differentiate iPSCs into affected cell types. In this study, we established zinc-finger nuclease-mediated genome editing in primary fibroblasts and iPSCs generated from a mouse model for radiosensitive severe combined immunodeficiency (RS-SCID, a rare disorder characterized by cellular sensitivity to radiation and the absence of lymphocytes due to impaired DNA-dependent protein kinase (DNA-PK activity. Our results demonstrate that gene editing in RS-SCID fibroblasts rescued DNA-PK dependent signaling to overcome radiosensitivity. Furthermore, in vitro T-cell differentiation from iPSCs was employed to model the stage-specific T-cell maturation block induced by the disease causing mutation. Genetic correction of the RS-SCID iPSCs restored T-lymphocyte maturation, polyclonal V(DJ recombination of the T-cell receptor followed by successful beta-selection. In conclusion, we provide proof that iPSC-based in vitro T-cell differentiation is a valuable paradigm for SCID disease modeling, which can be utilized to investigate disorders of T-cell development and to validate gene therapy strategies for T-cell deficiencies. Moreover, this study emphasizes the significance of designer nucleases as a tool for generating isogenic disease models and their future role in producing autologous, genetically corrected transplants for various clinical applications.

  12. Generation of human iPSCs from an essential thrombocythemia patient carrying a V501L mutation in the MPL gene.

    Science.gov (United States)

    Liu, Senquan; Ye, Zhaohui; Gao, Yongxing; He, Chaoxia; Williams, Donna W; Moliterno, Alison; Spivak, Jerry; Huang, He; Cheng, Linzhao

    2017-01-01

    Activating point mutations in the MPL gene encoding the thrombopoietin receptor are found in 3%-10% of essential thrombocythemia (ET) and myelofibrosis patients. Here, we report the derivation of induced pluripotent stem cells (iPSCs) from an ET patient with a heterozygous MPL V501L mutation. Peripheral blood CD34 + progenitor cells were reprogrammed by transient plasmid expression of OCT4, SOX2, KLF4, c-MYC plus BCL2L1 (BCL-xL) genes. The derived line M494 carries a MPL V501L mutation, displays typical iPSC morphology and characteristics, are pluripotent and karyotypically normal. Upon differentiation, the iPSCs are able to differentiate into cells derived from three germ layers. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  13. One-Step Biallelic and Scarless Correction of a β-Thalassemia Mutation in Patient-Specific iPSCs without Drug Selection

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    Yali Liu

    2017-03-01

    Full Text Available Monogenic disorders (MGDs, which are caused by single gene mutations, have a serious effect on human health. Among these, β-thalassemia (β-thal represents one of the most common hereditary hematological diseases caused by mutations in the human hemoglobin β (HBB gene. The technologies of induced pluripotent stem cells (iPSCs and genetic correction provide insights into the treatments for MGDs, including β-thal. However, traditional approaches for correcting mutations have a low efficiency and leave a residual footprint, which leads to some safety concerns in clinical applications. As a proof of concept, we utilized single-strand oligodeoxynucleotides (ssODNs, high-fidelity CRISPR/Cas9 nuclease, and small molecules to achieve a seamless correction of the β-41/42 (TCTT deletion mutation in β thalassemia patient-specific iPSCs with remarkable efficiency. Additionally, off-target analysis and whole-exome sequencing results revealed that corrected cells exhibited a minimal mutational load and no off-target mutagenesis. When differentiated into hematopoietic progenitor cells (HPCs and then further to erythroblasts, the genetically corrected cells expressed normal β-globin transcripts. Our studies provide the most efficient and safe approach for the genetic correction of the β-41/42 (TCTT deletion in iPSCs for further potential cell therapy of β-thal, which represents a potential therapeutic avenue for the gene correction of MGD-associated mutants in patient-specific iPSCs.

  14. CRISPR Interference Efficiently Induces Specific and Reversible Gene Silencing in Human iPSCs

    DEFF Research Database (Denmark)

    Mandegar, Mohammad A.; Huebsch, Nathaniel; Frolov, Ekaterina B.

    2016-01-01

    repression system is tunable and has the potential to silence single alleles. Compared with CRISPR nuclease (CRISPRn), CRISPRi gene repression is more efficient and homogenous across cell populations. The CRISPRi system in iPSCs provides a powerful platform to perform genome-scale screens in a wide range...

  15. Generation of iPSC from cardiac and tail-tip fibroblasts derived from a second heart field reporter mouse.

    Science.gov (United States)

    Linares, Javier; Arellano-Viera, Estibaliz; Iglesias-García, Olalla; Ferreira, Carmen; Iglesias, Elena; Abizanda, Gloria; Prósper, Felipe; Carvajal-Vergara, Xonia

    2016-05-01

    Mef2c Anterior Heart Field (AHF) enhancer is activated during embryonic heart development and it is expressed in multipotent cardiovascular progenitors (CVP) giving rise to endothelial and myocardial components of the outflow tract, right ventricle and ventricular septum. Here we have generated iPSC from transgenic Mef2c-AHF-Cre x Ai6(RCLZsGreen) mice. These iPSC will provide a novel tool to investigate the AHF-CVP and their cell progeny. Copyright © 2016 Roslin Cells Ltd. Published by Elsevier B.V. All rights reserved.

  16. Striking similarity in the gene expression levels of individual Myc module members among ESCs, EpiSCs, and partial iPSCs.

    Directory of Open Access Journals (Sweden)

    Masataka Hirasaki

    Full Text Available Predominant transcriptional subnetworks called Core, Myc, and PRC modules have been shown to participate in preservation of the pluripotency and self-renewality of embryonic stem cells (ESCs. Epiblast stem cells (EpiSCs are another cell type that possesses pluripotency and self-renewality. However, the roles of these modules in EpiSCs have not been systematically examined to date. Here, we compared the average expression levels of Core, Myc, and PRC module genes between ESCs and EpiSCs. EpiSCs showed substantially higher and lower expression levels of PRC and Core module genes, respectively, compared with those in ESCs, while Myc module members showed almost equivalent levels of average gene expression. Subsequent analyses revealed that the similarity in gene expression levels of the Myc module between these two cell types was not just overall, but striking similarities were evident even when comparing the expression of individual genes. We also observed equivalent levels of similarity in the expression of individual Myc module genes between induced pluripotent stem cells (iPSCs and partial iPSCs that are an unwanted byproduct generated during iPSC induction. Moreover, our data demonstrate that partial iPSCs depend on a high level of c-Myc expression for their self-renewal properties.

  17. Transient acquisition of pluripotency during somatic cell transdifferentiation with iPSC reprogramming factors.

    Science.gov (United States)

    Maza, Itay; Caspi, Inbal; Zviran, Asaf; Chomsky, Elad; Rais, Yoach; Viukov, Sergey; Geula, Shay; Buenrostro, Jason D; Weinberger, Leehee; Krupalnik, Vladislav; Hanna, Suhair; Zerbib, Mirie; Dutton, James R; Greenleaf, William J; Massarwa, Rada; Novershtern, Noa; Hanna, Jacob H

    2015-07-01

    Somatic cells can be transdifferentiated to other cell types without passing through a pluripotent state by ectopic expression of appropriate transcription factors. Recent reports have proposed an alternative transdifferentiation method in which fibroblasts are directly converted to various mature somatic cell types by brief expression of the induced pluripotent stem cell (iPSC) reprogramming factors Oct4, Sox2, Klf4 and c-Myc (OSKM) followed by cell expansion in media that promote lineage differentiation. Here we test this method using genetic lineage tracing for expression of endogenous Nanog and Oct4 and for X chromosome reactivation, as these events mark acquisition of pluripotency. We show that the vast majority of reprogrammed cardiomyocytes or neural stem cells obtained from mouse fibroblasts by OSKM-induced 'transdifferentiation' pass through a transient pluripotent state, and that their derivation is molecularly coupled to iPSC formation mechanisms. Our findings underscore the importance of defining trajectories during cell reprogramming by various methods.

  18. Demyelinating polyneuropathy with focally folded myelin sheaths in a family of Miniature Schnauzer dogs.

    Science.gov (United States)

    Vanhaesebrouck, An E; Couturier, Jérôme; Cauzinille, Laurent; Mizisin, Andrew P; Shelton, G Diane; Granger, Nicolas

    2008-12-15

    A spontaneous demyelinating polyneuropathy in two young Miniature Schnauzer dogs was characterized clinically, electrophysiologically and histopathologically. Both dogs were related and a third dog, belonging to the same family, had similar clinical signs. On presentation, clinical signs were restricted to respiratory dysfunction. Electrophysiological tests showed a dramatic decrease in both motor and sensory nerve conduction velocities. Microscopic examination of peripheral nerve biopsies (light and electron microscopy, teased nerve fibers), showed that this neuropathy was characterized by segmental demyelination and focally folded myelin sheaths. Various clinical syndromes associated with tomacula or focal thickening of the myelin sheath of the peripheral nerves have been described in humans and shown to be caused by gene mutations affecting the myelin proteins, such as the hereditary neuropathy with liability to pressure palsies or the demyelinating forms of Charcot-Marie-Tooth disease. In animals, a tomaculous neuropathy has been reported in cattle and chickens but not in carnivores. Here we report a demyelinating peripheral neuropathy with tomacula in two Miniature Schnauzer dogs.

  19. Generation, genome edition and characterization of iPSC lines from a patient with coenzyme Q10 deficiency harboring a heterozygous mutation in COQ4 gene

    Directory of Open Access Journals (Sweden)

    Damià Romero-Moya

    2017-10-01

    Full Text Available We report the generation, CRISPR/Cas9-edition and characterization of induced pluripotent stem cell (iPSC lines from a patient with coenzyme Q10 deficiency harboring the heterozygous mutation c.483G > C in the COQ4 gene. iPSCs were generated using non-integrative Sendai Viruses containing the reprogramming factors OCT4, SOX2, KLF4 and C-MYC. The iPSC lines carried the c.483G > C COQ4 mutation, silenced the OKSM expression and were mycoplasma-free. They were bona fide pluripotent cells as characterized by morphology, immunophenotype/gene expression for pluripotent-associated markers/genes, NANOG and OCT4 promoter demethylation, karyotype and teratoma formation. The COQ4 mutation was CRISPR/Cas9 edited resulting in isogenic, diploid and off-target free COQ4-corrected iPSCs.

  20. Introduction to thematic minireview series: Development of human therapeutics based on induced pluripotent stem cell (iPSC) technology.

    Science.gov (United States)

    Rao, Mahendra; Gottesfeld, Joel M

    2014-02-21

    With the advent of human induced pluripotent stem cell (hiPSC) technology, it is now possible to derive patient-specific cell lines that are of great potential in both basic research and the development of new therapeutics for human diseases. Not only do hiPSCs offer unprecedented opportunities to study cellular differentiation and model human diseases, but the differentiated cell types obtained from iPSCs may become therapeutics themselves. These cells can also be used in the screening of therapeutics and in toxicology assays for potential liabilities of therapeutic agents. The remarkable achievement of transcription factor reprogramming to generate iPSCs was recognized by the award of the Nobel Prize in Medicine to Shinya Yamanaka in 2012, just 6 years after the first publication of reprogramming methods to generate hiPSCs (Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., and Yamanaka, S. (2007) Cell 131, 861-872). This minireview series highlights both the promises and challenges of using iPSC technology for disease modeling, drug screening, and the development of stem cell therapeutics.

  1. The Whole new world of miniature technology

    Energy Technology Data Exchange (ETDEWEB)

    Gillespie, L.K.

    1980-07-01

    In the past ten years, miniaturization of both electrical and mechanical parts has significantly increased. Documentation of the design and production capabilities of miniaturization in the electronics industry is well-defined. Literature on the subject of miniaturization of metal piece parts, however, is hard to find. Some of the current capabilities in the manufacture of miniature metal piece parts or miniature features in larger piece parts are discussed.

  2. Using CRISPR-Cas9 to Generate Gene-Corrected Autologous iPSCs for the Treatment of Inherited Retinal Degeneration.

    Science.gov (United States)

    Burnight, Erin R; Gupta, Manav; Wiley, Luke A; Anfinson, Kristin R; Tran, Audrey; Triboulet, Robinson; Hoffmann, Jeremy M; Klaahsen, Darcey L; Andorf, Jeaneen L; Jiao, Chunhua; Sohn, Elliott H; Adur, Malavika K; Ross, Jason W; Mullins, Robert F; Daley, George Q; Schlaeger, Thorsten M; Stone, Edwin M; Tucker, Budd A

    2017-09-06

    Patient-derived induced pluripotent stem cells (iPSCs) hold great promise for autologous cell replacement. However, for many inherited diseases, treatment will likely require genetic repair pre-transplantation. Genome editing technologies are useful for this application. The purpose of this study was to develop CRISPR-Cas9-mediated genome editing strategies to target and correct the three most common types of disease-causing variants in patient-derived iPSCs: (1) exonic, (2) deep intronic, and (3) dominant gain of function. We developed a homology-directed repair strategy targeting a homozygous Alu insertion in exon 9 of male germ cell-associated kinase (MAK) and demonstrated restoration of the retinal transcript and protein in patient cells. We generated a CRISPR-Cas9-mediated non-homologous end joining (NHEJ) approach to excise a major contributor to Leber congenital amaurosis, the IVS26 cryptic-splice mutation in CEP290, and demonstrated correction of the transcript and protein in patient iPSCs. Lastly, we designed allele-specific CRISPR guides that selectively target the mutant Pro23His rhodopsin (RHO) allele, which, following delivery to both patient iPSCs in vitro and pig retina in vivo, created a frameshift and premature stop that would prevent transcription of the disease-causing variant. The strategies developed in this study will prove useful for correcting a wide range of genetic variants in genes that cause inherited retinal degeneration. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  3. Myeloid leukemias and virally induced lymphomas in miniature inbred swine; development of a large animal tumor model

    Directory of Open Access Journals (Sweden)

    RAIMON eDURAN-STRUUCK

    2015-11-01

    Full Text Available The lack of a large animal transplantable tumor model has limited the study of novel therapeutic strategies for the treatment of liquid cancers. Swine as a species provide a natural option based on their similarities with humans and their already extensive use in biomedical research. Specifically, the MGH miniature swine herd retains unique genetic characteristics that facilitate the study of hematopoietic cell and solid organ transplantation. Spontaneously arising liquid cancers in these swine, specifically myeloid leukemias and B cell lymphomas, closely resemble human malignancies. The ability to establish aggressive tumor cell lines in vitro from these naturally occurring malignancies makes a transplantable tumor model a close reality. Here, we discuss our experience with myeloid and lymphoid tumors in MHC characterized miniature swine and future approaches regarding the development of a large animal transplantable tumor model.

  4. Miniature Optical Isolator, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — To address NASA's need for miniature optical isolators in atom interferometry applications, Physical Optics Corporation (POC) proposes to develop a miniature optical...

  5. Reversible dual inhibitor against G9a and DNMT1 improves human iPSC derivation enhancing MET and facilitating transcription factor engagement to the genome.

    Directory of Open Access Journals (Sweden)

    Juan Roberto Rodriguez-Madoz

    Full Text Available The combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of iPSCs and could be used for disease modelling, high throughput screenings and/or regenerative medicine applications. In this study, we showed that a new first-in-class reversible dual G9a/DNMT1 inhibitor compound (CM272 improves the efficiency of human cell reprogramming and iPSC generation from primary cells of healthy donors and patient samples, using both integrative and non-integrative methods. Moreover, CM272 facilitates the generation of human iPSC with only two factors allowing the removal of the most potent oncogenic factor cMYC. Furthermore, we demonstrated that mechanistically, treatment with CM272 induces heterochromatin relaxation, facilitates the engagement of OCT4 and SOX2 transcription factors to OSKM refractory binding regions that are required for iPSC establishment, and enhances mesenchymal to epithelial transition during the early phase of cell reprogramming. Thus, the use of this new G9a/DNMT reversible dual inhibitor compound may represent an interesting alternative for improving cell reprogramming and human iPSC derivation for many different applications while providing interesting insights into reprogramming mechanisms.

  6. Reversible dual inhibitor against G9a and DNMT1 improves human iPSC derivation enhancing MET and facilitating transcription factor engagement to the genome.

    Science.gov (United States)

    Rodriguez-Madoz, Juan Roberto; San Jose-Eneriz, Edurne; Rabal, Obdulia; Zapata-Linares, Natalia; Miranda, Estibaliz; Rodriguez, Saray; Porciuncula, Angelo; Vilas-Zornoza, Amaia; Garate, Leire; Segura, Victor; Guruceaga, Elizabeth; Agirre, Xabier; Oyarzabal, Julen; Prosper, Felipe

    2017-01-01

    The combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of iPSCs and could be used for disease modelling, high throughput screenings and/or regenerative medicine applications. In this study, we showed that a new first-in-class reversible dual G9a/DNMT1 inhibitor compound (CM272) improves the efficiency of human cell reprogramming and iPSC generation from primary cells of healthy donors and patient samples, using both integrative and non-integrative methods. Moreover, CM272 facilitates the generation of human iPSC with only two factors allowing the removal of the most potent oncogenic factor cMYC. Furthermore, we demonstrated that mechanistically, treatment with CM272 induces heterochromatin relaxation, facilitates the engagement of OCT4 and SOX2 transcription factors to OSKM refractory binding regions that are required for iPSC establishment, and enhances mesenchymal to epithelial transition during the early phase of cell reprogramming. Thus, the use of this new G9a/DNMT reversible dual inhibitor compound may represent an interesting alternative for improving cell reprogramming and human iPSC derivation for many different applications while providing interesting insights into reprogramming mechanisms.

  7. A Comparative View on Human Somatic Cell Sources for iPSC Generation

    Directory of Open Access Journals (Sweden)

    Stefanie Raab

    2014-01-01

    Full Text Available The breakthrough of reprogramming human somatic cells was achieved in 2006 by the work of Yamanaka and Takahashi. From this point, fibroblasts are the most commonly used primary somatic cell type for the generation of induced pluripotent stem cells (iPSCs. Various characteristics of fibroblasts supported their utilization for the groundbreaking experiments of iPSC generation. One major advantage is the high availability of fibroblasts which can be easily isolated from skin biopsies. Furthermore, their cultivation, propagation, and cryoconservation properties are uncomplicated with respect to nutritional requirements and viability in culture. However, the required skin biopsy remains an invasive approach, representing a major drawback for using fibroblasts as the starting material. More and more studies appeared over the last years, describing the reprogramming of other human somatic cell types. Cells isolated from blood samples or urine, as well as more unexpected cell types, like pancreatic islet beta cells, synovial cells, or mesenchymal stromal cells from wisdom teeth, show promising characteristics for a reprogramming strategy. Here, we want to highlight the advantages of keratinocytes from human plucked hair as a widely usable, noninvasive harvesting method for primary material in comparison with other commonly used cell types.

  8. Dr.Johnson's Dictionary in Miniature

    OpenAIRE

    Imazato, Chiaki

    1988-01-01

    More than hundred 'Johnson's' dictionaries have so far been published not only in English but in other countries, and there are numerous books and articles on Johnson's Dictionary. But few have referred to Johnson's Dictionary in Miniature; nor were there any books or articles on it. Fortunately, however, I've got one copy of Johnson's Dictionary in Miniature, which was published in 1806. Johnson's Dictionary (1755) has 41,677 entries, whereas Johnson's Dictionary in Miniature 23,439 entr...

  9. The miniature accelerator

    CERN Multimedia

    Antonella Del Rosso

    2015-01-01

    The image that most people have of CERN is of its enormous accelerators and their capacity to accelerate particles to extremely high energies. But thanks to some cutting-edge studies on beam dynamics and radiofrequency technology, along with innovative construction techniques, teams at CERN have now created the first module of a brand-new accelerator, which will be just 2 metres long. The potential uses of this miniature accelerator will include deployment in hospitals for the production of medical isotopes and the treatment of cancer. It’s a real David-and-Goliath story.   Serge Mathot, in charge of the construction of the "mini-RFQ", pictured with the first of the four modules that will make up the miniature accelerator. The miniature accelerator consists of a radiofrequency quadrupole (RFQ), a component found at the start of all proton accelerator chains around the world, from the smallest to the largest. The LHC is designed to produce very high-intensity beams ...

  10. Strange Animals and Creatures in Islamic Miniatures: Focusing on Miniatures of the Conference of the Birds

    Directory of Open Access Journals (Sweden)

    Neda Rohani

    2017-09-01

    Full Text Available Strange animals and creatures have always existed in every mythological culture. In Iran's pre-Islamic and post-Islamic miniatures and reliefs, there are many strange animals and creatures such as dragons and phoenix which were associated with the Iranian culture and civilization. Because of presence of these strange creatures, particularly human life, these creatures are first used in mythological life and then symbolically to express human ideas. However, these animals were present in both mythology and epics and, later in the Islamic era, in the mystical stories, educational stories and admonishing anecdotes like Sanai, Attar, and Rumi. This study tends to investigate genealogy of strange animals and creatures in ancient Iranian reliefs and their continued presence in miniatures of Islamic era as well as presence of these creatures in miniatures which are based on Attar’s Conference of the Birds. In fact, this study reviews elements and symbolic concepts of animals, allowing a deeper understanding of function of elements and symbolism in works of Iranian miniaturists. Contemplation of miniatures, icons and the relationship between literature and miniatures will lead to many results in recognition of mystical intellectual foundations. Therefore, this study tends to investigate mysterious and unknown aspects of Iranian miniatures and find their relationship with culture and stories.

  11. Regenerative therapy for vestibular disorders using human induced pluripotent stem cells (iPSCs): neural differentiation of human iPSC-derived neural stem cells after in vitro transplantation into mouse vestibular epithelia.

    Science.gov (United States)

    Taura, Akiko; Nakashima, Noriyuki; Ohnishi, Hiroe; Nakagawa, Takayuki; Funabiki, Kazuo; Ito, Juichi; Omori, Koichi

    2016-10-01

    Vestibular ganglion cells, which convey sense of motion from vestibular hair cells to the brainstem, are known to degenerate with aging and after vestibular neuritis. Thus, regeneration of vestibular ganglion cells is important to aid in the recovery of balance for associated disorders. The present study derived hNSCs from induced pluripotent stem cells (iPSCs) and transplanted these cells into mouse utricle tissues. After a 7-day co-culture period, histological and electrophysiological examinations of transplanted hNSCs were performed. Injected hNSC-derived cells produced elongated axon-like structures within the utricle tissue that made contact with vestibular hair cells. A proportion of hNSC-derived cells showed spontaneous firing activities, similar to those observed in cultured mouse vestibular ganglion cells. However, hNSC-derived cells around the mouse utricle persisted as immature neurons or occasionally differentiated into putative astrocytes. Moreover, electrophysiological examination showed hNSC-derived cells around utricles did not exhibit any obvious spontaneous firing activities. Injected human neural stem cells (hNSCs) showed signs of morphological maturation including reconnection to denervated hair cells and partial physiological maturation, suggesting hNSC-derived cells possibly differentiated into neurons.

  12. Visual thread quality for precision miniature mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Gillespie, L.K.

    1981-04-01

    Threaded features have eight visual appearance factors which can affect their function in precision miniature mechanisms. The Bendix practice in deburring, finishing, and accepting these conditions on miniature threads is described as is their impact in assemblies of precision miniature electromechanical assemblies.

  13. Aberrant DNA Methylation in Human iPSCs Associates with MYC-Binding Motifs in a Clone-Specific Manner Independent of Genetics.

    Science.gov (United States)

    Panopoulos, Athanasia D; Smith, Erin N; Arias, Angelo D; Shepard, Peter J; Hishida, Yuriko; Modesto, Veronica; Diffenderfer, Kenneth E; Conner, Clay; Biggs, William; Sandoval, Efren; D'Antonio-Chronowska, Agnieszka; Berggren, W Travis; Izpisua Belmonte, Juan Carlos; Frazer, Kelly A

    2017-04-06

    Induced pluripotent stem cells (iPSCs) show variable methylation patterns between lines, some of which reflect aberrant differences relative to embryonic stem cells (ESCs). To examine whether this aberrant methylation results from genetic variation or non-genetic mechanisms, we generated human iPSCs from monozygotic twins to investigate how genetic background, clone, and passage number contribute. We found that aberrantly methylated CpGs are enriched in regulatory regions associated with MYC protein motifs and affect gene expression. We classified differentially methylated CpGs as being associated with genetic and/or non-genetic factors (clone and passage), and we found that aberrant methylation preferentially occurs at CpGs associated with clone-specific effects. We further found that clone-specific effects play a strong role in recurrent aberrant methylation at specific CpG sites across different studies. Our results argue that a non-genetic biological mechanism underlies aberrant methylation in iPSCs and that it is likely based on a probabilistic process involving MYC that takes place during or shortly after reprogramming. Published by Elsevier Inc.

  14. Advances in Miniaturized Instruments for Genomics

    Directory of Open Access Journals (Sweden)

    Cihun-Siyong Alex Gong

    2014-01-01

    Full Text Available In recent years, a lot of demonstrations of the miniaturized instruments were reported for genomic applications. They provided the advantages of miniaturization, automation, sensitivity, and specificity for the development of point-of-care diagnostics. The aim of this paper is to report on recent developments on miniaturized instruments for genomic applications. Based on the mature development of microfabrication, microfluidic systems have been demonstrated for various genomic detections. Since one of the objectives of miniaturized instruments is for the development of point-of-care device, impedimetric detection is found to be a promising technique for this purpose. An in-depth discussion of the impedimetric circuits and systems will be included to provide total consideration of the miniaturized instruments and their potential application towards real-time portable imaging in the “-omics” era. The current excellent demonstrations suggest a solid foundation for the development of practical and widespread point-of-care genomic diagnostic devices.

  15. Nuclear Energy Advanced Modeling and Simulation Waste Integrated Performance and Safety Codes (NEAMS Waste IPSC) verification and validation plan. version 1.

    Energy Technology Data Exchange (ETDEWEB)

    Bartlett, Roscoe Ainsworth; Arguello, Jose Guadalupe, Jr.; Urbina, Angel; Bouchard, Julie F.; Edwards, Harold Carter; Freeze, Geoffrey A.; Knupp, Patrick Michael; Wang, Yifeng; Schultz, Peter Andrew; Howard, Robert (Oak Ridge National Laboratory, Oak Ridge, TN); McCornack, Marjorie Turner

    2011-01-01

    The objective of the U.S. Department of Energy Office of Nuclear Energy Advanced Modeling and Simulation Waste Integrated Performance and Safety Codes (NEAMS Waste IPSC) is to provide an integrated suite of computational modeling and simulation (M&S) capabilities to quantitatively assess the long-term performance of waste forms in the engineered and geologic environments of a radioactive-waste storage facility or disposal repository. To meet this objective, NEAMS Waste IPSC M&S capabilities will be applied to challenging spatial domains, temporal domains, multiphysics couplings, and multiscale couplings. A strategic verification and validation (V&V) goal is to establish evidence-based metrics for the level of confidence in M&S codes and capabilities. Because it is economically impractical to apply the maximum V&V rigor to each and every M&S capability, M&S capabilities will be ranked for their impact on the performance assessments of various components of the repository systems. Those M&S capabilities with greater impact will require a greater level of confidence and a correspondingly greater investment in V&V. This report includes five major components: (1) a background summary of the NEAMS Waste IPSC to emphasize M&S challenges; (2) the conceptual foundation for verification, validation, and confidence assessment of NEAMS Waste IPSC M&S capabilities; (3) specifications for the planned verification, validation, and confidence-assessment practices; (4) specifications for the planned evidence information management system; and (5) a path forward for the incremental implementation of this V&V plan.

  16. Monte Carlo method implementation on IPSC 860 for the resolution of the Boltzmann equation

    International Nuclear Information System (INIS)

    AloUGES, Francois

    1993-01-01

    This note deals with the implementation on a massively parallel machine (IPSC-860) of a Monte-Carlo method aiming at resolving the Boltzmann equation. The parallelism of the machine incites to consider a multi-domain approach and poses the problem of the automatic generation of local meshes from a non-structured 3-D global mesh [fr

  17. Generation of induced pluripotent stem cells (iPSCs) stably expressing CRISPR-based synergistic activation mediator (SAM).

    Science.gov (United States)

    Xiong, Kai; Zhou, Yan; Hyttel, Poul; Bolund, Lars; Freude, Kristine Karla; Luo, Yonglun

    2016-11-01

    Human fibroblasts were engineered to express the CRISPR-based synergistic activation mediator (SAM) complex: dCas9-VP64 and MS2-P65-HSF1. Two induced pluripotent stem cells (iPSCs) clones expressing SAM were established by transducing these fibroblasts with lentivirus expressing OCT4, SOX2, KLF4 and C-MYC. We have validated that the reprogramming cassette is silenced in the SAM iPSC clones. Expression of pluripotency genes (OCT4, SOX2, LIN28A, NANOG, GDF3, SSEA4, and TRA-1-60), differentiation potential to all three germ layers, and normal karyotypes are validated. These SAM-iPSCs provide a novel, useful tool to investigate genetic regulation of stem cell proliferation and differentiation through CRISPR-mediated activation of endogenous genes. Copyright © 2016 Michael Boutros, German Cancer Research Center, Heidelberg, Germany. Published by Elsevier B.V. All rights reserved.

  18. EZ spheres: a stable and expandable culture system for the generation of pre-rosette multipotent stem cells from human ESCs and iPSCs

    OpenAIRE

    Ebert, A.; Shelley, B.; Hurley, A.; Onorati, M.; Castiglioni, V.; Patitucci, T.; Svendsen, S.; Mattis, V.; Mcgivern, J.; Schwab, A.; Sareen, D.; Kim, H.; Cattaneo, E.; Svendsen, C.

    2013-01-01

    We have developed a simple method to generate and expand multipotent, self-renewing pre-rosette neural stem cells from both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs) without utilizing embryoid body formation, manual selection techniques, or complex combinations of small molecules. Human ESC and iPSC colonies were lifted and placed in a neural stem cell medium containing high concentrations of EGF and FGF-2. Cell aggregates (termed EZ spheres) could be...

  19. Cerebellar abiotrophy in a miniature schnauzer

    OpenAIRE

    Berry, Michelle L.; Blas-Machado, Uriel

    2003-01-01

    A 3.5-month-old miniature schnauzer was presented for signs of progressive cerebellar ataxia. Necropsy revealed cerebellar abiotrophy. This is the first reported case of cerebellar abiotrophy in a purebred miniature schnauzer.

  20. Cerebellar abiotrophy in a miniature schnauzer.

    Science.gov (United States)

    Berry, Michelle L; Blas-Machado, Uriel

    2003-08-01

    A 3.5-month-old miniature schnauzer was presented for signs of progressive cerebellar ataxia. Necropsy revealed cerebellar abiotrophy. This is the first reported case of cerebellar abiotrophy in a purebred miniature schnauzer.

  1. Decreased neural precursor cell pool in NADPH oxidase 2-deficiency: From mouse brain to neural differentiation of patient derived iPSC

    Directory of Open Access Journals (Sweden)

    Zeynab Nayernia

    2017-10-01

    Full Text Available There is emerging evidence for the involvement of reactive oxygen species (ROS in the regulation of stem cells and cellular differentiation. Absence of the ROS-generating NADPH oxidase NOX2 in chronic granulomatous disease (CGD patients, predominantly manifests as immune deficiency, but has also been associated with decreased cognition. Here, we investigate the role of NOX enzymes in neuronal homeostasis in adult mouse brain and in neural cells derived from human induced pluripotent stem cells (iPSC. High levels of NOX2 were found in mouse adult neurogenic regions. In NOX2-deficient mice, neurogenic regions showed diminished redox modifications, as well as decrease in neuroprecursor numbers and in expression of genes involved in neural differentiation including NES, BDNF and OTX2. iPSC from healthy subjects and patients with CGD were used to study the role of NOX2 in human in vitro neuronal development. Expression of NOX2 was low in undifferentiated iPSC, upregulated upon neural induction, and disappeared during neuronal differentiation. In human neurospheres, NOX2 protein and ROS generation were polarized within the inner cell layer of rosette structures. NOX2 deficiency in CGD-iPSCs resulted in an abnormal neural induction in vitro, as revealed by a reduced expression of neuroprogenitor markers (NES, BDNF, OTX2, NRSF/REST, and a decreased generation of mature neurons. Vector-mediated NOX2 expression in NOX2-deficient iPSCs rescued neurogenesis. Taken together, our study provides novel evidence for a regulatory role of NOX2 during early stages of neurogenesis in mouse and human.

  2. Both TALENs and CRISPR/Cas9 directly target the HBB IVS2-654 (C > T) mutation in β-thalassemia-derived iPSCs.

    Science.gov (United States)

    Xu, Peng; Tong, Ying; Liu, Xiu-zhen; Wang, Ting-ting; Cheng, Li; Wang, Bo-yu; Lv, Xiang; Huang, Yue; Liu, De-pei

    2015-07-09

    β-Thalassemia is one of the most common genetic blood diseases and is caused by either point mutations or deletions in the β-globin (HBB) gene. The generation of patient-specific induced pluripotent stem cells (iPSCs) and subsequent correction of the disease-causing mutations may be a potential therapeutic strategy for this disease. Due to the low efficiency of typical homologous recombination, endonucleases, including TALENs and CRISPR/Cas9, have been widely used to enhance the gene correction efficiency in patient-derived iPSCs. Here, we designed TALENs and CRISPR/Cas9 to directly target the intron2 mutation site IVS2-654 in the globin gene. We observed different frequencies of double-strand breaks (DSBs) at IVS2-654 loci using TALENs and CRISPR/Cas9, and TALENs mediated a higher homologous gene targeting efficiency compared to CRISPR/Cas9 when combined with the piggyBac transposon donor. In addition, more obvious off-target events were observed for CRISPR/Cas9 compared to TALENs. Finally, TALENs-corrected iPSC clones were selected for erythroblast differentiation using the OP9 co-culture system and detected relatively higher transcription of HBB than the uncorrected cells. This comparison of using TALENs or CRISPR/Cas9 to correct specific HBB mutations in patient-derived iPSCs will guide future applications of TALENs- or CRISPR/Cas9-based gene therapies in monogenic diseases.

  3. Generation of iPSC line epiHUVEC from human umbilical vein endothelial cells

    Directory of Open Access Journals (Sweden)

    Peggy Matz

    2015-11-01

    Full Text Available Human umbilical vein endothelial cells (HUVECs were used to generate the iPSC line epiHUVEC employing a combination of three episomal-based plasmids expressing OCT4, SOX2, NANOG, LIN28, c-MYC and KLF4. Pluripotency was confirmed both in vivo and in vitro. The transcriptome profile of epiHUVEC and the human embryonic stem cell line — H1 have a Pearson correlation of 0.899.

  4. Inheritance of congenital cataracts and microphthalmia in the Miniature Schnauzer.

    Science.gov (United States)

    Gelatt, K N; Samuelson, D A; Bauer, J E; Das, N D; Wolf, E D; Barrie, K P; Andresen, T L

    1983-06-01

    Congenital cataracts and microphthalmia in the Miniature Schnauzer were inherited as an autosomal recessive trait. Eighteen matings of affected X affected Miniature Schnauzers resulted in 87 offspring with congenital cataracts and microphthalmia (49 males/38 females). Two matings of congenital cataractous and microphthalmic Miniature Schnauzers (2 females) X a normal Miniature Schnauzer (1 male) yielded 11 clinically normal Miniature Schnauzers (7 males/4 females). Eighteen matings of congenital cataractous and microphthalmic Miniature Schnauzers (6 males) X carrier Miniature Schnauzers (9 females) produced 81 offspring; 39 exhibited congenital cataracts and microphthalmia (20 males/19 females) and 42 had clinically normal eyes (17 males/25 females).

  5. Serum C-reactive protein concentrations in healthy Miniature Schnauzer dogs.

    Science.gov (United States)

    Wong, Valerie M; Kidney, Beverly A; Snead, Elisabeth C R; Myers, Sherry L; Jackson, Marion L

    2011-09-01

    C-reactive protein (CRP) is a sensitive marker for inflammation in people and dogs. In people, an association between CRP concentration and atherosclerosis has been reported. Atherosclerosis is rare in dogs, but the Miniature Schnauzer breed may be at increased risk for developing this vascular disease. It is not known if CRP concentrations in Miniature Schnauzer dogs differ from those in other dog breeds. Our objectives were to validate an automated human CRP assay for measuring CRP in dogs and compare CRP concentrations in healthy Miniature Schnauzer dogs with those in non-Miniature Schnauzer breeds. Sera from 37 non-Miniature Schnauzer dogs with inflammatory disease were pooled and used to validate a human CRP immunoturbidimetric assay for measuring canine CRP. Blood was collected from 20 healthy Miniature Schnauzer dogs and 41 healthy dogs of other breeds. Median serum CRP concentration of healthy Miniature Schnauzer dogs was compared with that of healthy non-Miniature Schnauzer dogs. The human CRP assay measured CRP reliably with linearity between 0 and 20 mg/L. CRP concentration for healthy Miniature Schnauzer dogs (median 4.0 mg/L, minimum-maximum 0-18.2 mg/L) was significantly higher than for the healthy non-Miniature Schnauzer dogs (median 0.1 mg/L, minimum-maximum 0-10.7 mg/L); 17 of the 20 Miniature Schnauzer dogs had values that overlapped with those of the non-Miniature Schnauzer dogs. Median CRP concentration of Miniature Schnauzer dogs was slightly higher than that of other breeds of dogs. A relationship between higher CRP concentration in Miniature Schnauzer dogs and idiopathic hyperlipidemia, pancreatitis, and possible increased risk for atherosclerosis remains to be determined. ©2011 American Society for Veterinary Clinical Pathology.

  6. The Combination of CRISPR/Cas9 and iPSC Technologies in the Gene Therapy of Human β-thalassemia in Mice.

    Science.gov (United States)

    Ou, Zhanhui; Niu, Xiaohua; He, Wenyin; Chen, Yuchang; Song, Bing; Xian, Yexing; Fan, Di; Tang, Daolin; Sun, Xiaofang

    2016-09-01

    β-thalassemia results from point mutations or small deletions in the β-globin (HBB) gene that ultimately cause anemia. The generation of induced pluripotent stem cells (iPSCs) from the somatic cells of patients in combination with subsequent homologous recombination-based gene correction provides new approaches to cure this disease. CRISPR/Cas9 is a genome editing tool that is creating a buzz in the scientific community for treating human diseases, especially genetic disorders. Here, we reported that correction of β-thalassemia mutations in patient-specific iPSCs using the CRISPR/Cas9 tool promotes hematopoietic differentiation in vivo. CRISPR/Cas9-corrected iPSC-derived hematopoietic stem cells (HSCs) were injected into sublethally-irradiated NOD-scid-IL2Rg-/- (NSI) mice. HBB expression was observed in these HSCs after hematopoietic differentiation in the NSI mice. Importantly, no tumor was found in the livers, lungs, kidneys, or bone marrow at 10 weeks in the NSI mice after implantation with these HSCs. Collectively, our findings demonstrated that CRISPR/Cas9 successfully corrects β-thalassemia mutations in patient-specific iPSCs. These CRISPR/Cas9-corrected iPSC-derived HSCs express normal HBB in mice without tumorigenic potential, suggesting a safe strategy for personalized treatment of β-thalassemia.

  7. Transient Acquisition of Pluripotency During Somatic Cell Transdifferentiation with iPSC Reprogramming Factors

    OpenAIRE

    Maza, Itay; Caspi, Inbal; Zviran, Asaf; Chomsky, Elad; Rais, Yoach; Viukov, Sergey; Geula, Shay; Buenrostro, Jason D.; Weinberger, Leehee; Krupalnik, Vladislav; Hanna, Suhair; Zerbib, Mirie; Dutton, James R.; Greenleaf, William J.; Massarwa, Rada

    2015-01-01

    Somatic cells can be transdifferentiated to other cell types without passing through a pluripotent state by ectopic expression of appropriate transcription factors 1,2 . Recent reports have proposed an alternative transdifferentiation method in which fibroblasts are directly converted to various mature somatic cell types by brief expression of the induced pluripotent stem cell (iPSC) reprogramming factors Oct4, Sox2, Klf4 and c-Myc (OSKM) followed by cell expansion in media that promote linea...

  8. Reestablishment of radiographic kidney size in Miniature Schnauzer dogs.

    Science.gov (United States)

    Sohn, Jungmin; Yun, Sookyung; Lee, Jeosoon; Chang, Dongwoo; Choi, Mincheol; Yoon, Junghee

    2017-01-10

    Kidney size may be altered in renal diseases, and the detection of kidney size alteration has diagnostic and prognostic values. We hypothesized that radiographic kidney size, the kidney length to the second lumbar vertebra (L2) length ratio, in normal Miniature Schnauzer dogs may be overestimated due to their shorter vertebral length. This study was conducted to evaluate radiographic and ultrasonographic kidney size and L2 length in clinically normal Miniature Schnauzers and other dog breeds to evaluate the effect of vertebral length on radiographic kidney size and to reestablish radiographic kidney size in normal Miniature Schnauzers. Abdominal radiographs and ultrasonograms from 49 Miniature Schnauzers and 54 other breeds without clinical evidence of renal disease and lumbar vertebral abnormality were retrospectively evaluated. Radiographic kidney size, in the Miniature Schnauzer (3.31 ± 0.26) was significantly larger than that in other breeds (2.94 ± 0.27). Relative L2 length, the L2 length to width ratio, in the Miniature Schnauzer (1.11 ± 0.06) was significantly shorter than that in other breeds (1.21 ± 0.09). However, ultrasonographic kidney sizes, kidney length to aorta diameter ratios, were within or very close to normal range both in the Miniature Schnauzer (6.75 ± 0.67) and other breeds (7.16 ± 1.01). Thus, Miniature Schnauzer dogs have breed-specific short vertebrae and consequently a larger radiographic kidney size, which was greater than standard reference in normal adult dogs. Care should be taken when evaluating radiographic kidney size in Miniature Schnauzers to prevent falsely diagnosed renomegaly.

  9. Small Scaffolds, Big Potential: Developing Miniature Proteins as Therapeutic Agents.

    Science.gov (United States)

    Holub, Justin M

    2017-09-01

    Preclinical Research Miniature proteins are a class of oligopeptide characterized by their short sequence lengths and ability to adopt well-folded, three-dimensional structures. Because of their biomimetic nature and synthetic tractability, miniature proteins have been used to study a range of biochemical processes including fast protein folding, signal transduction, catalysis and molecular transport. Recently, miniature proteins have been gaining traction as potential therapeutic agents because their small size and ability to fold into defined tertiary structures facilitates their development as protein-based drugs. This research overview discusses emerging developments involving the use of miniature proteins as scaffolds to design novel therapeutics for the treatment and study of human disease. Specifically, this review will explore strategies to: (i) stabilize miniature protein tertiary structure; (ii) optimize biomolecular recognition by grafting functional epitopes onto miniature protein scaffolds; and (iii) enhance cytosolic delivery of miniature proteins through the use of cationic motifs that facilitate endosomal escape. These objectives are discussed not only to address challenges in developing effective miniature protein-based drugs, but also to highlight the tremendous potential miniature proteins hold for combating and understanding human disease. Drug Dev Res 78 : 268-282, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  10. Miniaturized isothermal nucleic acid amplification, a review.

    Science.gov (United States)

    Asiello, Peter J; Baeumner, Antje J

    2011-04-21

    Micro-Total Analysis Systems (µTAS) for use in on-site rapid detection of DNA or RNA are increasingly being developed. Here, amplification of the target sequence is key to increasing sensitivity, enabling single-cell and few-copy nucleic acid detection. The several advantages to miniaturizing amplification reactions and coupling them with sample preparation and detection on the same chip are well known and include fewer manual steps, preventing contamination, and significantly reducing the volume of expensive reagents. To-date, the majority of miniaturized systems for nucleic acid analysis have used the polymerase chain reaction (PCR) for amplification and those systems are covered in previous reviews. This review provides a thorough overview of miniaturized analysis systems using alternatives to PCR, specifically isothermal amplification reactions. With no need for thermal cycling, isothermal microsystems can be designed to be simple and low-energy consuming and therefore may outperform PCR in portable, battery-operated detection systems in the future. The main isothermal methods as miniaturized systems reviewed here include nucleic acid sequence-based amplification (NASBA), loop-mediated isothermal amplification (LAMP), helicase-dependent amplification (HDA), rolling circle amplification (RCA), and strand displacement amplification (SDA). Also, important design criteria for the miniaturized devices are discussed. Finally, the potential of miniaturization of some new isothermal methods such as the exponential amplification reaction (EXPAR), isothermal and chimeric primer-initiated amplification of nucleic acids (ICANs), signal-mediated amplification of RNA technology (SMART) and others is presented.

  11. Miniaturization in Biocatalysis

    Directory of Open Access Journals (Sweden)

    Pedro Fernandes

    2010-03-01

    Full Text Available The use of biocatalysts for the production of both consumer goods and building blocks for chemical synthesis is consistently gaining relevance. A significant contribution for recent advances towards further implementation of enzymes and whole cells is related to the developments in miniature reactor technology and insights into flow behavior. Due to the high level of parallelization and reduced requirements of chemicals, intensive screening of biocatalysts and process variables has become more feasible and reproducibility of the bioconversion processes has been substantially improved. The present work aims to provide an overview of the applications of miniaturized reactors in bioconversion processes, considering multi-well plates and microfluidic devices, update information on the engineering characterization of the hardware used, and present perspective developments in this area of research.

  12. Liquid storage of miniature boar semen.

    Science.gov (United States)

    Shimatsu, Yoshiki; Uchida, Masaki; Niki, Rikio; Imai, Hiroshi

    2002-04-01

    The effects of liquid storage at 15 degrees C on the fertilizing ability of miniature pig semen were investigated. Characterization of ejaculated semen from 3 miniature boars was carried out. Semen volume and pH were similar among these boars. In one of the boars, sperm motility was slightly low, and sperm concentration and total number of sperm were significantly lower than in the others (P semen was substituted with various extenders (Kiev, Androhep, BTS and Modena) by centrifugation and semen was stored for 7 days at 15 degrees C. Sperm motility was estimated daily at 37 degrees C. For complete substitution of seminal plasma, Modena was significantly more efficient than the other extenders (P Semen from each of the 3 miniature boars that had been stored for 5 to 7 days at 15 degrees C in Modena was used for artificial insemination of 15 miniature sows. The farrowing rates were 100, 100 and 60%, and litter sizes were 6.4 +/- 1.5, 5.8 +/- 0.8 and 5.0 +/- 1.0 for each boar semen, respectively. The boar that sired the smallest farrowing rate was the same one that showed lower seminal quality with respect to sperm motility, sperm concentration and total number of sperm. These results suggest that miniature boar semen can be stored for at least 5 days at 15 degrees C by the substitution of seminal plasma with Modena extender.

  13. Advances in miniature spectrometer and sensor development

    Science.gov (United States)

    Malinen, Jouko; Rissanen, Anna; Saari, Heikki; Karioja, Pentti; Karppinen, Mikko; Aalto, Timo; Tukkiniemi, Kari

    2014-05-01

    Miniaturization and cost reduction of spectrometer and sensor technologies has great potential to open up new applications areas and business opportunities for analytical technology in hand held, mobile and on-line applications. Advances in microfabrication have resulted in high-performance MEMS and MOEMS devices for spectrometer applications. Many other enabling technologies are useful for miniature analytical solutions, such as silicon photonics, nanoimprint lithography (NIL), system-on-chip, system-on-package techniques for integration of electronics and photonics, 3D printing, powerful embedded computing platforms, networked solutions as well as advances in chemometrics modeling. This paper will summarize recent work on spectrometer and sensor miniaturization at VTT Technical Research Centre of Finland. Fabry-Perot interferometer (FPI) tunable filter technology has been developed in two technical versions: Piezoactuated FPIs have been applied in miniature hyperspectral imaging needs in light weight UAV and nanosatellite applications, chemical imaging as well as medical applications. Microfabricated MOEMS FPIs have been developed as cost-effective sensor platforms for visible, NIR and IR applications. Further examples of sensor miniaturization will be discussed, including system-on-package sensor head for mid-IR gas analyzer, roll-to-roll printed Surface Enhanced Raman Scattering (SERS) technology as well as UV imprinted waveguide sensor for formaldehyde detection.

  14. Synaptic adaptations to chronic ethanol intake in male rhesus monkey dorsal striatum depend on age of drinking onset.

    Science.gov (United States)

    Cuzon Carlson, Verginia C; Grant, Kathleen A; Lovinger, David M

    2018-03-15

    One in 12 adults suffer with alcohol use disorder (AUD). Studies suggest the younger the age in which alcohol consumption begins the higher the probability of being diagnosed with AUD. Binge/excessive alcohol drinking involves a transition from flexible to inflexible behavior likely involving the dorsal striatum (caudate and putamen nuclei). A major focus of this study was to examine the effect of age of drinking onset on subsequent chronic, voluntary ethanol intake and dorsal striatal circuitry. Data from rhesus monkeys (n = 45) that started drinking as adolescents, young adults or mature adults confirms an age-related risk for heavy drinking. Striatal neuroadaptations were examined using whole-cell patch clamp electrophysiology to record AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) and GABA A receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) from medium-sized spiny projection neurons located in the caudate or putamen nuclei. In controls, greater GABAergic transmission (mIPSC frequency and amplitude) was observed in the putamen compared to the caudate. With advancing age, in the absence of ethanol, an increase in mIPSC frequency concomitant with changes in mIPSC amplitude was observed in both regions. Chronic ethanol drinking decreased mIPSC frequency in the putamen regardless of age of onset. In the caudate, an ethanol drinking-induced increase in mIPSC frequency was only observed in monkeys that began drinking as young adults. Glutamatergic transmission did not differ between the dorsal striatal subregions in controls. With chronic ethanol drinking there was a decrease in the postsynaptic characteristics of rise time and area of mEPSCs in the putamen but an increase in mEPSC frequency in the caudate. Together, the observed changes in striatal physiology indicate a combined disinhibition due to youth and ethanol leading to abnormally strong activation of the putamen that could contribute to the increased risk

  15. Miniature excitatory synaptic currents in cultured hippocampal neurons.

    Science.gov (United States)

    Finch, D M; Fisher, R S; Jackson, M B

    1990-06-04

    We performed patch clamp recordings in the whole cell mode from cultured embryonic mouse hippocampal neurons. In bathing solutions containing tetrodotoxin (TTX), the cells showed spontaneous inward currents (SICs) ranging in size from 1 to 100 pA. Several observations indicated that the SICs were miniature excitatory synaptic currents mediated primarily by non-NMDA (N-methyl-D-aspartate) excitatory amino acid receptors: the rising phase of SICs was fast (1 ms to half amplitude at room temperature) and smooth, suggesting unitary events. The SICs were blocked by the broad-spectrum glutamate receptor antagonist gamma-D-glutamylglycine (DGG), but not by the selective NMDA-receptor antagonist D-2-amino-5-phosphonovaleric acid (5-APV). SICs were also blocked by desensitizing concentrations of quisqualate. Incubating cells in tetanus toxin, which blocks exocytotic transmitter release, eliminated SICs. The presence of SICs was consistent with the morphological arrangement of glutamatergic innervation in the cell cultures demonstrated immunohistochemically. Spontaneous outward currents (SOCs) were blocked by bicuculline and presumed to be mediated by GABAA receptors. This is consistent with immunohistochemical demonstration of GABAergic synapses. SIC frequency was increased in a calcium dependent manner by bathing the cells in a solution high in K+, and application of the dihydropyridine L-type calcium channel agonist BAY K 8644 increased the frequency of SICs. Increases in SIC frequency produced by high K+ solutions were reversed by Cd2+ and omega-conotoxin GVIA, but not by the selective L-type channel antagonist nimodipine. This suggested that presynaptic L-type channels were in a gating mode that was not blocked by nimodipine, and/or that another class of calcium channel makes a dominant contribution to excitatory transmitter release.

  16. Electrophysiological evidence of increased glycine receptor-mediated phasic and tonic inhibition by blockade of glycine transporters in spinal superficial dorsal horn neurons of adult mice

    Directory of Open Access Journals (Sweden)

    Misa Oyama

    2017-03-01

    Full Text Available To understand the synaptic and/or extrasynaptic mechanisms underlying pain relief by blockade of glycine transporter subtypes GlyT1 and GlyT2, whole-cell recordings were made from dorsal horn neurons in spinal slices from adult mice, and the effects of NFPS and ALX-1393, selective GlyT1 and GlyT2 inhibitors, respectively, on phasic evoked or miniature glycinergic inhibitory postsynaptic currents (eIPSCs or mIPSCs were examined. NFPS and ALX-1393 prolonged the decay phase of eIPSCs without affecting their amplitude. In the presence of tetrodotoxin to record mIPSCs, NFPS and ALX-1393 induced a tonic inward current that was reversed by strychnine. Although NFPS had no statistically significant influences on mIPSCs, ALX-1393 significantly increased their frequency. We then further explored the role of GlyTs in the maintenance of glycinergic IPSCs. To facilitate vesicular release of glycine, repetitive high-frequency stimulation (HFS was applied at 10 Hz for 3 min during continuous recordings of eIPSCs at 0.1 Hz. Prominent suppression of eIPSCs was evident after HFS in the presence of ALX-1393, but not NFPS. Thus, it appears that phasic and tonic inhibition may contribute to the analgesic effects of GlyT inhibitors. However, reduced glycinergic inhibition due to impaired vesicular refilling could hamper the analgesic efficacy of GlyT2 inhibitors.

  17. Neurons derived from sporadic Alzheimer's disease iPSCs reveal elevated TAU hyperphosphorylation, increased amyloid levels, and GSK3B activation

    DEFF Research Database (Denmark)

    Ochalek, Anna; Mihalik, Balázs; Avci, Hasan X.

    2017-01-01

    , our aim was to establish an in vitro cell model based on patient-specific human neurons to study the pathomechanism of sporadic AD. Methods: We compared neurons derived from induced pluripotent stem cell (iPSC) lines of patients with early-onset familial Alzheimer's disease (fAD), all caused...... blotting methods. Results: Neurons from patients with fAD and patients with sAD showed increased phosphorylation of TAU protein at all investigated phosphorylation sites. Relative to the control neurons, neurons derived from patients with fAD and patients with sAD exhibited higher levels of extracellular......, a physiological kinase of TAU, in neurons derived from AD iPSCs, as well as significant upregulation of amyloid precursor protein (APP) synthesis and APP carboxy-terminal fragment cleavage. Moreover, elevated sensitivity to oxidative stress, as induced by amyloid oligomers or peroxide, was detected in both f...

  18. Adolescent maturation of inhibitory inputs onto cingulate cortex neurons is cell-type specific and TrkB dependent

    Directory of Open Access Journals (Sweden)

    Angela eVandenberg

    2015-02-01

    Full Text Available The maturation of inhibitory circuits during adolescence may be tied to the onset of mental health disorders such as schizophrenia. Neurotrophin signaling likely plays a critical role in supporting inhibitory circuit development and is also implicated in psychiatric disease. Within the neocortex, subcircuits may mature at different times and show differential sensitivity to neurotrophin signaling. We measured miniature inhibitory and excitatory postsynaptic currents (mIPSC and mEPSCs in Layer 5 cell-types in the mouse anterior cingulate across the periadolescent period. We differentiated cell-types mainly by Thy1 YFP transgene expression and also retrobead injection labeling in the contralateral cingulate and ipsilateral pons. We found that YFP- neurons and commissural projecting neurons had lower frequency of mIPSCs than neighboring YFP+ neurons or pons projecting neurons in juvenile mice (P21-25. YFP- neurons and to a lesser extent commissural projecting neurons also showed a significant increase in mIPSC amplitude during the periadolescent period (P21-25 vs. P40-50, which was not seen in YFP+ neurons or pons projecting neurons. Systemic disruption of tyrosine kinase receptor B (TrkB signaling during P23-50 in TrkBF616A mice blocked developmental changes in mIPSC amplitude, without affecting miniature excitatory post synaptic currents (mEPSCs. Our data suggest that the maturation of inhibitory inputs onto layer 5 pyramidal neurons is cell-type specific. These data may inform our understanding of adolescent brain development across species and aid in identifying candidate subcircuits that may show greater vulnerability in mental illness.

  19. Miniaturized GPS/MEMS IMU integrated board

    Science.gov (United States)

    Lin, Ching-Fang (Inventor)

    2012-01-01

    This invention documents the efforts on the research and development of a miniaturized GPS/MEMS IMU integrated navigation system. A miniaturized GPS/MEMS IMU integrated navigation system is presented; Laser Dynamic Range Imager (LDRI) based alignment algorithm for space applications is discussed. Two navigation cameras are also included to measure the range and range rate which can be integrated into the GPS/MEMS IMU system to enhance the navigation solution.

  20. Miniaturizing RFID for magnamosis.

    Science.gov (United States)

    Jiang, Hao; Chen, Shijie; Kish, Shad; Loh, Lokkee; Zhang, Junmin; Zhang, Xiaorong; Kwiat, Dillon; Harrison, Michael; Roy, Shuvo

    2014-01-01

    Anastomosis is a common surgical procedure using staples or sutures in an open or laparoscopic surgery. A more effective and much less invasive alternative is to apply the mechanical pressure on the tissue over a few days [1]. Since the pressure is produced by the attractive force between two permanent magnets, the procedure is called magnamosis[1]. To ensure the two magnets are perfectly aligned during the surgery, a miniaturized batteryless Radio Frequency IDentification (RFID) tag is developed to wirelessly telemeter the status of a pressure sensitive mechanical switch. Using the multi-layer circular spiral coil design, the diameter of the RFID tag is shrunk to 10, 15, 19 and 27 mm to support the magnamosis for children as well as adults. With the impedance matching network, the operating distance of these four RFID tags are longer than 10 cm in a 20 × 22 cm(2) area, even when the tag's normal direction is 45° off the antenna's normal direction. Measurement results also indicate that there is no noticeable degradation on the operating distance when the tag is immersed in saline or placed next to the rare-earth magnet. The miniaturized RFID tag presented in this paper is able to support the magnamosis and other medical applications that require the miniaturized RFID tag.

  1. Acute morphine alters GABAergic transmission in the central amygdala during naloxone-precipitated morphine withdrawal: role of cyclic AMP

    Directory of Open Access Journals (Sweden)

    Michal eBajo

    2014-06-01

    Full Text Available The central amygdala (CeA plays an important role in opioid addiction. Therefore, we examined the effects of naloxone-precipitated morphine withdrawal (WD on GABAergic transmission in rat CeA neurons using whole-cell recordings with naloxone in the bath. The basal frequency of miniature inhibitory postsynaptic currents (mIPSCs increased in CeA neurons from WD compared to placebo rats. Acute morphine (10 M had mixed effects (> 20% change from baseline on mIPSCs in placebo and WD rats. In most CeA neurons (64% from placebo rats, morphine significantly decreased mIPSC frequency and amplitude. In 32% of placebo neurons, morphine significantly increased mIPSC amplitudes but had no effect on mIPSC frequency. In WD rats, acute morphine significantly increased mIPSC frequency but had no effect on mIPSC amplitude in 41% of CeA neurons. In 45% of cells, acute morphine significantly decreased mIPSC frequency and amplitude. Pre-treatment with the cyclic AMP inhibitor (R-adenosine, cyclic 3’,5’-(hydrogenphosphorothioate triethylammonium (RP, prevented acute morphine-induced potentiation of mIPSCs. Pre-treatment of slices with the Gi/o G-protein subunit inhibitor pertussis toxin (PTX did not prevent the acute morphine-induced enhancement or inhibition of mIPSCs. PTX and RP decreased basal mIPSC frequencies and amplitudes only in WD rats. The results suggest that inhibition of GABAergic transmission in the CeA by acute morphine is mediated by PTX-insensitive mechanisms, although PTX-sensitive mechanisms cannot be ruled out for non-morphine responsive cells; by contrast, potentiation of GABAergic transmission is mediated by activated cAMP signaling that also mediates the increased basal GABAergic transmission in WD rats. Our data indicate that during the acute phase of WD, the CeA opioid and GABAergic systems undergo neuroadaptative changes conditioned by a previous chronic morphine exposure and dependence.

  2. Nuclear Energy Advanced Modeling and Simulation (NEAMS) waste Integrated Performance and Safety Codes (IPSC): gap analysis for high fidelity and performance assessment code development

    International Nuclear Information System (INIS)

    Lee, Joon H.; Siegel, Malcolm Dean; Arguello, Jose Guadalupe Jr.; Webb, Stephen Walter; Dewers, Thomas A.; Mariner, Paul E.; Edwards, Harold Carter; Fuller, Timothy J.; Freeze, Geoffrey A.; Jove-Colon, Carlos F.; Wang, Yifeng

    2011-01-01

    This report describes a gap analysis performed in the process of developing the Waste Integrated Performance and Safety Codes (IPSC) in support of the U.S. Department of Energy (DOE) Office of Nuclear Energy Advanced Modeling and Simulation (NEAMS) Campaign. The goal of the Waste IPSC is to develop an integrated suite of computational modeling and simulation capabilities to quantitatively assess the long-term performance of waste forms in the engineered and geologic environments of a radioactive waste storage or disposal system. The Waste IPSC will provide this simulation capability (1) for a range of disposal concepts, waste form types, engineered repository designs, and geologic settings, (2) for a range of time scales and distances, (3) with appropriate consideration of the inherent uncertainties, and (4) in accordance with rigorous verification, validation, and software quality requirements. The gap analyses documented in this report were are performed during an initial gap analysis to identify candidate codes and tools to support the development and integration of the Waste IPSC, and during follow-on activities that delved into more detailed assessments of the various codes that were acquired, studied, and tested. The current Waste IPSC strategy is to acquire and integrate the necessary Waste IPSC capabilities wherever feasible, and develop only those capabilities that cannot be acquired or suitably integrated, verified, or validated. The gap analysis indicates that significant capabilities may already exist in the existing THC codes although there is no single code able to fully account for all physical and chemical processes involved in a waste disposal system. Large gaps exist in modeling chemical processes and their couplings with other processes. The coupling of chemical processes with flow transport and mechanical deformation remains challenging. The data for extreme environments (e.g., for elevated temperature and high ionic strength media) that are

  3. Nuclear Energy Advanced Modeling and Simulation (NEAMS) waste Integrated Performance and Safety Codes (IPSC) : gap analysis for high fidelity and performance assessment code development.

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joon H.; Siegel, Malcolm Dean; Arguello, Jose Guadalupe, Jr.; Webb, Stephen Walter; Dewers, Thomas A.; Mariner, Paul E.; Edwards, Harold Carter; Fuller, Timothy J.; Freeze, Geoffrey A.; Jove-Colon, Carlos F.; Wang, Yifeng

    2011-03-01

    This report describes a gap analysis performed in the process of developing the Waste Integrated Performance and Safety Codes (IPSC) in support of the U.S. Department of Energy (DOE) Office of Nuclear Energy Advanced Modeling and Simulation (NEAMS) Campaign. The goal of the Waste IPSC is to develop an integrated suite of computational modeling and simulation capabilities to quantitatively assess the long-term performance of waste forms in the engineered and geologic environments of a radioactive waste storage or disposal system. The Waste IPSC will provide this simulation capability (1) for a range of disposal concepts, waste form types, engineered repository designs, and geologic settings, (2) for a range of time scales and distances, (3) with appropriate consideration of the inherent uncertainties, and (4) in accordance with rigorous verification, validation, and software quality requirements. The gap analyses documented in this report were are performed during an initial gap analysis to identify candidate codes and tools to support the development and integration of the Waste IPSC, and during follow-on activities that delved into more detailed assessments of the various codes that were acquired, studied, and tested. The current Waste IPSC strategy is to acquire and integrate the necessary Waste IPSC capabilities wherever feasible, and develop only those capabilities that cannot be acquired or suitably integrated, verified, or validated. The gap analysis indicates that significant capabilities may already exist in the existing THC codes although there is no single code able to fully account for all physical and chemical processes involved in a waste disposal system. Large gaps exist in modeling chemical processes and their couplings with other processes. The coupling of chemical processes with flow transport and mechanical deformation remains challenging. The data for extreme environments (e.g., for elevated temperature and high ionic strength media) that are

  4. Miniature x-ray source

    Science.gov (United States)

    Trebes, James E.; Bell, Perry M.; Robinson, Ronald B.

    2000-01-01

    A miniature x-ray source utilizing a hot filament cathode. The source has a millimeter scale size and is capable of producing broad spectrum x-ray emission over a wide range of x-ray energies. The miniature source consists of a compact vacuum tube assembly containing the hot filament cathode, an anode, a high voltage feedthru for delivering high voltage to the cathode, a getter for maintaining high vacuum, a connector for initial vacuum pump down and crimp-off, and a high voltage connection for attaching a compact high voltage cable to the high voltage feedthru. At least a portion of the vacuum tube wall is fabricated from highly x-ray transparent materials, such as sapphire, diamond, or boron nitride.

  5. Neurosphere based differentiation of human iPSC improves astrocyte differentiation

    DEFF Research Database (Denmark)

    Zhou, Shuling; Szczesna, Karolina; Ochalek, Anna

    2016-01-01

    Neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) are traditionally maintained and proliferated utilizing two-dimensional (2D) adherent monolayer culture systems. However, NPCs cultured using this system hardly reflect the intrinsic spatial development...... of brain tissue. In this study, we determined that culturing iPSC-derived NPCs as three-dimensional (3D) floating neurospheres resulted in increased expression of the neural progenitor cell (NPC) markers, PAX6 and NESTIN. Expansion of NPCs in 3D culture methods also resulted in a more homogenous PAX6...... expression when compared to 2D culture methods. Furthermore, the 3D propagation method for NPCs resulted in a significant higher expression of the astrocyte markers  GFAP and aquaporin 4 (AQP4) in the differentiated cells. Thus, our 3D propagation method could constitute a useful tool to promote NPC...

  6. The TLX-miR-219 cascade regulates neural stem cell proliferation in neurodevelopment and schizophrenia iPSC model.

    Science.gov (United States)

    Murai, Kiyohito; Sun, Guoqiang; Ye, Peng; Tian, E; Yang, Su; Cui, Qi; Sun, Guihua; Trinh, Daniel; Sun, Olivia; Hong, Teresa; Wen, Zhexing; Kalkum, Markus; Riggs, Arthur D; Song, Hongjun; Ming, Guo-li; Shi, Yanhong

    2016-03-11

    Dysregulated expression of miR-219, a brain-specific microRNA, has been observed in neurodevelopmental disorders, such as schizophrenia (SCZ). However, its role in normal mammalian neural stem cells (NSCs) and in SCZ pathogenesis remains unknown. We show here that the nuclear receptor TLX, an essential regulator of NSC proliferation and self-renewal, inhibits miR-219 processing. miR-219 suppresses mouse NSC proliferation downstream of TLX. Moreover, we demonstrate upregulation of miR-219 and downregulation of TLX expression in NSCs derived from SCZ patient iPSCs and DISC1-mutant isogenic iPSCs. SCZ NSCs exhibit reduced cell proliferation. Overexpression of TLX or inhibition of miR-219 action rescues the proliferative defect in SCZ NSCs. Therefore, this study uncovers an important role for TLX and miR-219 in both normal neurodevelopment and in SCZ patient iPSC-derived NSCs. Moreover, this study reveals an unexpected role for TLX in regulating microRNA processing, independent of its well-characterized role in transcriptional regulation.

  7. Miniature mass analyzer

    CERN Document Server

    Cuna, C; Lupsa, N; Cuna, S; Tuzson, B

    2003-01-01

    The paper presents the concept of different mass analyzers that were specifically designed as small dimension instruments able to detect with great sensitivity and accuracy the main environmental pollutants. The mass spectrometers are very suited instrument for chemical and isotopic analysis, needed in environmental surveillance. Usually, this is done by sampling the soil, air or water followed by laboratory analysis. To avoid drawbacks caused by sample alteration during the sampling process and transport, the 'in situ' analysis is preferred. Theoretically, any type of mass analyzer can be miniaturized, but some are more appropriate than others. Quadrupole mass filter and trap, magnetic sector, time-of-flight and ion cyclotron mass analyzers can be successfully shrunk, for each of them some performances being sacrificed but we must know which parameters are necessary to be kept unchanged. To satisfy the miniaturization criteria of the analyzer, it is necessary to use asymmetrical geometries, with ion beam obl...

  8. Novel lipoprotein density profiling in healthy dogs of various breeds, healthy miniature schnauzers, and miniature schnauzers with hyperlipidemia

    Science.gov (United States)

    2013-01-01

    Background Despite the importance of abnormalities in lipoprotein metabolism in clinical canine medicine, the fact that most previously used methods for lipoprotein profiling are rather laborious and time-consuming has been a major obstacle to the wide clinical application and use of lipoprotein profiling in this species. The aim of the present study was to assess the feasibility of a continuous lipoprotein density profile (CLPDP) generated within a bismuth sodium ethylenediaminetetraacetic acid (NaBiEDTA) density gradient to characterize and compare the lipoprotein profiles of healthy dogs of various breeds, healthy Miniature Schnauzers, and Miniature Schnauzers with primary hypertriacylglycerolemia. A total of 35 healthy dogs of various breeds with serum triacylglycerol (TAG) and cholesterol concentrations within their respective reference intervals were selected for use as a reference population. Thirty-one Miniature Schnauzers with serum TAG and cholesterol concentrations within their respective reference intervals and 31 Miniature Schnauzers with hypertriacylglyceridemia were also included in the study. Results The results suggest that CLPDP using NaBiEDTA provides unique diagnostic information in addition to measurements of serum TAG and cholesterol concentrations and that it is a useful screening method for dogs with suspected lipoprotein metabolism disorders. Using the detailed and continuous density distribution information provided by the CLPDP, important differences in lipoprotein profiles can be detected even among dogs that have serum TAG and cholesterol concentrations within the reference interval. Miniature Schnauzers with serum TAG and cholesterol concentrations within the reference interval had significantly different lipoprotein profiles than dogs of various other breeds. In addition, it was further established that specific lipoprotein fractions are associated with hypertriacylglyceridemia in Miniature Schnauzers. Conclusions The results of the

  9. Miniature Scroll Pumps Fabricated by LIGA

    Science.gov (United States)

    Wiberg, Dean; Shcheglov, Kirill; White, Victor; Bae, Sam

    2009-01-01

    Miniature scroll pumps have been proposed as roughing pumps (low - vacuum pumps) for miniature scientific instruments (e.g., portable mass spectrometers and gas analyzers) that depend on vacuum. The larger scroll pumps used as roughing pumps in some older vacuum systems are fabricated by conventional machining. Typically, such an older scroll pump includes (1) an electric motor with an eccentric shaft to generate orbital motion of a scroll and (2) conventional bearings to restrict the orbital motion to a circle. The proposed miniature scroll pumps would differ from the prior, larger ones in both design and fabrication. A miniature scroll pump would include two scrolls: one mounted on a stationary baseplate and one on a flexure stage (see figure). An electromagnetic actuator in the form of two pairs of voice coils in a push-pull configuration would make the flexure stage move in the desired circular orbit. The capacitance between the scrolls would be monitored to provide position (gap) feedback to a control system that would adjust the drive signals applied to the voice coils to maintain the circular orbit as needed for precise sealing of the scrolls. To minimize power consumption and maximize precision of control, the flexure stage would be driven at the frequency of its mechanical resonance. The miniaturization of these pumps would entail both operational and manufacturing tolerances of pump components. In addition, the vibrations of conventional motors and ball bearings exceed these tight tolerances by an order of magnitude. Therefore, the proposed pumps would be fabricated by the microfabrication method known by the German acronym LIGA ( lithographie, galvanoformung, abformung, which means lithography, electroforming, molding) because LIGA has been shown to be capable of providing the required tolerances at large aspect ratios.

  10. Fast and Slow Inhibition in the Visual Thalamus Is Influenced by Allocating GABAA Receptors with Different γ Subunits

    Directory of Open Access Journals (Sweden)

    Zhiwen Ye

    2017-04-01

    Full Text Available Cell-type specific differences in the kinetics of inhibitory postsynaptic conductance changes (IPSCs are believed to impact upon network dynamics throughout the brain. Much attention has focused on how GABAA receptor (GABAAR α and β subunit diversity will influence IPSC kinetics, but less is known about the influence of the γ subunit. We have examined whether GABAAR γ subunit heterogeneity influences IPSC properties in the thalamus. The γ2 subunit gene was deleted from GABAARs selectively in the dorsal lateral geniculate nucleus (dLGN. The removal of the γ2 subunit from the dLGN reduced the overall spontaneous IPSC (sIPSC frequency across all relay cells and produced an absence of IPSCs in a subset of relay neurons. The remaining slower IPSCs were both insensitive to diazepam and zinc indicating the absence of the γ2 subunit. Because these slower IPSCs were potentiated by methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM, we propose these IPSCs involve γ1 subunit-containing GABAAR activation. Therefore, γ subunit heterogeneity appears to influence the kinetics of GABAAR-mediated synaptic transmission in the visual thalamus in a cell-selective manner. We suggest that activation of γ1 subunit-containing GABAARs give rise to slower IPSCs in general, while faster IPSCs tend to be mediated by γ2 subunit-containing GABAARs.

  11. A parallel implementation of particle tracking with space charge effects on an INTEL iPSC/860

    International Nuclear Information System (INIS)

    Chang, L.; Bourianoff, G.; Cole, B.; Machida, S.

    1993-05-01

    Particle-tracking simulation is one of the scientific applications that is well-suited to parallel computations. At the Superconducting Super Collider, it has been theoretically and empirically demonstrated that particle tracking on a designed lattice can achieve very high parallel efficiency on a MIMD Intel iPSC/860 machine. The key to such success is the realization that the particles can be tracked independently without considering their interaction. The perfectly parallel nature of particle tracking is broken if the interaction effects between particles are included. The space charge introduces an electromagnetic force that will affect the motion of tracked particles in 3-D space. For accurate modeling of the beam dynamics with space charge effects, one needs to solve three-dimensional Maxwell field equations, usually by a particle-in-cell (PIC) algorithm. This will require each particle to communicate with its neighbor grids to compute the momentum changes at each time step. It is expected that the 3-D PIC method will degrade parallel efficiency of particle-tracking implementation on any parallel computer. In this paper, we describe an efficient scheme for implementing particle tracking with space charge effects on an INTEL iPSC/860 machine. Experimental results show that a parallel efficiency of 75% can be obtained

  12. FY 2006 Miniature Spherical Retroreflectors Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Anheier, Norman C.; Bernacki, Bruce E.; Krishnaswami, Kannan

    2006-12-28

    Research done by the Infrared Photonics team at Pacific Northwest National Laboratory (PNNL) is focused on developing miniature spherical retroreflectors using the unique optical and material properties of chalcogenide glass to reduce both performance limiting spherical aberrations. The optimized optical performance will provide efficient signal retroreflection that enables a broad range of remote detection scenarios for mid-wave infrared (MWIR) and long-wave infrared (LWIR) sensing applications. Miniature spherical retroreflectors can be developed to aid in the detection of signatures of nuclear proliferation or other chemical vapor or radiation signatures. Miniature spherical retroreflectors are not only well suited to traditional LIDAR methods for chemical plume detection and identification, but could enable remote detection of difficult semi-volatile chemical materials or low level radiation sources.

  13. Nootropic agents enhance the recruitment of fast GABAA inhibition in rat neocortex.

    Science.gov (United States)

    Ling, Douglas S F; Benardo, Larry S

    2005-07-01

    It is widely believed that nootropic (cognition-enhancing) agents produce their therapeutic effects by augmenting excitatory synaptic transmission in cortical circuits, primarily through positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors (AMPARs). However, GABA-mediated inhibition is also critical for cognition, and enhanced GABA function may be likewise therapeutic for cognitive disorders. Could nootropics act through such a mechanism as well? To address this question, we examined the effects of nootropic agents on excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) recorded from layer V pyramidal cells in acute slices of somatosensory cortex. Aniracetam, a positive modulator of AMPA/kainate receptors, increased the peak amplitude of evoked EPSCs and the amplitude and duration of polysynaptic fast IPSCs, manifested as a greater total charge carried by IPSCs. As a result, the EPSC/IPSC ratio of total charge was decreased, representing a shift in the excitation-inhibition balance that favors inhibition. Aniracetam did not affect the magnitude of either monosynaptic IPSCs (mono-IPSCs) recorded in the presence of excitatory amino acid receptor antagonists, or miniature IPSCs (mIPSCs) recorded in the presence of tetrodotoxin. However, the duration of both mono-IPSCs and mIPSCs was prolonged, suggesting that aniracetam also directly modulates GABAergic transmission. Cyclothiazide, a preferential modulator of AMPAR function, enhanced the magnitude and duration of polysynaptic IPSCs, similar to aniracetam, but did not affect mono-IPSCs. Concanavalin A, a kainate receptor modulator, had little effect on EPSCs or IPSCs, suggesting there was no contribution from kainate receptor activity. These findings indicate that AMPAR modulators strengthen inhibition in neocortical pyramidal cells, most likely by altering the kinetics of AMPARs on synaptically connected interneurons and possibly by modulating GABA(A) receptor responses

  14. Miniature radioactive light source

    International Nuclear Information System (INIS)

    Caffarella, T.E.; Radda, G.J.; Dooley, H.H.

    1980-01-01

    A miniature radioactive light source for illuminating digital watches is described consisting of a glass tube with improved laser sealing and strength containing tritium gas and a transducer responsive to the gas. (U.K.)

  15. Generation of induced pluripotent stem cells (iPSCs) stably expressing CRISPR-based synergistic activation mediator (SAM)

    DEFF Research Database (Denmark)

    Xiong, Kai; Zhou, Yan; Hyttel, Poul

    2016-01-01

    Human fibroblasts were engineered to express the CRISPR-based synergistic activation mediator (SAM) complex: dCas9-VP64 and MS2-P65-HSF1. Two induced pluripotent stem cells (iPSCs) clones expressing SAM were established by transducing these fibroblasts with lentivirus expressing OCT4, SOX2, KLF4...... a novel, useful tool to investigate genetic regulation of stem cell proliferation and differentiation through CRISPR-mediated activation of endogenous genes....

  16. Presynaptic miniature GABAergic currents in developing interneurons.

    Science.gov (United States)

    Trigo, Federico F; Bouhours, Brice; Rostaing, Philippe; Papageorgiou, George; Corrie, John E T; Triller, Antoine; Ogden, David; Marty, Alain

    2010-04-29

    Miniature synaptic currents have long been known to represent random transmitter release under resting conditions, but much remains to be learned about their nature and function in central synapses. In this work, we describe a new class of miniature currents ("preminis") that arise by the autocrine activation of axonal receptors following random vesicular release. Preminis are prominent in gabaergic synapses made by cerebellar interneurons during the development of the molecular layer. Unlike ordinary miniature postsynaptic currents in the same cells, premini frequencies are strongly enhanced by subthreshold depolarization, suggesting that the membrane depolarization they produce belongs to a feedback loop regulating neurotransmitter release. Thus, preminis could guide the formation of the interneuron network by enhancing neurotransmitter release at recently formed synaptic contacts. Copyright 2010 Elsevier Inc. All rights reserved.

  17. Miniature Centrifugal Compressor

    Science.gov (United States)

    Sixsmith, Herbert

    1989-01-01

    Miniature turbocompressor designed for reliability and long life. Cryogenic system includes compressor, turboexpander, and heat exchanger provides 5 W of refrigeration at 70 K from 150 W input power. Design speed of machine 510,000 rpm. Compressor has gas-lubricated journal bearings and magnetic thrust bearing. When compressor runs no bearing contact and no wear.

  18. Goniometry and Limb Girth in Miniature Dachshunds

    OpenAIRE

    Thomovsky, Stephanie A.; Chen, Annie V.; Kiszonas, Alecia M.; Lutskas, Lori A.

    2016-01-01

    Purpose. To report the mean and median pelvic limb joint angles and girth measurements in miniature Dachshunds presenting with varying degrees of pelvic limb weakness secondary to thoracolumbar intervertebral disc extrusion. Methods. 15 miniature Dachshunds who presented to WSU-VTH for thoracolumbar disc extrusion. Dachshunds varied in neurologic status from ambulatory paraparetic to paraplegic at the time of measurements. Results. There were no significant differences in joint angles or girt...

  19. Miniaturized Environmental Monitoring Instrumentation

    Energy Technology Data Exchange (ETDEWEB)

    C. B. Freidhoff

    1997-09-01

    The objective of the Mass Spectrograph on a Chip (MSOC) program is the development of a miniature, multi-species gas sensor fabricated using silicon micromachining technology which will be orders of magnitude smaller and lower power consumption than a conventional mass spectrometer. The sensing and discrimination of this gas sensor are based on an ionic mass spectrograph, using magnetic and/or electrostatic fields. The fields cause a spatial separation of the ions according to their respective mass-to-charge ratio. The fabrication of this device involves the combination of microelectronics with micromechanically built sensors and, ultimately, vacuum pumps. The prototype of a chemical sensor would revolutionize the method of performing environmental monitoring for both commercial and government applications. The portable unit decided upon was the miniaturized gas chromatograph with a mass spectrometer detector, referred to as a GC/MS in the analytical marketplace.

  20. Antenna Miniaturization with MEMS Tunable Capacitors

    DEFF Research Database (Denmark)

    Barrio, Samantha Caporal Del; Morris, Art; Pedersen, Gert Frølund

    2014-01-01

    In today’s mobile device market, there is a strong need for efficient antenna miniaturization. Tunable antennas are a very promising way to reduce antenna volume while enlarging its operating bandwidth. MEMS tunable capacitors are state-ofthe- art in terms of insertion loss and their characterist......In today’s mobile device market, there is a strong need for efficient antenna miniaturization. Tunable antennas are a very promising way to reduce antenna volume while enlarging its operating bandwidth. MEMS tunable capacitors are state-ofthe- art in terms of insertion loss...

  1. Nuclear Energy Advanced Modeling and Simulation Waste Integrated Performance and Safety Codes (NEAMS Waste IPSC).

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, Peter Andrew

    2011-12-01

    The objective of the U.S. Department of Energy Office of Nuclear Energy Advanced Modeling and Simulation Waste Integrated Performance and Safety Codes (NEAMS Waste IPSC) is to provide an integrated suite of computational modeling and simulation (M&S) capabilities to quantitatively assess the long-term performance of waste forms in the engineered and geologic environments of a radioactive-waste storage facility or disposal repository. Achieving the objective of modeling the performance of a disposal scenario requires describing processes involved in waste form degradation and radionuclide release at the subcontinuum scale, beginning with mechanistic descriptions of chemical reactions and chemical kinetics at the atomic scale, and upscaling into effective, validated constitutive models for input to high-fidelity continuum scale codes for coupled multiphysics simulations of release and transport. Verification and validation (V&V) is required throughout the system to establish evidence-based metrics for the level of confidence in M&S codes and capabilities, including at the subcontiunuum scale and the constitutive models they inform or generate. This Report outlines the nature of the V&V challenge at the subcontinuum scale, an approach to incorporate V&V concepts into subcontinuum scale modeling and simulation (M&S), and a plan to incrementally incorporate effective V&V into subcontinuum scale M&S destined for use in the NEAMS Waste IPSC work flow to meet requirements of quantitative confidence in the constitutive models informed by subcontinuum scale phenomena.

  2. Nuclear Energy Advanced Modeling and Simulation Waste Integrated Performance and Safety Codes (NEAMS Waste IPSC)

    International Nuclear Information System (INIS)

    Schultz, Peter Andrew

    2011-01-01

    The objective of the U.S. Department of Energy Office of Nuclear Energy Advanced Modeling and Simulation Waste Integrated Performance and Safety Codes (NEAMS Waste IPSC) is to provide an integrated suite of computational modeling and simulation (M and S) capabilities to quantitatively assess the long-term performance of waste forms in the engineered and geologic environments of a radioactive-waste storage facility or disposal repository. Achieving the objective of modeling the performance of a disposal scenario requires describing processes involved in waste form degradation and radionuclide release at the subcontinuum scale, beginning with mechanistic descriptions of chemical reactions and chemical kinetics at the atomic scale, and upscaling into effective, validated constitutive models for input to high-fidelity continuum scale codes for coupled multiphysics simulations of release and transport. Verification and validation (V and V) is required throughout the system to establish evidence-based metrics for the level of confidence in M and S codes and capabilities, including at the subcontiunuum scale and the constitutive models they inform or generate. This Report outlines the nature of the V and V challenge at the subcontinuum scale, an approach to incorporate V and V concepts into subcontinuum scale modeling and simulation (M and S), and a plan to incrementally incorporate effective V and V into subcontinuum scale M and S destined for use in the NEAMS Waste IPSC work flow to meet requirements of quantitative confidence in the constitutive models informed by subcontinuum scale phenomena.

  3. Research on Miniature Calibre Rail-Guns for the Mechanical Arm

    Directory of Open Access Journals (Sweden)

    Ronggang Cao

    2017-01-01

    Full Text Available Rail-gun should not only be used to military applications, but also can be developed as applications in the civilian aspects of the market. With the development of the electromagnetic launch technology, based on the similarity theory, using the existing rail-gun model to guide the construction of more economical miniature calibre rail-guns, and apply it in some machinery and equipment, this idea will open up a wider rail-gun application space. This article will focus on the feasibility of application of miniature calibre rail-guns in the mechanical arm. This paper designs the schematic diagram, then theoretical analyzes force conditions of the armature in the mechanical arm, calculates the possible range of the current amplitude and so on. The existing rail-gun model can be used to guides design the circuit diagram of the miniature calibre rail-gun. Based on the similarity theory and many simulation experiments, designed the experimental parameters of a miniature rail-gun and analyzed the current, Lorentz force, velocity, and location of the existing rail-gun and miniature rail-gun. The results show that the rail-gun launching technology applied to robot arms is feasibility. The application of miniature calibre rail-guns in the mechanical arm will benefit to the further development of rail-guns.

  4. Plasma turbulence calculations on the Intel iPSC/860 (rx) hypercube

    International Nuclear Information System (INIS)

    Lynch, V.E.; Ruiter, J.R.

    1990-01-01

    One approach to improving the real-time efficiency of plasma turbulence calculations is to use a parallel algorithm. A serial algorithm used for plasma turbulence calculations was modified to allocate a radial region in each node. In this way, convolutions at a fixed radius are performed in parallel, and communication is limited to boundary values for each radial region. For a semi-implicity numerical scheme (tridiagonal matrix solver), there is a factor of 3 improvement in efficiency with the Intel iPSC/860 machine using 64 processors over a single-processor Cray-II. For block-tridiagonal matrix cases (fully implicit code), a second parallelization takes place. The Fourier components are distributed in nodes. In each node, the block-tridiagonal matrix is inverted for each of allocated Fourier components. The algorithm for this second case has not yet been optimized. 10 refs., 4 figs

  5. A Miniature Recording Cardiotachometer

    DEFF Research Database (Denmark)

    Zsombor-Murray, Paul J; Vroomen, Louis J.; Hendriksen, Nils Thedin

    1981-01-01

    The design of a miniature, recording cardiotachometer is described. It is simple and can store digital data. Bench and field tests, using a hand-held display, are presented. Construction and principles of operation are discussed. Applications, with performing athlete subjects, are outlined....

  6. Miniature Optical Isolator, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — To address NASA's need for compact optical isolators, Physical Optics Corporation (POC) proposes to continue the development of a new Miniature Optical Isolator...

  7. Presynaptic inhibition of GABAergic synaptic transmission by adenosine in mouse hypothalamic hypocretin neurons.

    Science.gov (United States)

    Xia, J X; Xiong, J X; Wang, H K; Duan, S M; Ye, J N; Hu, Z A

    2012-01-10

    Hypocretin neurons in the lateral hypothalamus, a new wakefulness-promoting center, have been recently regarded as an important target involved in endogenous adenosine-regulating sleep homeostasis. The GABAergic synaptic transmissions are the main inhibitory afferents to hypocretin neurons, which play an important role in the regulation of excitability of these neurons. The inhibitory effect of adenosine, a homeostatic sleep-promoting factor, on the excitatory glutamatergic synaptic transmissions in hypocretin neurons has been well documented, whether adenosine also modulates these inhibitory GABAergic synaptic transmissions in these neurons has not been investigated. In this study, the effect of adenosine on inhibitory postsynaptic currents (IPSCs) in hypocretin neurons was examined by using perforated patch-clamp recordings in the acute hypothalamic slices. The findings demonstrated that adenosine suppressed the amplitude of evoked IPSCs in a dose-dependent manner, which was completely abolished by 8-cyclopentyltheophylline (CPT), a selective antagonist of adenosine A1 receptor but not adenosine A2 receptor antagonist 3,7-dimethyl-1-(2-propynyl) xanthine. A presynaptic origin was suggested as following: adenosine increased paired-pulse ratio as well as reduced GABAergic miniature IPSC frequency without affecting the miniature IPSC amplitude. Further findings demonstrated that when the frequency of electrical stimulation was raised to 10 Hz, but not 1 Hz, a time-dependent depression of evoked IPSC amplitude was detected in hypocretin neurons, which could be partially blocked by CPT. However, under a higher frequency at 100 Hz stimulation, CPT had no action on the depressed GABAergic synaptic transmission induced by such tetanic stimulation in these hypocretin neurons. These results suggest that endogenous adenosine generated under certain stronger activities of synaptic transmissions exerts an inhibitory effect on GABAergic synaptic transmission in hypocretin

  8. Continuous flow nitration in miniaturized devices

    Directory of Open Access Journals (Sweden)

    Amol A. Kulkarni

    2014-02-01

    Full Text Available This review highlights the state of the art in the field of continuous flow nitration with miniaturized devices. Although nitration has been one of the oldest and most important unit reactions, the advent of miniaturized devices has paved the way for new opportunities to reconsider the conventional approach for exothermic and selectivity sensitive nitration reactions. Four different approaches to flow nitration with microreactors are presented herein and discussed in view of their advantages, limitations and applicability of the information towards scale-up. Selected recent patents that disclose scale-up methodologies for continuous flow nitration are also briefly reviewed.

  9. Goniometry and Limb Girth in Miniature Dachshunds

    Directory of Open Access Journals (Sweden)

    Stephanie A. Thomovsky

    2016-01-01

    Full Text Available Purpose. To report the mean and median pelvic limb joint angles and girth measurements in miniature Dachshunds presenting with varying degrees of pelvic limb weakness secondary to thoracolumbar intervertebral disc extrusion. Methods. 15 miniature Dachshunds who presented to WSU-VTH for thoracolumbar disc extrusion. Dachshunds varied in neurologic status from ambulatory paraparetic to paraplegic at the time of measurements. Results. There were no significant differences in joint angles or girth among the three groups (ambulatory paraparetic, nonambulatory paraparetic, or paraplegic (P>0.05. When group was disregarded and values for extension, flexion, and girth combined, no differences existed. Conclusions. Goniometry and limb girth measurements can successfully be made in the miniature Dachshund; however, the shape of the Dachshund leg makes obtaining these values challenging. There were no differences in joint angle or girth measurements between dogs with varying neurologic dysfunction at the time of measurement.

  10. Goniometry and Limb Girth in Miniature Dachshunds.

    Science.gov (United States)

    Thomovsky, Stephanie A; Chen, Annie V; Kiszonas, Alecia M; Lutskas, Lori A

    2016-01-01

    Purpose. To report the mean and median pelvic limb joint angles and girth measurements in miniature Dachshunds presenting with varying degrees of pelvic limb weakness secondary to thoracolumbar intervertebral disc extrusion. Methods. 15 miniature Dachshunds who presented to WSU-VTH for thoracolumbar disc extrusion. Dachshunds varied in neurologic status from ambulatory paraparetic to paraplegic at the time of measurements. Results. There were no significant differences in joint angles or girth among the three groups (ambulatory paraparetic, nonambulatory paraparetic, or paraplegic) (P > 0.05). When group was disregarded and values for extension, flexion, and girth combined, no differences existed. Conclusions. Goniometry and limb girth measurements can successfully be made in the miniature Dachshund; however, the shape of the Dachshund leg makes obtaining these values challenging. There were no differences in joint angle or girth measurements between dogs with varying neurologic dysfunction at the time of measurement.

  11. Pricing of miniature vehicles made from telephone card waste

    Science.gov (United States)

    Puspitasari, N. B.; Pujotomo, D.; Muhardiansyah, H.

    2017-12-01

    The number of electronic devices in Indonesia in the last 10 years has been increasing quite drastically which contributes to more electronic waste. E-waste or electronic waste have different characteristics from other kinds of waste. Components of electronic waste often poisonous, consisting dangerous chemicals. The telephone card wasted is also an electronic waste. One alternative to handle and manage telephone card waste is to recycle it into collectible miniature vehicles. But the price of these miniatures is quite high, causing low interest in buying them. A research on the price of miniature vehicles in relation to consumers’ Ability to Pay (ATP) and Willingness to Pay (WTP) needs to be done. Segmentation analysis data, target, product positioning and product marketing mix are needed before commencing the research. Data collection is done through a survey by spreading questionnaire to 100 miniature vehicle collectors in Semarang, questioning their ability and willingness to pay recycled miniature vehicles. Calculations showed average ATP of Rp.112.520, 24 and average WTP of Rp.76.870. The last result showed the estimate pricing according to ATP and WTP which is Rp.66.000 with 58% of the respondents claiming to be willing and able to pay that price.

  12. Miniature UAVs : An overview

    NARCIS (Netherlands)

    Weimar, P.W.L.; Kerkkamp, J.S.F.; Wiel, R.A.N.; Meiller, P.P.; Bos, J.G.H.

    2014-01-01

    With this book TNO provides an overview of topics related to Miniature Unmanned Aerial Vehicles (MUAVs). Both novices and experts may find this publication valuable. The Netherlands Organisation for Applied Scientific Research TNO conducts research on UAVs and MUAVs, see for example [1], on the

  13. The Use of Patient-Specific Induced Pluripotent Stem Cells (iPSCs to Identify Osteoclast Defects in Rare Genetic Bone Disorders

    Directory of Open Access Journals (Sweden)

    I-Ping Chen

    2014-12-01

    Full Text Available More than 500 rare genetic bone disorders have been described, but for many of them only limited treatment options are available. Challenges for studying these bone diseases come from a lack of suitable animal models and unavailability of skeletal tissues for studies. Effectors for skeletal abnormalities of bone disorders may be abnormal bone formation directed by osteoblasts or anomalous bone resorption by osteoclasts, or both. Patient-specific induced pluripotent stem cells (iPSCs can be generated from somatic cells of various tissue sources and in theory can be differentiated into any desired cell type. However, successful differentiation of hiPSCs into functional bone cells is still a challenge. Our group focuses on the use of human iPSCs (hiPSCs to identify osteoclast defects in craniometaphyseal dysplasia. In this review, we describe the impact of stem cell technology on research for better treatment of such disorders, the generation of hiPSCs from patients with rare genetic bone disorders and current protocols for differentiating hiPSCs into osteoclasts.

  14. A performance study of sparse Cholesky factorization on INTEL iPSC/860

    Science.gov (United States)

    Zubair, M.; Ghose, M.

    1992-01-01

    The problem of Cholesky factorization of a sparse matrix has been very well investigated on sequential machines. A number of efficient codes exist for factorizing large unstructured sparse matrices. However, there is a lack of such efficient codes on parallel machines in general, and distributed machines in particular. Some of the issues that are critical to the implementation of sparse Cholesky factorization on a distributed memory parallel machine are ordering, partitioning and mapping, load balancing, and ordering of various tasks within a processor. Here, we focus on the effect of various partitioning schemes on the performance of sparse Cholesky factorization on the Intel iPSC/860. Also, a new partitioning heuristic for structured as well as unstructured sparse matrices is proposed, and its performance is compared with other schemes.

  15. Femtosecond laser-assisted cataract surgery and implantable miniature telescope

    Directory of Open Access Journals (Sweden)

    Randal Pham

    2017-09-01

    Conclusions and importance: To our knowledge and confirmed by the manufacturer of the implantable miniature telescope this is the first case ever reported of a patient who has undergone femtosecond laser cataract surgery with corneal astigmatism correction and implantation of the implantable miniature telescope. This is also the first case report of the preoperative use of microperimetry and visual electrophysiology to evaluate a patient's postoperative potential visual acuity. The success of the procedure illustrated the importance of meticulous preoperative planning, the combined use of state-of-the-art technologies and the seamless teamwork in order to achieve the best clinical outcome for patients who undergo implantation of the implantable miniature telescope.

  16. Gradual Changes of Gut Microbiota in Weaned Miniature Piglets

    Directory of Open Access Journals (Sweden)

    Xianghua Yan

    2016-11-01

    Full Text Available Colonization of gut microbiota in mammals during the early life is vital to host health. The miniature piglet has recently been considered as an optimal infant model. However, less is known about the development of gut microbiota in miniature piglets. Here, this study was conducted to explore how the gut microbiota develops in weaned Congjiang miniature piglets. In contrast to the relatively stabilized gut fungal community, gut bacterial community showed a marked drop in alpha diversity, accompanied by significant alterations in taxonomic compositions. The relative abundances of 24 bacterial genera significantly declined, whereas the relative abundances of 7 bacterial genera (Fibrobacter, Collinsella, Roseburia, Prevotella, Dorea, Howardella, and Blautia significantly increased with the age of weaned piglets. Fungal taxonomic analysis showed that the relative abundances of 2 genera (Kazachstania and Aureobasidium significantly decreased, whereas the relative abundances of 4 genera (Aspergillus, Cladosporium, Simplicillium, and Candida significantly increased as the piglets aged. Kazachstania telluris was the signature species predominated in gut fungal communities of weaned miniature piglets. The functional maturation of the gut bacterial community was characterized by the significantly increased digestive system, glycan biosynthesis and metabolism, and vitamin B biosynthesis as the piglets aged. These findings suggest that marked gut microbial changes in Congjiang miniature piglets may contribute to understand the potential gut microbiota development of weaned infants.

  17. Miniature, Single Channel, Memory-Based, High-G Acceleration Recorder (Millipen)

    International Nuclear Information System (INIS)

    Rohwer, Tedd A.

    1999-01-01

    The Instrumentation and Telemetry Departments at Sandia National Laboratories have been instrumenting earth penetrators for over thirty years. Recorded acceleration data is used to quantify penetrator performance. Penetrator testing has become more difficult as desired impact velocities have increased. This results in the need for small-scale test vehicles and miniature instrumentation. A miniature recorder will allow penetrator diameters to significantly decrease, opening the window of testable parameters. Full-scale test vehicles will also benefit from miniature recorders by using a less intrusive system to instrument internal arming, fusing, and firing components. This single channel concept is the latest design in an ongoing effort to miniaturize the size and reduce the power requirement of acceleration instrumentation. A micro-controller/memory based system provides the data acquisition, signal conditioning, power regulation, and data storage. This architecture allows the recorder, including both sensor and electronics, to occupy a volume of less than 1.5 cubic inches, draw less than 200mW of power, and record 15kHz data up to 40,000 gs. This paper will describe the development and operation of this miniature acceleration recorder

  18. Variable behavior of iPSCs derived from CML patients for response to TKI and hematopoietic differentiation.

    Directory of Open Access Journals (Sweden)

    Aurélie Bedel

    Full Text Available Chronic myeloid leukemia disease (CML found effective therapy by treating patients with tyrosine kinase inhibitors (TKI, which suppress the BCR-ABL1 oncogene activity. However, the majority of patients achieving remission with TKI still have molecular evidences of disease persistence. Various mechanisms have been proposed to explain the disease persistence and recurrence. One of the hypotheses is that the primitive leukemic stem cells (LSCs can survive in the presence of TKI. Understanding the mechanisms leading to TKI resistance of the LSCs in CML is a critical issue but is limited by availability of cells from patients. We generated induced pluripotent stem cells (iPSCs derived from CD34⁺ blood cells isolated from CML patients (CML-iPSCs as a model for studying LSCs survival in the presence of TKI and the mechanisms supporting TKI resistance. Interestingly, CML-iPSCs resisted to TKI treatment and their survival did not depend on BCR-ABL1, as for primitive LSCs. Induction of hematopoietic differentiation of CML-iPSC clones was reduced compared to normal clones. Hematopoietic progenitors obtained from iPSCs partially recovered TKI sensitivity. Notably, different CML-iPSCs obtained from the same CML patients were heterogeneous, in terms of BCR-ABL1 level and proliferation. Thus, several clones of CML-iPSCs are a powerful model to decipher all the mechanisms leading to LSC survival following TKI therapy and are a promising tool for testing new therapeutic agents.

  19. The Textile Elements in Ottoman Miniatures

    Directory of Open Access Journals (Sweden)

    Kevser Gürcan Y A R D I M C I

    2015-07-01

    Full Text Available With the value given to the art and the artist, high quality works of art in many fields were produced in the Ottoman Era. The art of weaving also lived its brightest period in terms of color, design, and weaving techniques in the Ottoman Empire in XVI. Ce ntury. The weaving products shaped the lifestyles of the people in those times and received great interest in the Palace as well. Silk woven fabrics had become such a great power in those times that it became the greatest symbol showing the power of the Ot toman Empire to the foreigners, and the determiner of the social standing within the society. The Ottoman Sultans used their clothing, which they made to become flamboyant with embroideries, to distinguish themselves from the public, and make them accept t heir power. Among the presents that were presented to the Sultans, clothes, kaftans, and similar fabrics as well as other precious presents, were frequent. The miniature manuscripts that were produced in the Palace are in the quality of unique documents t hat transfer yesterday’s knowledge to the modern age. It is easy to decode the dimensions of the clothing habits, decoration elements and hierarchy concepts of the Ottoman Era, as well as the weaving activities by using the miniature manuscripts. On the ot her hand, these elements constitute a rich alphabet in transferring the emotional structure of the society in those times, the traditions and habits to our world today. The greatest share in this effort belongs to the artists who depicted the miniatures by staying loyal to the texts in the manuscripts as well as to their active participation in the events of those times and their narrating the events as the very first observers. In addition, the muralists depicting the manuscripts and their undertaking the job of drawing the designs on the original fabric helped them to reflect the richness in the design of those times to the miniatures. In this study, the weavings and the accessories

  20. Miniaturized nuclear battery

    International Nuclear Information System (INIS)

    Adler, K.; Ducommun, G.

    1976-01-01

    The invention relates to a miniaturized nuclear battery, consisting of several in series connected cells, wherein each cell contains a support which acts as positive pole and which supports on one side a β-emitter, above said emitter is a radiation resisting insulation layer which is covered by an absorption layer, above which is a collector layer, and wherein the in series connected calls are disposed in an airtight case

  1. Variable recruitment in bundles of miniature pneumatic artificial muscles.

    Science.gov (United States)

    DeLaHunt, Sylvie A; Pillsbury, Thomas E; Wereley, Norman M

    2016-09-13

    The natural compliance and force generation properties of pneumatic artificial muscles (PAMs) allow them to operate like human muscles in anthropomorphic robotic manipulators. Traditionally, manipulators use a single PAM or multiple PAMs actuated in unison in place of a human muscle. However, these standard manipulators can experience significant efficiency losses when operated outside their target performance ranges at low actuation pressures. This study considers the application of a variable recruitment control strategy to a parallel bundle of miniature PAMs as an attempt to mimic the selective recruitment of motor units in a human muscle. Bundles of miniature PAMs are experimentally characterized, their actuation behavior is modeled, and the efficiency gains and losses associated with the application of a variable recruitment control strategy are assessed. This bio-inspired control strategy allows muscle bundles to operate the fewest miniature PAMs necessary to achieve a desired performance objective, improving the muscle bundle's operating efficiency over larger ranges of force generation and displacement. The study also highlights the need for improved PAM fabrication techniques to facilitate the production of identical miniature PAMs for inclusion in muscle bundles.

  2. Generation of iPSC line iPSC-FH2.1 in hypoxic conditions from human foreskin fibroblasts

    Directory of Open Access Journals (Sweden)

    María Questa

    2016-03-01

    Full Text Available Human foreskin fibroblasts were used to generate the iPSC line iPSC-FH2.1 using the EF1a-hSTEMCCA-loxP vector expressing OCT4, SOX2, c-MYC and KLF4, in 5% O2 culture conditions. Stemness was confirmed, as was pluripotency both in vivo and in vitro, in normoxia and hypoxia. Human Embryonic Stem Cell (hESC line WA-09 and reprogrammed fibroblast primary culture HFF-FM were used as controls.

  3. Miniature Blimps for Surveillance and Collection of Samples

    Science.gov (United States)

    Jones, Jack

    2004-01-01

    Miniature blimps are under development as robots for use in exploring the thick, cold, nitrogen atmosphere of Saturn's moon, Titan. Similar blimps can also be used for surveillance and collection of biochemical samples in buildings, caves, subways, and other, similar structures on Earth. The widely perceived need for means to thwart attacks on buildings and to mitigate the effects of such attacks has prompted consideration of the use of robots. Relative to rover-type (wheeled) robots that have been considered for such uses, miniature blimps offer the advantage of ability to move through the air in any direction and, hence, to perform tasks that are difficult or impossible for wheeled robots, including climbing stairs and looking through windows. In addition, miniature blimps are expected to have greater range and to cost less, relative to wheeled robots.

  4. Miniature scientific-grade induction magnetometer for cubesats

    Science.gov (United States)

    Pronenko, Vira

    2017-04-01

    One of the main areas of space research is the study and forecasting of space weather. The society is more and more depending nowadays on satellite technology and communications, so it is vital to understand the physical process in the solar-terrestrial system which may disturb them. Besides the solar radiation and Space Weather effects, the Earth's ionosphere is also modified by the ever increasing industrial activity. There have been also multiple reports relating VLF and ELF wave activity to atmospheric storms and geological processes, such as earthquakes and volcanic activity. For advancing in these fields, the AC magnetic field permanent monitoring is crucial. Using the cubesat technology would allow increasing the number of measuring points dramatically. It is necessary to mention that the cubesats use for scientific research requires the miniaturization of scientific sensors what is a serious problem because the reduction of their dimensions leads, as a rule, to the parameters degradation, especially of sensitivity threshold. Today, there is no basic model of a sensitive miniature induction magnetometer. Even the smallest one of the known - for the Bepi-Colombo mission to Mercury - is too big for cubesats. The goal of the present report is to introduce the new design of miniature three-component sensor for measurement of alternative vector magnetic fields - induction magnetometer (IM). The study directions were concentrated on the ways and possibilities to create the miniature magnetometer with best combination of parameters. For this a set of scientific and technological problems, mostly aimed at the sensor construction improvement, was solved. The most important parameter characterizing magnetometer quality is its own magnetic noise level (NL). The analysis of the NL influencing factors is made and the ways to decrease it are discussed in the report. Finally, the LEMI-151 IM was developed for the SEAM cubesat mission with optimal performances within the

  5. Miniature Ground Mapping LADAR, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — System & Processes Engineering Corporation (SPEC) proposes a miniature solid state surface imaging LADAR, for imaging the landing areas providing precision...

  6. Miniature Pulpotomy of Symptomatic Mature Permanent Teeth: A Report of Two Cases.

    Science.gov (United States)

    Asgary, Saeed; Nourzadeh, Mahdieh; Eghbal, Mohammad Jafar

    2016-01-01

    Human dental pulp inflammation can progress to periapical lesion formation and conventional root canal treatment (RCT) has been the traditional method for disease management. This observational study presents two cases of vital pulp therapy in mature molars diagnosed with irreversible pulpitis and associated with apical periodontitis. In these two clinical cases, the involved teeth had deep carious lesions with a history of spontaneous/lingering pain and radiographic examinations revealed the presence of apical radiolucencies. A conservative miniature pulpotomy (MP) using calcium-enriched mixture (CEM) was performed and the teeth were permanently restored with amalgam. Clinical evaluations indicated resolution of pain 24 hours after treatment; the teeth showed normal vitality, remained asymptomatic and maintained normal function after recall examinations. Furthermore, the 18-month radiographic evaluation showed healing of the apical lesions. Vital pulp therapy using the MP technique with CEM appeared successful in avoiding RCT intervention. These two reports of case outcome suggest that simple MP using a CEM bioregenerative technique may provide a favorable outcome for permanent teeth diagnosed with irreversible pulpitis and associated with apical periodontitis.

  7. Autonomous stair-climbing with miniature jumping robots.

    Science.gov (United States)

    Stoeter, Sascha A; Papanikolopoulos, Nikolaos

    2005-04-01

    The problem of vision-guided control of miniature mobile robots is investigated. Untethered mobile robots with small physical dimensions of around 10 cm or less do not permit powerful onboard computers because of size and power constraints. These challenges have, in the past, reduced the functionality of such devices to that of a complex remote control vehicle with fancy sensors. With the help of a computationally more powerful entity such as a larger companion robot, the control loop can be closed. Using the miniature robot's video transmission or that of an observer to localize it in the world, control commands can be computed and relayed to the inept robot. The result is a system that exhibits autonomous capabilities. The framework presented here solves the problem of climbing stairs with the miniature Scout robot. The robot's unique locomotion mode, the jump, is employed to hop one step at a time. Methods for externally tracking the Scout are developed. A large number of real-world experiments are conducted and the results discussed.

  8. Impaired action potential initiation in GABAergic interneurons causes hyperexcitable networks in an epileptic mouse model carrying a human Na(V)1.1 mutation.

    Science.gov (United States)

    Hedrich, Ulrike B S; Liautard, Camille; Kirschenbaum, Daniel; Pofahl, Martin; Lavigne, Jennifer; Liu, Yuanyuan; Theiss, Stephan; Slotta, Johannes; Escayg, Andrew; Dihné, Marcel; Beck, Heinz; Mantegazza, Massimo; Lerche, Holger

    2014-11-05

    Mutations in SCN1A and other ion channel genes can cause different epileptic phenotypes, but the precise mechanisms underlying the development of hyperexcitable networks are largely unknown. Here, we present a multisystem analysis of an SCN1A mouse model carrying the NaV1.1-R1648H mutation, which causes febrile seizures and epilepsy in humans. We found a ubiquitous hypoexcitability of interneurons in thalamus, cortex, and hippocampus, without detectable changes in excitatory neurons. Interestingly, somatic Na(+) channels in interneurons and persistent Na(+) currents were not significantly changed. Instead, the key mechanism of interneuron dysfunction was a deficit of action potential initiation at the axon initial segment that was identified by analyzing action potential firing. This deficit increased with the duration of firing periods, suggesting that increased slow inactivation, as recorded for recombinant mutated channels, could play an important role. The deficit in interneuron firing caused reduced action potential-driven inhibition of excitatory neurons as revealed by less frequent spontaneous but not miniature IPSCs. Multiple approaches indicated increased spontaneous thalamocortical and hippocampal network activity in mutant mice, as follows: (1) more synchronous and higher-frequency firing was recorded in primary neuronal cultures plated on multielectrode arrays; (2) thalamocortical slices examined by field potential recordings revealed spontaneous activities and pathological high-frequency oscillations; and (3) multineuron Ca(2+) imaging in hippocampal slices showed increased spontaneous neuronal activity. Thus, an interneuron-specific generalized defect in action potential initiation causes multisystem disinhibition and network hyperexcitability, which can well explain the occurrence of seizures in the studied mouse model and in patients carrying this mutation. Copyright © 2014 the authors 0270-6474/14/3414874-16$15.00/0.

  9. Central Hypothyroidism in Miniature Schnauzers

    NARCIS (Netherlands)

    Voorbij, Annemarie M W Y; Leegwater, Peter A J; Buijtels, Jenny J C W M; Daminet, Sylvie; Kooistra, Hans S

    2016-01-01

    BACKGROUND: Primary hypothyroidism is a common endocrinopathy in dogs. In contrast, central hypothyroidism is rare in this species. OBJECTIVES: The objective of this article is to describe the occurrence and clinical presentation of central hypothyroidism in Miniature Schnauzers. Additionally, the

  10. Small is beautiful: features of the smallest insects and limits to miniaturization.

    Science.gov (United States)

    Polilov, Alexey A

    2015-01-07

    Miniaturization leads to considerable reorganization of structures in insects, affecting almost all organs and tissues. In the smallest insects, comparable in size to unicellular organisms, modifications arise not only at the level of organs, but also at the cellular level. Miniaturization is accompanied by allometric changes in many organ systems. The consequences of miniaturization displayed by different insect taxa include both common and unique changes. Because the smallest insects are among the smallest metazoans and have the most complex organization among organisms of the same size, their peculiar structural features and the factors that limit their miniaturization are of considerable theoretical interest to general biology.

  11. Structure Design and Performance Analysis of High-Speed Miniature Ball Bearing

    Science.gov (United States)

    Li, Songsheng; Zhang, Guoye; Chen, Bin; Shen, Yuan

    2017-07-01

    The working performances of miniature ball bearings are obviously affected by its’ geometric structure parameters. In this paper, quasi-static analysis theory is applied in the design of miniature ball bearings. Firstly, it is studied the influence of geometry structure, preload and rotating speed on the dynamic performance of bearing. Secondly, bearing dynamic characteristics are analyzed which include the bearing stiffness and Spin to roll Ratio. Lastly, the contact stress and bearing life are calculated. The results indicate that structure parameters play an importance role in bearing’s dynamic performances. Miniature ball bearings which have lager ball number, bigger ball diameter and smaller inner race groove radius can get better performances while velocity and preload have great impact on the bearing life. So that parameters of miniature bearing should be chosen cautiously.

  12. Using Miniature Landforms in Teaching Geomorphology.

    Science.gov (United States)

    Petersen, James F.

    1986-01-01

    This paper explores the uses of true landform miniatures and small-scale analogues and suggests ways to teach geomorphological concepts using small-scale relief features as illustrative examples. (JDH)

  13. Miniaturization of Multiple-Layer Folded Patch Antennas

    DEFF Research Database (Denmark)

    Zhang, Jiaying; Breinbjerg, Olav

    2009-01-01

    A new folded patch antenna with multiple layers was developed in this paper, by folding the patch in a proper way, and a highly miniaturized antenna can be realized. The multiple layer patch with 4-layer and 6-layer are designed and evaluated at 2.4 GHz, 915 MHz, and 415 MHz respectively. Then a 4...... layer patch is fabricated and measured to validate the design method. The theoretical analysis, design and simulations, fabrications, as well as the measurements are presented in this paper. All the results show that the folded patch antenna is a good candidate in making a highly miniaturized compact...

  14. Use of miniature tensile specimen and video extensometer for measurement of mechanical properties

    International Nuclear Information System (INIS)

    Kumar, Kundan; Pooleery, Arun; Madhusoodanan, K.

    2014-08-01

    Miniaturisation of the tensile test specimen below the sub-size level poses various challenges, such as conformity of specimen to various acceptance criteria as per standard test specimen, aspect ratio, minimum number of grains required in a gauge cross-section, fabrication for uniformity in metrological values, etc. Apart from these, measurement of strain over a very limited available space on the test specimen is another practical challenge. Despite these limitations, miniature specimen testing is increasingly being used worldwide these days. The driving forces behind increasing use of miniature test techniques are new material development, assuring fitness of component after in-service-inspection, low dose of radiation exposure due to smaller dimensions of test specimens etc. However, the evaluation of mechanical properties from a miniature tensile test has a greater advantage over the other miniature novel test techniques, such as small punch test, ABI, miniature fatigue and impact tests etc., as it is a direct method of measurement of mechanical properties. This report covers various aspects of miniature tensile test methodologies, which include geometrical design of specimen having gauge length of 3-5 mm, fabrication, development of special fixtures for gripping the test specimens, and use of optical method for strain measurement. The geometrical design of the specimen and its behaviour over application of tensile load has been established using FEM analysis. A good agreement between conventional and miniature test results exemplifies the potential of the miniature tensile test technique. (author)

  15. Preface Miniaturization and Mass Spectrometry

    NARCIS (Netherlands)

    Unknown, [Unknown; le Gac, Severine; le Gac, S.; van den Berg, Albert; van den Berg, A.

    2009-01-01

    Miniaturization and Mass Spectrometry illustrates this trend and focuses on one particular analysis technique, mass spectrometry whose popularity has "dramatically" increased in the last two decades with the explosion of the field of biological analysis and the development of two "soft" ionization

  16. Modelling neurodegenerative diseases in vitro: Recent advances in 3D iPSC technologies

    Directory of Open Access Journals (Sweden)

    Elodie J Siney

    2018-03-01

    Full Text Available The discovery of induced pluripotent stem cells (iPSC 12 years ago has fostered the development of innovative patient-derived in vitro models for better understanding of disease mechanisms. This is particularly relevant to neurodegenerative diseases, where availability of live human brain tissue for research is limited and post-mortem interval changes influence readouts from autopsy-derived human tissue. Hundreds of iPSC lines have now been prepared and banked, thanks to several large scale initiatives and cell banks. Patient- or engineered iPSC-derived neural models are now being used to recapitulate cellular and molecular aspects of a variety of neurodegenerative diseases, including early and pre-clinical disease stages. The broad relevance of these models derives from the availability of a variety of differentiation protocols to generate disease-specific cell types and the manipulation to either introduce or correct disease-relevant genetic modifications. Moreover, the use of chemical and physical three-dimensional (3D matrices improves control over the extracellular environment and cellular organization of the models. These iPSC-derived neural models can be utilised to identify target proteins and, importantly, provide high-throughput screening for drug discovery. Choosing Alzheimer’s disease (AD as an example, this review describes 3D iPSC-derived neural models and their advantages and limitations. There is now a requirement to fully characterise and validate these 3D iPSC-derived neural models as a viable research tool that is capable of complementing animal models of neurodegeneration and live human brain tissue. With further optimization of differentiation, maturation and aging protocols, as well as the 3D cellular organisation and extracellular matrix to recapitulate more closely, the molecular extracellular-environment of the human brain, 3D iPSC-derived models have the potential to deliver new knowledge, enable discovery of novel

  17. Miniaturized inertial impactor for personal airborne particulate monitoring: Prototyping

    Science.gov (United States)

    Pasini, Silvia; Bianchi, Elena; Dubini, Gabriele; Cortelezzi, Luca

    2017-11-01

    Computational fluid dynamic (CFD) simulations allowed us to conceive and design a miniaturized inertial impactor able to collect fine airborne particulate matter (PM10, PM2.5 and PM1). We created, by 3D printing, a prototype of the impactor. We first performed a set of experiments by applying a suction pump to the outlets and sampling the airborne particulate of our laboratory. The analysis of the slide showed a collection of a large number of particles, spanning a wide range of sizes, organized in a narrow band located below the exit of the nozzle. In order to show that our miniaturized inertial impactor can be truly used as a personal air-quality monitor, we performed a second set of experiments where the suction needed to produce the airflow through the impactor is generated by a human being inhaling through the outlets of the prototype. To guarantee a number of particles sufficient to perform a quantitative characterization, we collected particles performing ten consecutive deep inhalations. Finally, the potentiality for realistic applications of our miniaturized inertial impactor used in combination with a miniaturized single-particle detector will be discussed. CARIPLO Fundation - project MINUTE (Grant No. 2011-2118).

  18. Spontaneous mutation by mutagenic repair of spontaneous lesions in DNA

    International Nuclear Information System (INIS)

    Hastings, P.J.; Quah, S.-K.; Borstel, R.C. von

    1976-01-01

    It is stated that strains of yeast carrying mutations in many of the steps in pathways repairing radiation-induced damage to DNA have enhanced spontaneous mutation rates. Most strains isolated because they have enhanced spontaneous mutation carry mutations in DNA repair systems. This suggests that much spontaneous mutation arises by mutagenic repair of spontaneous lesions. (author)

  19. 46 CFR 52.25-5 - Miniature boilers (modifies PMB-1 through PMB-21).

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Miniature boilers (modifies PMB-1 through PMB-21). 52.25... ENGINEERING POWER BOILERS Other Boiler Types § 52.25-5 Miniature boilers (modifies PMB-1 through PMB-21). Miniature boilers must meet the applicable provisions in this part for the boiler type involved and the...

  20. Development of fatigue life evaluation technique using miniature specimen

    International Nuclear Information System (INIS)

    Nogami, Shuhei; Nishimura, Arata; Fujiwara, Masaharu; Hisaka, Tomoaki

    2012-01-01

    To develop the fatigue life evaluation technique using miniature specimen, the investigation of the effect of specimen size and specimen shape on the fatigue life and the development of the fatigue testing machine, especially the extensometer, were carried out. The effect of specimen size on the fatigue life was almost negligible for the round-bar specimens. The shorter fatigue life at relatively low strain range conditions for the hourglass specimen that the standard specimen were observed. Therefore the miniature round-bar specimen was considered to be adequate for the fatigue life evaluation using small specimen. Several types of the extensometer system using a strain gauge and a laser has been developed for realizing the fatigue test of the miniature round-bar specimen at high temperature in vacuum. (author)

  1. Glomerular Lesions in Proteinuric Miniature Schnauzer Dogs.

    Science.gov (United States)

    Furrow, E; Lees, G E; Brown, C A; Cianciolo, R E

    2017-05-01

    Miniature Schnauzer dogs are predisposed to idiopathic hypertriglyerceridemia, which increases risk for diseases such as pancreatitis and gallbladder mucocele. Recently, elevated triglyceride concentrations have been associated with proteinuria in this breed, although it is difficult to determine which abnormality is primary. Retrospective review of renal tissue from 27 proteinuric Miniature Schnauzers revealed that 20 dogs had ultrastructural evidence of osmophilic globules consistent with lipid in glomerular tufts. Seven of these dogs had lipid thromboemboli in glomerular capillary loops that distorted their shape and compressed circulating erythrocytes. Triglyceride concentrations were reported in 6 of these 7 dogs, and all were hypertriglyceridemic. In addition, glomerular lipidosis (defined as accumulation of foam cells within peripheral capillary loops) was identified in a single dog. The remaining 12 dogs had smaller amounts of lipid that could only be identified ultrastructurally. Neither signalment data nor clinicopathologic parameters (serum albumin, serum creatinine, urine protein-to-creatinine ratio, and blood pressure) differed among the various types of lipid lesions. During the time course of this study, all dogs diagnosed with glomerular lipid thromboemboli were Miniature Schnauzers, underscoring the importance of recognizing these clear spaces within capillary loops as lipid.

  2. Miniature tensile test specimens for fusion reactor irradiation studies

    International Nuclear Information System (INIS)

    Klueh, R.L.

    1985-01-01

    Three miniature sheet-type tensile specimens and a miniature rod-type specimen are being used to determine irradiated tensile properties for alloy development for fusion reactors. The tensile properties of type 316 stainless steel were determined with these different specimens, and the results were compared. Reasonably good agreement was observed. However, there were differences that led to recommendations on which specimens are preferred. 4 references, 9 figures, 6 tables

  3. Analysis of nonlinear elastic behavior in miniature pneumatic artificial muscles

    Science.gov (United States)

    Hocking, Erica G.; Wereley, Norman M.

    2013-01-01

    Pneumatic artificial muscles (PAMs) are well known for their excellent actuator characteristics, including high specific work, specific power, and power density. Recent research has focused on miniaturizing this pneumatic actuator technology in order to develop PAMs for use in small-scale mechanical systems, such as those found in robotic or aerospace applications. The first step in implementing these miniature PAMs was to design and characterize the actuator. To that end, this study presents the manufacturing process, experimental characterization, and analytical modeling of PAMs with millimeter-scale diameters. A fabrication method was developed to consistently produce low-cost, high performance, miniature PAMs using commercially available materials. The quasi-static behavior of these PAMs was determined through experimentation on a single actuator with an active length of 39.16 mm (1.54 in) and a diameter of 4.13 mm (0.1625 in). Testing revealed the PAM’s full evolution of force with displacement for operating pressures ranging from 207 to 552 kPa (30-80 psi in 10 psi increments), as well as the blocked force and free contraction at each pressure. Three key nonlinear phenomena were observed: nonlinear PAM stiffness, hysteresis of the force versus displacement response for a given pressure, and a pressure deadband. To address the analysis of the nonlinear response of these miniature PAMs, a nonlinear stress versus strain model, a hysteresis model, and a pressure bias are introduced into a previously developed force balance analysis. Parameters of these nonlinear model refinements are identified from the measured force versus displacement data. This improved nonlinear force balance model is shown to capture the full actuation behavior of the miniature PAMs at each operating pressure and reconstruct miniature PAM response with much more accuracy than previously possible.

  4. Analysis of nonlinear elastic behavior in miniature pneumatic artificial muscles

    International Nuclear Information System (INIS)

    Hocking, Erica G; Wereley, Norman M

    2013-01-01

    Pneumatic artificial muscles (PAMs) are well known for their excellent actuator characteristics, including high specific work, specific power, and power density. Recent research has focused on miniaturizing this pneumatic actuator technology in order to develop PAMs for use in small-scale mechanical systems, such as those found in robotic or aerospace applications. The first step in implementing these miniature PAMs was to design and characterize the actuator. To that end, this study presents the manufacturing process, experimental characterization, and analytical modeling of PAMs with millimeter-scale diameters. A fabrication method was developed to consistently produce low-cost, high performance, miniature PAMs using commercially available materials. The quasi-static behavior of these PAMs was determined through experimentation on a single actuator with an active length of 39.16 mm (1.54 in) and a diameter of 4.13 mm (0.1625 in). Testing revealed the PAM’s full evolution of force with displacement for operating pressures ranging from 207 to 552 kPa (30–80 psi in 10 psi increments), as well as the blocked force and free contraction at each pressure. Three key nonlinear phenomena were observed: nonlinear PAM stiffness, hysteresis of the force versus displacement response for a given pressure, and a pressure deadband. To address the analysis of the nonlinear response of these miniature PAMs, a nonlinear stress versus strain model, a hysteresis model, and a pressure bias are introduced into a previously developed force balance analysis. Parameters of these nonlinear model refinements are identified from the measured force versus displacement data. This improved nonlinear force balance model is shown to capture the full actuation behavior of the miniature PAMs at each operating pressure and reconstruct miniature PAM response with much more accuracy than previously possible. (paper)

  5. Miniature bread baking as a timesaving research approach and mathematical modeling of browning kinetics

    NARCIS (Netherlands)

    Zhang, Lu; Putranto, Aditya; Zhou, Weibiao; Boom, Remko M.; Schutyser, Maarten A.I.; Chen, Xiao Dong

    2016-01-01

    Miniature bread baking is presented as an economical and timesaving laboratory approach to study the baking process in the present work. Results indicate that the miniature bread baking is essentially analogical to the baking process of regular-sized bread: quality-related properties of miniature

  6. Lymphoblast-derived integration-free iPSC line AD-TREM2-1 from a 67 year-old Alzheimer's disease patient expressing the TREM2 p.R47H variant

    Directory of Open Access Journals (Sweden)

    Soraia Martins

    2018-05-01

    Full Text Available Human lymphoblast cells from a male diagnosed with Alzheimer's disease (AD expressing the TREM2 p.R47H variant were used to generate integration-free induced pluripotent stem cells (iPSCs by over-expressing episomal-based plasmids harbouring OCT4, SOX2, NANOG, LIN28, c-MYC and L-MYC. AD-TREM2–1 was defined as pluripotent based on (i expression of pluripotency-associated markers (ii embryoid body-based differentiation into cell types representative of the three germ layers and (iii the similarity between the transcriptome of the iPSC line and the human embryonic stem cell line H1 with a Pearson correlation of 0.947.

  7. Generation of a human iPSC line from a patient with congenital glaucoma caused by mutation in CYP1B1 gene

    Directory of Open Access Journals (Sweden)

    Arantxa Bolinches-Amorós

    2018-04-01

    Full Text Available The human iPSC cell line, GLC-FiPS4F1 (ESi047-A, derived from dermal fibroblast from the patient with congenital glaucoma caused by the mutation of the gene CYP1B1, was generated by non-integrative reprogramming technology using OCT3/4, SOX2, CMYC and KLF4 reprogramming factors.

  8. Miniaturization design and implementation of magnetic field coupled RFID antenna

    Science.gov (United States)

    Hu, Tiling

    2013-03-01

    The development of internet of things has brought new opportunities and challenges to the application of RFID tags. Moreover, the Miniaturization application trend of tags at present has become the mainstream of development. In this paper, the double-layer design is to reduce the size of HF antenna, and the magnetic null point of magnetic reconnection region between the RLC resonant circuit and the reader provides sufficient energy to the miniaturization of antenna. The calculated and experimental results show that the miniaturization of HF antennas can meet the reading and writing requirement of the international standard ISO/IEC14443 standard. The results of this paper may make a positive contribution to the applications of RFID technology.

  9. Evaluation of the cationic trypsinogen gene for potential mutations in miniature schnauzers with pancreatitis.

    Science.gov (United States)

    Bishop, Micah A; Steiner, Jörg M; Moore, Lisa E; Williams, David A

    2004-10-01

    The purpose of this study was to evaluate the cationic trypsinogen gene in miniature schnauzers for possible mutations. Genetic mutations have been linked with hereditary pancreatitis in humans. Four miniature schnauzers were selected on the basis of a clinical history of pancreatitis. One healthy miniature schnauzer and 1 healthy mixed breed canine were enrolled as controls. DNA was extracted from these canines using a commercial kit. Primers were designed to amplify the entire canine cationic trypsinogen cDNA sequence. A polymerase chain reaction (PCR) was performed and products were purified and sequenced. All sequences were then compared. The healthy control canine, a healthy miniature schnauzer, and the 4 miniature schnauzers with pancreatitis showed identical sequences of the cationic trypsinogen gene to the published sequence. We conclude that, in contrast to humans with hereditary pancreatitis, mutations of the cationic trypsinogen gene do not play a major role in the genesis of pancreatitis in the miniature schnauzer.

  10. Motor Training Promotes Both Synaptic and Intrinsic Plasticity of Layer II/III Pyramidal Neurons in the Primary Motor Cortex.

    Science.gov (United States)

    Kida, Hiroyuki; Tsuda, Yasumasa; Ito, Nana; Yamamoto, Yui; Owada, Yuji; Kamiya, Yoshinori; Mitsushima, Dai

    2016-08-01

    Motor skill training induces structural plasticity at dendritic spines in the primary motor cortex (M1). To further analyze both synaptic and intrinsic plasticity in the layer II/III area of M1, we subjected rats to a rotor rod test and then prepared acute brain slices. Motor skill consistently improved within 2 days of training. Voltage clamp analysis showed significantly higher α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartate (AMPA/NMDA) ratios and miniature EPSC amplitudes in 1-day trained rats compared with untrained rats, suggesting increased postsynaptic AMPA receptors in the early phase of motor learning. Compared with untrained controls, 2-days trained rats showed significantly higher miniature EPSC amplitude and frequency. Paired-pulse analysis further demonstrated lower rates in 2-days trained rats, suggesting increased presynaptic glutamate release during the late phase of learning. One-day trained rats showed decreased miniature IPSC frequency and increased paired-pulse analysis of evoked IPSC, suggesting a transient decrease in presynaptic γ-aminobutyric acid (GABA) release. Moreover, current clamp analysis revealed lower resting membrane potential, higher spike threshold, and deeper afterhyperpolarization in 1-day trained rats-while 2-days trained rats showed higher membrane potential, suggesting dynamic changes in intrinsic properties. Our present results indicate dynamic changes in glutamatergic, GABAergic, and intrinsic plasticity in M1 layer II/III neurons after the motor training. © The Author 2016. Published by Oxford University Press.

  11. Laser direct marking applied to rasterizing miniature Data Matrix Code on aluminum alloy

    Science.gov (United States)

    Li, Xia-Shuang; He, Wei-Ping; Lei, Lei; Wang, Jian; Guo, Gai-Fang; Zhang, Teng-Yun; Yue, Ting

    2016-03-01

    Precise miniaturization of 2D Data Matrix (DM) Codes on Aluminum alloy formed by raster mode laser direct part marking is demonstrated. The characteristic edge over-burn effects, which render vector mode laser direct part marking inadequate for producing precise and readable miniature codes, are minimized with raster mode laser marking. To obtain the control mechanism for the contrast and print growth of miniature DM code by raster laser marking process, the temperature field model of long pulse laser interaction with material is established. From the experimental results, laser average power and Q frequency have an important effect on the contrast and print growth of miniature DM code, and the threshold of laser average power and Q frequency for an identifiable miniature DM code are respectively 3.6 W and 110 kHz, which matches the model well within normal operating conditions. In addition, the empirical model of correlation occurring between laser marking parameters and module size is also obtained, and the optimal processing parameter values for an identifiable miniature DM code of different but certain data size are given. It is also found that an increase of the repeat scanning number effectively improves the surface finish of bore, the appearance consistency of modules, which has benefit to reading. The reading quality of miniature DM code is greatly improved using ultrasonic cleaning in water by avoiding the interference of color speckles surrounding modules.

  12. Scalable 96-well Plate Based iPSC Culture and Production Using a Robotic Liquid Handling System.

    Science.gov (United States)

    Conway, Michael K; Gerger, Michael J; Balay, Erin E; O'Connell, Rachel; Hanson, Seth; Daily, Neil J; Wakatsuki, Tetsuro

    2015-05-14

    Continued advancement in pluripotent stem cell culture is closing the gap between bench and bedside for using these cells in regenerative medicine, drug discovery and safety testing. In order to produce stem cell derived biopharmaceutics and cells for tissue engineering and transplantation, a cost-effective cell-manufacturing technology is essential. Maintenance of pluripotency and stable performance of cells in downstream applications (e.g., cell differentiation) over time is paramount to large scale cell production. Yet that can be difficult to achieve especially if cells are cultured manually where the operator can introduce significant variability as well as be prohibitively expensive to scale-up. To enable high-throughput, large-scale stem cell production and remove operator influence novel stem cell culture protocols using a bench-top multi-channel liquid handling robot were developed that require minimal technician involvement or experience. With these protocols human induced pluripotent stem cells (iPSCs) were cultured in feeder-free conditions directly from a frozen stock and maintained in 96-well plates. Depending on cell line and desired scale-up rate, the operator can easily determine when to passage based on a series of images showing the optimal colony densities for splitting. Then the necessary reagents are prepared to perform a colony split to new plates without a centrifugation step. After 20 passages (~3 months), two iPSC lines maintained stable karyotypes, expressed stem cell markers, and differentiated into cardiomyocytes with high efficiency. The system can perform subsequent high-throughput screening of new differentiation protocols or genetic manipulation designed for 96-well plates. This technology will reduce the labor and technical burden to produce large numbers of identical stem cells for a myriad of applications.

  13. C/EBPα creates elite cells for iPSC reprogramming by upregulating Klf4 and increasing the levels of Lsd1 and Brd4

    DEFF Research Database (Denmark)

    Di Stefano, Bruno; Collombet, Samuel; Jakobsen, Janus Schou

    2016-01-01

    reprogrammed into iPSCs by the Yamanaka factors OSKM. Here we show that C/EBPα post-transcriptionally increases the abundance of several hundred proteins, including Lsd1, Hdac1, Brd4, Med1 and Cdk9, components of chromatin-modifying complexes present at super-enhancers. Lsd1 was found to be required for B cell...

  14. MiR-25 regulates Wwp2 and Fbxw7 and promotes reprogramming of mouse fibroblast cells to iPSCs.

    Directory of Open Access Journals (Sweden)

    Dong Lu

    Full Text Available miRNAs are a class of small non-coding RNAs that regulate gene expression and have critical functions in various biological processes. Hundreds of miRNAs have been identified in mammalian genomes but only a small number of them have been functionally characterized. Recent studies also demonstrate that some miRNAs have important roles in reprogramming somatic cells to induced pluripotent stem cells (iPSCs.We screened 52 miRNAs cloned in a piggybac (PB vector for their roles in reprogramming of mouse embryonic fibroblast cells to iPSCs. To identify targets of miRNAs, we made Dgcr8-deficient embryonic stem (ES cells and introduced miRNA mimics to these cells, which lack miRNA biogenesis. The direct target genes of miRNA were identified through global gene expression analysis and target validation.We found that over-expressing miR-25 or introducing miR-25 mimics enhanced production of iPSCs. We identified a number of miR-25 candidate gene targets. Of particular interest were two ubiquitin ligases, Wwp2 and Fbxw7, which have been proposed to regulate Oct4, c-Myc and Klf5, respectively. Our findings thus highlight the complex interplay between miRNAs and transcription factors involved in reprogramming, stem cell self-renewal and maintenance of pluripotency.

  15. Dissecting the Contributions of Cooperating Gene Mutations to Cancer Phenotypes and Drug Responses with Patient-Derived iPSCs

    Directory of Open Access Journals (Sweden)

    Chan-Jung Chang

    2018-05-01

    Full Text Available Summary: Connecting specific cancer genotypes with phenotypes and drug responses constitutes the central premise of precision oncology but is hindered by the genetic complexity and heterogeneity of primary cancer cells. Here, we use patient-derived induced pluripotent stem cells (iPSCs and CRISPR/Cas9 genome editing to dissect the individual contributions of two recurrent genetic lesions, the splicing factor SRSF2 P95L mutation and the chromosome 7q deletion, to the development of myeloid malignancy. Using a comprehensive panel of isogenic iPSCs—with none, one, or both genetic lesions—we characterize their relative phenotypic contributions and identify drug sensitivities specific to each one through a candidate drug approach and an unbiased large-scale small-molecule screen. To facilitate drug testing and discovery, we also derive SRSF2-mutant and isogenic normal expandable hematopoietic progenitor cells. We thus describe here an approach to dissect the individual effects of two cooperating mutations to clinically relevant features of malignant diseases. : Papapetrou and colleagues develop a comprehensive panel of isogenic iPSC lines with SRSF2 P95L mutation and chr7q deletion. They use these cells to identify cellular phenotypes contributed by each genetic lesion and therapeutic vulnerabilities specific to each one and develop expandable hematopoietic progenitor cell lines to facilitate drug discovery. Keywords: induced pluripotent stem cells, myelodysplastic syndrome, CRISPR/Cas9, gene editing, mutational cooperation, splicing factor mutations, spliceosomal mutations, SRSF2, chr7q deletion

  16. Aesthetics of Islamic Miniature Art During the Periods of Safavid and ...

    African Journals Online (AJOL)

    Islamic art represents the spiritual and physical aspects in the lives of Muslims. Meaningful beauty in Islamic art expresses Islamic aesthetics. Islamic aesthetics is the connection between beauty and the sacred. The article is devoted to the Islamic art and miniature paintings of Timurid and Safavid periods in Iran. Miniature ...

  17. Airtight miniaturized chromatography: a safer method for radiopharmaceutical quality control

    International Nuclear Information System (INIS)

    Coupal, J.J.; Shih, W.J.; Ryo, U.Y.

    1988-01-01

    Miniaturized chromatography is widely used for quality control of radiopharmaceuticals. Recently, published chromatography procedures have illustrated or described chromatography chambers open to the air in use, suggesting that volatile toxic mobile phases are harmless to people in the vicinity. The authors describe the results of their search for an inexpensive closed chromatography chamber that can be used to derive safely the benefits from conventional miniaturized chromatography

  18. Low-power, miniature {sup 171}Yb ion clock using an ultra-small vacuum package

    Energy Technology Data Exchange (ETDEWEB)

    Jau, Y.-Y.; Schwindt, P. D. D. [Sandia National Laboratories, Albuquerque, New Mexico 87185 (United States); Partner, H. [Sandia National Laboratories, Albuquerque, New Mexico 87185 (United States); Center for Quantum Information and Control (CQuIC), Department of Physics and Astronomy, University of New Mexico, Albuquerque, New Mexico 87131 (United States); Prestage, J. D.; Kellogg, J. R.; Yu, N. [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, California 91109 (United States)

    2012-12-17

    We report a demonstration of a very small microwave atomic clock using the 12.6 GHz hyperfine transition of the trapped {sup 171}Yb ions inside a miniature, completely sealed-off 3 cm{sup 3} ion-trap vacuum package. In the ion clock system, all of the components are highly miniaturized with low power consumption except the 369 nm optical pumping laser still under development for miniaturization. The entire clock, including the control electronics, consumes <300 mW. The fractional frequency instability of the miniature Yb{sup +} clock reaches the 10{sup -14} range after a few days of integration.

  19. High Performance Miniature Bandpass Filters, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This proposal is submitted for developing low impedance, miniature bandpass RF frequency filter via MEMS technique, in applications of SMAP, Aquarius follow-on,...

  20. A Spectral Reconstruction Algorithm of Miniature Spectrometer Based on Sparse Optimization and Dictionary Learning.

    Science.gov (United States)

    Zhang, Shang; Dong, Yuhan; Fu, Hongyan; Huang, Shao-Lun; Zhang, Lin

    2018-02-22

    The miniaturization of spectrometer can broaden the application area of spectrometry, which has huge academic and industrial value. Among various miniaturization approaches, filter-based miniaturization is a promising implementation by utilizing broadband filters with distinct transmission functions. Mathematically, filter-based spectral reconstruction can be modeled as solving a system of linear equations. In this paper, we propose an algorithm of spectral reconstruction based on sparse optimization and dictionary learning. To verify the feasibility of the reconstruction algorithm, we design and implement a simple prototype of a filter-based miniature spectrometer. The experimental results demonstrate that sparse optimization is well applicable to spectral reconstruction whether the spectra are directly sparse or not. As for the non-directly sparse spectra, their sparsity can be enhanced by dictionary learning. In conclusion, the proposed approach has a bright application prospect in fabricating a practical miniature spectrometer.

  1. Tensile and Creep Testing of Sanicro 25 Using Miniature Specimens

    Science.gov (United States)

    Dymáček, Petr; Jarý, Milan; Dobeš, Ferdinand; Kloc, Luboš

    2018-01-01

    Tensile and creep properties of new austenitic steel Sanicro 25 at room temperature and operating temperature 700 °C were investigated by testing on miniature specimens. The results were correlated with testing on conventional specimens. Very good agreement of results was obtained, namely in yield and ultimate strength, as well as short-term creep properties. Although the creep rupture time was found to be systematically shorter and creep ductility lower in the miniature test, the minimum creep rates were comparable. The analysis of the fracture surfaces revealed similar ductile fracture morphology for both specimen geometries. One exception was found in a small area near the miniature specimen edge that was cut by electro discharge machining, where an influence of the steel fracture behavior at elevated temperature was identified. PMID:29337867

  2. Tensile and Creep Testing of Sanicro 25 Using Miniature Specimens.

    Science.gov (United States)

    Dymáček, Petr; Jarý, Milan; Dobeš, Ferdinand; Kloc, Luboš

    2018-01-16

    Tensile and creep properties of new austenitic steel Sanicro 25 at room temperature and operating temperature 700 °C were investigated by testing on miniature specimens. The results were correlated with testing on conventional specimens. Very good agreement of results was obtained, namely in yield and ultimate strength, as well as short-term creep properties. Although the creep rupture time was found to be systematically shorter and creep ductility lower in the miniature test, the minimum creep rates were comparable. The analysis of the fracture surfaces revealed similar ductile fracture morphology for both specimen geometries. One exception was found in a small area near the miniature specimen edge that was cut by electro discharge machining, where an influence of the steel fracture behavior at elevated temperature was identified.

  3. Miniature specimen technology for postirradiation fatigue crack growth testing

    International Nuclear Information System (INIS)

    Mervyn, D.A.; Ermi, A.M.

    1979-01-01

    Current magnetic fusion reactor design concepts require that the fatigue behavior of candidate first wall materials be characterized. Fatigue crack growth may, in fact, be the design limiting factor in these cyclic reactor concepts given the inevitable presence of crack-like flaws in fabricated sheet structures. Miniature specimen technology has been developed to provide the large data base necessary to characterize irradiation effects on the fatigue crack growth behavior. An electrical potential method of measuring crack growth rates is employed on miniature center-cracked-tension specimens (1.27 cm x 2.54 cm x 0.061 cm). Results of a baseline study on 20% cold-worked 316 stainless steel, which was tested in an in-cell prototypic fatigue machine, are presented. The miniature fatigue machine is designed for low cost, on-line, real time testing of irradiated fusion candidate alloys. It will enable large scale characterization and development of candidate first wall alloys

  4. Narrative Metamorphosis Through Images: The Case of Opening Miniatures in the Estoire del

    Directory of Open Access Journals (Sweden)

    Miha Zor

    2015-12-01

    Full Text Available The article deals with pictorial metamorphosis in the opening pages of two early 14th-century manuscripts of the Estoire del saint Graal. Firstly, the episodes depicted are analysed iconographically and formally. Secondly, it explores how pictorial narrative is established in the multi-compartmentalised miniature, that is how the images are linked internally in order to convey a narrative that has its beginning and its ending. Thirdly, it is shown how the images in the opening miniature communicate with other miniatures in the manuscript and how the course of interpretation, signaled by the opening miniature, is succeeded and confirmed by the selection of episodes which are subsequently depicted, as well as by the way in which the episodes depicted are pictorially interpreted.

  5. Generation of an isogenic, gene-corrected iPSC line from a pre-symptomatic 28-year-old woman with an R406W mutation in the microtubule associated protein tau (MAPT) gene

    DEFF Research Database (Denmark)

    Nimsanor, Natakarn; Poulsen, Ulla; Rasmussen, Mikkel A.

    2016-01-01

    pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required cell type. Furthermore, gene-editing approaches allow generating isogenic gene-corrected controls that can be used as a very specific control. Here, we report the generation......Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the MAPT (microtubule-associated protein tau) gene can cause FTDP-17, but the underlying pathomechanisms of the disease are still unknown. Induced...... of genetically corrected iPSCs from a pre-symptomatic carrier of the R406W mutation in the MAPT-gene....

  6. Miniature and micro mass spectrometry for nanoscale sensing applications

    International Nuclear Information System (INIS)

    Taylor, S; France, N

    2009-01-01

    In recent years the use of miniature and/or microscale versions of the more popular mass spectrometers have been realised. This has led to the development of portable analytical devices for a range of 'in the field' sensing applications in aerospace, environmental monitoring, medical diagnosis and process control. In this paper the principles underpinning the development of miniature quadrupole mass spectrometers are reviewed. Two different microfabrication methods are compared with a conventional QMS used for residual gas analysis in the range 1-100 Da.

  7. EMC, RF, and Antenna Systems in Miniature Electronic Devices

    DEFF Research Database (Denmark)

    Ruaro, Andrea

    Advanced techniques for the control of electromagnetic interference (EMI) and for the optimization of the electromagnetic compatibility (EMC) performance has been developed under the constraints typical of miniature electronic devices (MED). The electromagnetic coexistence of multiple systems....... The structure allows for effective suppression of radiation from the MED, while taking into consideration the integration and miniaturization aspects. To increase the sensitivity of the system, a compact LNA suitable for on-body applications has been developed. The LNA allows for an increase in the overall...

  8. A Spectral Reconstruction Algorithm of Miniature Spectrometer Based on Sparse Optimization and Dictionary Learning

    Science.gov (United States)

    Zhang, Shang; Fu, Hongyan; Huang, Shao-Lun; Zhang, Lin

    2018-01-01

    The miniaturization of spectrometer can broaden the application area of spectrometry, which has huge academic and industrial value. Among various miniaturization approaches, filter-based miniaturization is a promising implementation by utilizing broadband filters with distinct transmission functions. Mathematically, filter-based spectral reconstruction can be modeled as solving a system of linear equations. In this paper, we propose an algorithm of spectral reconstruction based on sparse optimization and dictionary learning. To verify the feasibility of the reconstruction algorithm, we design and implement a simple prototype of a filter-based miniature spectrometer. The experimental results demonstrate that sparse optimization is well applicable to spectral reconstruction whether the spectra are directly sparse or not. As for the non-directly sparse spectra, their sparsity can be enhanced by dictionary learning. In conclusion, the proposed approach has a bright application prospect in fabricating a practical miniature spectrometer. PMID:29470406

  9. Generation of human iPSC line GRX-MCiPS4F-A2 from adult peripheral blood mononuclear cells (PBMCs with Spanish genetic background

    Directory of Open Access Journals (Sweden)

    Sonia Cabrera

    2015-09-01

    Full Text Available We have generated iPSCs from peripheral blood mononuclear cells (PBMCs of a healthy man using heat sensitive and non-integrative Sendai virus containing Sox2, Oct3/4, c-Myc and Klf4. Human GRX-MCiPS4F-A2 cell line was established and characterized through this study.

  10. Pain-related increase of excitatory transmission and decrease of inhibitory transmission in the central nucleus of the amygdala are mediated by mGluR1

    Directory of Open Access Journals (Sweden)

    Neugebauer Volker

    2010-12-01

    mechanism. An mGluR5 antagonist (MTEP inhibited both excitatory and inhibitory transmission in slices from normal and from arthritic rats. The analysis of spontaneous and miniature EPSCs and IPSCs showed that mGluR1 acted presynaptically whereas mGluR5 had postsynaptic effects. In conclusion, mGluR1 rather than mGluR5 can account for the pain-related changes of excitatory and inhibitory synaptic transmission in the CeLC through a mechanism that involves inhibition of inhibitory transmission (disinhibition.

  11. Plasma Structure and Behavior of Miniature Ring-Cusp Discharges

    Science.gov (United States)

    Mao, Hann-Shin

    Miniature ring-cusp ion thrusters provide a unique blend of high efficiencies and millinewton level thrust for future spacecraft. These thrusters are attractive as a primary propulsion for small satellites that require a high delta V, and as a secondary propulsion for larger spacecraft that require precision formation flying, disturbance rejection, or attitude control. To ensure desirable performance throughout the life of such missions, an advancement in the understanding of the plasma structure and behavior of miniature ring-cusp discharges is required. A research model was fabricated to provide a simplified experimental test bed for the analysis of the plasma discharge chamber of a miniature ion thruster. The plasma source allowed for spatially resolved measurements with a Langmuir probe along a meridian plane. Probe measurements yielded plasma density, electron temperature, and plasma potential data. The magnetic field strength was varied along with the discharge current to determine the plasma behavior under various conditions. The structure of the plasma properties were found to be independent of the discharge power under the proper scaling. It was concluded that weaker magnetic fields can improve the overall performance for ion thruster operation. To further analyze the experimental measurements, a framework was developed based on the magnetic field. A flux aligned coordinate system was developed to decouple the perpendicular and parallel plasma motion with respect to the magnetic field. This was done using the stream function and magnetic scalar potential. Magnetic formulae provided intuition on the field profiles dependence on magnet dimensions. The flux aligned coordinate system showed that the plasma was isopycnic along constant stream function values. This was used to develop an empirical relation suitable for estimating the spatial behavior and to determine the plasma volume and loss areas. The plasma geometry estimates were applied to a control volume

  12. A miniature X-ray tube based on carbon nanotube for an intraoral dental radiography

    International Nuclear Information System (INIS)

    Kim, Hyun Jin; Park, Han Beom; Lee, Ju Hyuk; Cho, Sung Oh

    2016-01-01

    The number of human teeth that can be radiographically taken is limited. Moreover, at least two X-ray shots are required to get images of teeth from both sides of the mouth. In order to overcome the disadvantages of conventional dental radiography, a dental radiograph has been proposed in which an X-ray tube is inserted into the mouth while an X-ray detector is placed outside the mouth. The miniature X-ray tube is required small size to insert into the mouth. Recently, we have fabricated a miniature x-ray tube with the diameter of 7 mm using a carbon nanotube (CNT) field. But, commercialized miniature X-ray tube were adopted a thermionic type using tungsten filament. The X-ray tubes adopted thermionic emission has a disadvantage of increasing temperature of x-ray tube. So it need to cooling system to cool x-ray tube. On the other hands, X-ray tubes adopted CNT field emitters don't need cooling systems because electrons are emitted from CNT by applying high voltage without heating. We have developed the miniature x-ray tube that produce x-ray with uniform spatial distribution based on carbon nanotube field emitters. The fabricated miniature x-ray tube can be stably and reliably operated at 50kV without any vacuum pump. The developed miniature X-ray tube was applied for intraoral dental radiography that employs an intra-oral CNT-based miniature X-ray tube and extra-oral X-ray detectors. An X-ray image of many teeth was successfully obtained by a single X-ray shot using the intra-oral miniature X-ray tube system. Furthermore, images of both molar teeth of pig were simultaneously obtained by a single X-ray shot. These results show that the intraoral dental radiography, which employs an intraoral miniature X-ray tube and an extraoral X-ray detector, performs better than conventional dental radiography

  13. A miniature X-ray tube based on carbon nanotube for an intraoral dental radiography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Jin; Park, Han Beom; Lee, Ju Hyuk; Cho, Sung Oh [KAIST, Daejeon (Korea, Republic of)

    2016-05-15

    The number of human teeth that can be radiographically taken is limited. Moreover, at least two X-ray shots are required to get images of teeth from both sides of the mouth. In order to overcome the disadvantages of conventional dental radiography, a dental radiograph has been proposed in which an X-ray tube is inserted into the mouth while an X-ray detector is placed outside the mouth. The miniature X-ray tube is required small size to insert into the mouth. Recently, we have fabricated a miniature x-ray tube with the diameter of 7 mm using a carbon nanotube (CNT) field. But, commercialized miniature X-ray tube were adopted a thermionic type using tungsten filament. The X-ray tubes adopted thermionic emission has a disadvantage of increasing temperature of x-ray tube. So it need to cooling system to cool x-ray tube. On the other hands, X-ray tubes adopted CNT field emitters don't need cooling systems because electrons are emitted from CNT by applying high voltage without heating. We have developed the miniature x-ray tube that produce x-ray with uniform spatial distribution based on carbon nanotube field emitters. The fabricated miniature x-ray tube can be stably and reliably operated at 50kV without any vacuum pump. The developed miniature X-ray tube was applied for intraoral dental radiography that employs an intra-oral CNT-based miniature X-ray tube and extra-oral X-ray detectors. An X-ray image of many teeth was successfully obtained by a single X-ray shot using the intra-oral miniature X-ray tube system. Furthermore, images of both molar teeth of pig were simultaneously obtained by a single X-ray shot. These results show that the intraoral dental radiography, which employs an intraoral miniature X-ray tube and an extraoral X-ray detector, performs better than conventional dental radiography.

  14. Miniaturized Aptamer-Based Assays for Protein Detection

    Directory of Open Access Journals (Sweden)

    Alessandro Bosco

    2016-09-01

    Full Text Available The availability of devices for cancer biomarker detection at early stages of the disease is one of the most critical issues in biomedicine. Towards this goal, to increase the assay sensitivity, device miniaturization strategies empowered by the employment of high affinity protein binders constitute a valuable approach. In this work we propose two different surface-based miniaturized platforms for biomarker detection in body fluids: the first platform is an atomic force microscopy (AFM-based nanoarray, where AFM is used to generate functional nanoscale areas and to detect biorecognition through careful topographic measurements; the second platform consists of a miniaturized electrochemical cell to detect biomarkers through electrochemical impedance spectroscopy (EIS analysis. Both devices rely on robust and highly-specific protein binders as aptamers, and were tested for thrombin detection. An active layer of DNA-aptamer conjugates was immobilized via DNA directed immobilization on complementary single-stranded DNA self-assembled monolayers confined on a nano/micro area of a gold surface. Results obtained with these devices were compared with the output of surface plasmon resonance (SPR assays used as reference. We succeeded in capturing antigens in concentrations as low as a few nM. We put forward ideas to push the sensitivity further to the pM range, assuring low biosample volume (μL range assay conditions.

  15. Does Spontaneous Favorability to Power (vs. Universalism) Values Predict Spontaneous Prejudice and Discrimination?

    Science.gov (United States)

    Souchon, Nicolas; Maio, Gregory R; Hanel, Paul H P; Bardin, Brigitte

    2017-10-01

    We conducted five studies testing whether an implicit measure of favorability toward power over universalism values predicts spontaneous prejudice and discrimination. Studies 1 (N = 192) and 2 (N = 86) examined correlations between spontaneous favorability toward power (vs. universalism) values, achievement (vs. benevolence) values, and a spontaneous measure of prejudice toward ethnic minorities. Study 3 (N = 159) tested whether conditioning participants to associate power values with positive adjectives and universalism values with negative adjectives (or inversely) affects spontaneous prejudice. Study 4 (N = 95) tested whether decision bias toward female handball players could be predicted by spontaneous attitude toward power (vs. universalism) values. Study 5 (N = 123) examined correlations between spontaneous attitude toward power (vs. universalism) values, spontaneous importance toward power (vs. universalism) values, and spontaneous prejudice toward Black African people. Spontaneous positivity toward power (vs. universalism) values was associated with spontaneous negativity toward minorities and predicted gender bias in a decision task, whereas the explicit measures did not. These results indicate that the implicit assessment of evaluative responses attached to human values helps to model value-attitude-behavior relations. © 2016 The Authors. Journal of Personality Published by Wiley Periodicals, Inc.

  16. Microsupercapacitors as miniaturized energy-storage components for on-chip electronics

    Science.gov (United States)

    Kyeremateng, Nana Amponsah; Brousse, Thierry; Pech, David

    2017-01-01

    The push towards miniaturized electronics calls for the development of miniaturized energy-storage components that can enable sustained, autonomous operation of electronic devices for applications such as wearable gadgets and wireless sensor networks. Microsupercapacitors have been targeted as a viable route for this purpose, because, though storing less energy than microbatteries, they can be charged and discharged much more rapidly and have an almost unlimited lifetime. In this Review, we discuss the progress and the prospects of integrated miniaturized supercapacitors. In particular, we discuss their power performances and emphasize the need of a three-dimensional design to boost their energy-storage capacity. This is obtainable, for example, through self-supported nanostructured electrodes. We also critically evaluate the performance metrics currently used in the literature to characterize microsupercapacitors and offer general guidelines to benchmark performances towards prospective applications.

  17. Miniature Active Space Radiation Dosimeter, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Space Micro will extend our Phase I R&D to develop a family of miniature, active space radiation dosimeters/particle counters, with a focus on biological/manned...

  18. Induced pluripotent stem cells (iPSCs) derived from a patient with frontotemporal dementia caused by a R406W mutation in microtubule-associated protein tau (MAPT)

    DEFF Research Database (Denmark)

    Rasmussen, Mikkel A.; Hjermind, Lena E.; Hasholt, Lis F.

    2016-01-01

    Skin fibroblasts were obtained from a 59-year-old woman diagnosed with frontotemporal dementia. The disease is caused by a R406W mutation in microtubule-associated protein tau (MAPT). Induced pluripotent stem cells (iPSCs) were established by electroporation with episomal plasmids containing hOCT4...

  19. Miniaturized radiation chirper

    International Nuclear Information System (INIS)

    Umbarger, C.J.; Wolf, M.A.

    1980-01-01

    A miniaturized radiation chirper for use with a small battery supplying on the order of 5 volts is described. A poor quality CdTe crystal which is not necessarily suitable for high resolution gamma ray spectroscopy is incorporated with appropriate electronics so that the chirper emits an audible noise at a rate that is proportional to radiation exposure level. The chirper is intended to serve as a personnel radiation warning device that utilizes new and novel electronics with a novel detector, a CdTe crystal. The resultant device is much smaller and has much longer battery life than existing chirpers

  20. Miniaturized integration of a fluorescence microscope

    Science.gov (United States)

    Ghosh, Kunal K.; Burns, Laurie D.; Cocker, Eric D.; Nimmerjahn, Axel; Ziv, Yaniv; Gamal, Abbas El; Schnitzer, Mark J.

    2013-01-01

    The light microscope is traditionally an instrument of substantial size and expense. Its miniaturized integration would enable many new applications based on mass-producible, tiny microscopes. Key prospective usages include brain imaging in behaving animals towards relating cellular dynamics to animal behavior. Here we introduce a miniature (1.9 g) integrated fluorescence microscope made from mass-producible parts, including semiconductor light source and sensor. This device enables high-speed cellular-level imaging across ∼0.5 mm2 areas in active mice. This capability allowed concurrent tracking of Ca2+ spiking in >200 Purkinje neurons across nine cerebellar microzones. During mouse locomotion, individual microzones exhibited large-scale, synchronized Ca2+ spiking. This is a mesoscopic neural dynamic missed by prior techniques for studying the brain at other length scales. Overall, the integrated microscope is a potentially transformative technology that permits distribution to many animals and enables diverse usages, such as portable diagnostics or microscope arrays for large-scale screens. PMID:21909102

  1. EZ spheres: a stable and expandable culture system for the generation of pre-rosette multipotent stem cells from human ESCs and iPSCs.

    Science.gov (United States)

    Ebert, Allison D; Shelley, Brandon C; Hurley, Amanda M; Onorati, Marco; Castiglioni, Valentina; Patitucci, Teresa N; Svendsen, Soshana P; Mattis, Virginia B; McGivern, Jered V; Schwab, Andrew J; Sareen, Dhruv; Kim, Ho Won; Cattaneo, Elena; Svendsen, Clive N

    2013-05-01

    We have developed a simple method to generate and expand multipotent, self-renewing pre-rosette neural stem cells from both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs) without utilizing embryoid body formation, manual selection techniques, or complex combinations of small molecules. Human ESC and iPSC colonies were lifted and placed in a neural stem cell medium containing high concentrations of EGF and FGF-2. Cell aggregates (termed EZ spheres) could be expanded for long periods using a chopping method that maintained cell-cell contact. Early passage EZ spheres rapidly down-regulated OCT4 and up-regulated SOX2 and nestin expression. They retained the potential to form neural rosettes and consistently differentiated into a range of central and peripheral neural lineages. Thus, they represent a very early neural stem cell with greater differentiation flexibility than other previously described methods. As such, they will be useful for the rapidly expanding field of neurological development and disease modeling, high-content screening, and regenerative therapies based on pluripotent stem cell technology. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Generation of induced pluripotent stem cells (iPSC) from an atrial fibrillation patient carrying a KCNA5 p.D322H mutation

    DEFF Research Database (Denmark)

    Mora, Cristina; Serzanti, Marialaura; Giacomelli, Alessio

    2017-01-01

    . To investigate the molecular mechanisms underlying AF, we reprogrammed to pluripotency polymorphonucleated leukocytes isolated from the blood of a patient carrying a KCNA5 p.D322H mutation, using a commercially available non-integrating system. The generated iPSCs expressed pluripotency markers...... and differentiated toward cells belonging to the three embryonic germ layers. Moreover, the cells showed a normal karyotype and retained the p.D322H mutation....

  3. Generation of induced pluripotent stem cells (iPSC) from an atrial fibrillation patient carrying a PITX2 p.M200V mutation

    DEFF Research Database (Denmark)

    Mora, Cristina; Serzanti, Marialaura; Giacomelli, Alessio

    2017-01-01

    the molecular mechanisms underlying AF, we reprogrammed to pluripotency polymorphonucleated leukocytes isolated from the blood of a patient carrying a PITX2 p.M200V mutation, using a commercially available non-integrating expression system. The generated iPSCs expressed pluripotency markers and differentiated...... toward cells belonging to the three embryonic germ layers. Moreover, the cells showed a normal karyotype and retained the PITX2 p.M200V mutation....

  4. Miniature magnetic fluid seal working in liquid environments

    Energy Technology Data Exchange (ETDEWEB)

    Mitamura, Yoshinori, E-mail: ymitamura@par.odn.ne.jp [Graduate School of Information Science and Technology, Hokkaido University, Sapporo 060-0814 (Japan); Durst, Christopher A., E-mail: chris@procyrion.com [Procyrion, Inc., Houston, TX 77027 (United States)

    2017-06-01

    This study was carried out to develop a miniature magnetic fluid (MF) seal working in a liquid environment. The miniature MF seal is intended for use in a catheter blood pump. The requirements for the MF seal included a size of less than Ø4×4.5 mm, shaft diameter of 1 mm, sealing pressure of 200 mmHg, shaft speed of up to 40000 rpm, and life of one month. The miniature MF seal was composed of an NdFeB magnet (Ø4×Ø2×1) sandwiched between two pole pieces (Ø4×Ø1.1×0.5). A shield (Ø4×Ø1.2×1.5) was placed on the pole piece facing the liquid to minimize the influence of pump flow on the MF. The seal was installed on a Ø1 shaft. A seal was formed by injecting MF (Ms: 47.8 kA/m and η: 0.5 Pa·sec) into the gap between the pole pieces and the shaft. Total volume of the MF seal was 44 μL. A sealing pressure of 370 mmHg was obtained at motor speeds of 0-40,000 rpm. The seal remained perfect for 10 days in saline under the condition of a pump flow of 1.5 L/min (The test was terminated in accordance with plans). The seal remained intact after ethylene oxide sterilization during which the seal was exposed to high pressures. In conclusion, the newly developed MF seal will be useful for a catheter pump. - Highlights: • A miniature magnetic fluid seal working in a liquid environment was developed. • The seal can be installed on Ø1 mm shaft and can seal against 370 mmHg at 40000 rpm. • The magnetic fluid seal will be useful for a catheter blood pump.

  5. Modelling Fanconi anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs.

    Science.gov (United States)

    Liu, Guang-Hui; Suzuki, Keiichiro; Li, Mo; Qu, Jing; Montserrat, Nuria; Tarantino, Carolina; Gu, Ying; Yi, Fei; Xu, Xiuling; Zhang, Weiqi; Ruiz, Sergio; Plongthongkum, Nongluk; Zhang, Kun; Masuda, Shigeo; Nivet, Emmanuel; Tsunekawa, Yuji; Soligalla, Rupa Devi; Goebl, April; Aizawa, Emi; Kim, Na Young; Kim, Jessica; Dubova, Ilir; Li, Ying; Ren, Ruotong; Benner, Chris; Del Sol, Antonio; Bueren, Juan; Trujillo, Juan Pablo; Surralles, Jordi; Cappelli, Enrico; Dufour, Carlo; Esteban, Concepcion Rodriguez; Belmonte, Juan Carlos Izpisua

    2014-07-07

    Fanconi anaemia (FA) is a recessive disorder characterized by genomic instability, congenital abnormalities, cancer predisposition and bone marrow (BM) failure. However, the pathogenesis of FA is not fully understood partly due to the limitations of current disease models. Here, we derive integration free-induced pluripotent stem cells (iPSCs) from an FA patient without genetic complementation and report in situ gene correction in FA-iPSCs as well as the generation of isogenic FANCA-deficient human embryonic stem cell (ESC) lines. FA cellular phenotypes are recapitulated in iPSCs/ESCs and their adult stem/progenitor cell derivatives. By using isogenic pathogenic mutation-free controls as well as cellular and genomic tools, our model serves to facilitate the discovery of novel disease features. We validate our model as a drug-screening platform by identifying several compounds that improve hematopoietic differentiation of FA-iPSCs. These compounds are also able to rescue the hematopoietic phenotype of FA patient BM cells.

  6. Modeling Fanconi Anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs

    Science.gov (United States)

    Montserrat, Nuria; Tarantino, Carolina; Gu, Ying; Yi, Fei; Xu, Xiuling; Zhang, Weiqi; Ruiz, Sergio; Plongthongkum, Nongluk; Zhang, Kun; Masuda, Shigeo; Nivet, Emmanuel; Tsunekawa, Yuji; Soligalla, Rupa Devi; Goebl, April; Aizawa, Emi; Kim, Na Young; Kim, Jessica; Dubova, Ilir; Li, Ying; Ren, Ruotong; Benner, Chris; del Sol, Antonio; Bueren, Juan; Trujillo, Juan Pablo; Surralles, Jordi; Cappelli, Enrico; Dufour, Carlo; Esteban, Concepcion Rodriguez; Belmonte, Juan Carlos Izpisua

    2014-01-01

    Fanconi Anemia (FA) is a recessive disorder characterized by genomic instability, congenital abnormalities, cancer predisposition and bone marrow failure. However, the pathogenesis of FA is not fully understood partly due to the limitations of current disease models. Here, we derive integration-free induced pluripotent stem cells (iPSCs) from an FA patient without genetic complementation and report in situ gene correction in FA-iPSCs as well as the generation of isogenic FANCA deficient human embryonic stem cell (ESC) lines. FA cellular phenotypes are recapitulated in iPSCs/ESCs and their adult stem/progenitor cell derivatives. By using isogenic pathogenic mutation-free controls as well as cellular and genomic tools, our model serves to facilitate the discovery of novel disease features. We validate our model as a drug-screening platform by identifying several compounds that improve hematopoietic differentiation of FA-iPSCs. These compounds are also able to rescue the hematopoietic phenotype of FA-patient bone marrow cells. PMID:24999918

  7. Modeling high-temperature superconductors and metallic alloys on the Intel IPSC/860

    Science.gov (United States)

    Geist, G. A.; Peyton, B. W.; Shelton, W. A.; Stocks, G. M.

    Oak Ridge National Laboratory has embarked on several computational Grand Challenges, which require the close cooperation of physicists, mathematicians, and computer scientists. One of these projects is the determination of the material properties of alloys from first principles and, in particular, the electronic structure of high-temperature superconductors. While the present focus of the project is on superconductivity, the approach is general enough to permit study of other properties of metallic alloys such as strength and magnetic properties. This paper describes the progress to date on this project. We include a description of a self-consistent KKR-CPA method, parallelization of the model, and the incorporation of a dynamic load balancing scheme into the algorithm. We also describe the development and performance of a consolidated KKR-CPA code capable of running on CRAYs, workstations, and several parallel computers without source code modification. Performance of this code on the Intel iPSC/860 is also compared to a CRAY 2, CRAY YMP, and several workstations. Finally, some density of state calculations of two perovskite superconductors are given.

  8. Evolution in miniaturized column liquid chromatography instrumentation and applications: An overview.

    Science.gov (United States)

    Nazario, Carlos E D; Silva, Meire R; Franco, Maraíssa S; Lanças, Fernando M

    2015-11-20

    The purpose of this article is to underline the miniaturized LC instrumental system and describe the evolution of commercially available systems by discussing their advantages and drawbacks. Nowadays, there are already many miniaturized LC systems available with a great variety of pump design, interface and detectors as well as efficient columns technologies and reduced connections devices. The solvent delivery systems are able to drive the mobile phase without flow splitters and promote gradient elution using either dual piston reciprocating or syringe-type pumps. The mass spectrometry as detection system is the most widely used detection system; among many alternative ionization sources direct-EI LC-MS is a promising alternative to APCI. In addition, capillary columns are now available showing many possibilities of stationary phases, inner diameters and hardware materials. This review provides a discussion about miniaturized LC demonstrating fundamentals and instrumentals' aspects of the commercially available miniaturized LC instrumental system mainly nano and micro LC formats. This review also covers the recent developments and trends in instrumentation, capillary and nano columns, and several applications of this very important and promising field. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. An Intraoral Miniature X-ray Tube Based on Carbon Nanotubes for Dental Radiography

    OpenAIRE

    Hyun Jin Kim; Hyun Nam Kim; Hamid Saeed Raza; Han Beom Park; Sung Oh Cho

    2016-01-01

    A miniature X-ray tube based on a carbon-nanotube electron emitter has been employed for the application to a dental radiography. The miniature X-ray tube has an outer diameter of 7 mm and a length of 47 mm. The miniature X-ray tube is operated in a negative high-voltage mode in which the X-ray target is electrically grounded. In addition, X-rays are generated only to the teeth directions using a collimator while X-rays generated to other directions are shielded. Hence, the X-ray tube can be ...

  10. Miniature fiber Bragg grating sensor interrogator (FBG-Transceiver) system

    Science.gov (United States)

    Mendoza, Edgar A.; Kempen, Cornelia; Lopatin, Craig

    2007-04-01

    This paper describes recent progress conducted towards the development of a miniature fiber Bragg grating sensor interrogator (FBG-Transceiver TM) system based on multi-channel integrated optic sensor (InOSense TM) microchip technology. The hybrid InOSense TM microchip technology enables the integration of all of the functionalities, both passive and active, of conventional bench top FBG sensor interrogator systems, packaged in a miniaturized, low power operation, 2-cm x 5-cm package suitable for the long-term structural health monitoring in applications where size, weight, and power are critical for operation. The FBG-Transceiver system uses active optoelectronic components monolithically integrated to the InOSense TM microchip, a microprocessor controlled signal processing electronics board capable of processing the FBG sensors signals related to stress-strain and temperature as well as vibration and acoustics. The FBG-Transceiver TM system represents a new, reliable, highly robust technology that can be used to accurately monitor the status of an array of distributed fiber optic Bragg grating sensors installed in critical infrastructures. Its miniature package, low power operation, and state-of-the-art data communications architecture, all at a very affordable price makes it a very attractive solution for a large number of SHM/NDI applications in aerospace, naval and maritime industry, civil structures like bridges, buildings and dams, the oil and chemical industry, and for homeland security applications. The miniature, cost-efficient FBG-Transceiver TM system is poised to revolutionize the field of structural health monitoring and nondestructive inspection market. The sponsor of this program is NAVAIR under a DOD SBIR contract.

  11. MIT miniaturized disk bend test

    International Nuclear Information System (INIS)

    Harling, O.K.; Lee, M.; Sohn, D.S.; Kohse, G.; Lau, C.W.

    1983-01-01

    A miniaturized disk bend test (MDBT) using transmission electron microscopy specimens for the determination of various mechanical properties is being developed at MIT. Recent progress in obtaining strengths and ductilities of highly irradiated metal alloys is reviewed. Other mechanical properties can also be obtained using the MDBT approach. Progress in fatigue testing and in determination of the ductile-to-brittle transition temperature is reviewed briefly. 11 figures

  12. High prevalence of the c.74A>C SPINK1 variant in miniature and standard Schnauzers.

    Science.gov (United States)

    Furrow, E; Armstrong, P J; Patterson, E E

    2012-01-01

    Variants in the serine protease inhibitor Kazal type 1 (SPINK1) gene have been associated with pancreatitis in Miniature Schnauzers. Replication of the association in an independent population is necessary to determine if genetic screening for SPINK1 variants should be considered in clinical practice. An association between the SPINK1 exonic variant c.74A > C and pancreatitis exists in Miniature Schnauzers. In addition, the variant is absent or rare in Standard Schnauzers, a related breed that is not reported to have an increased risk for pancreatitis. Case-control study. Seventeen Miniature Schnauzers with pancreatitis (cases), 60 mature Miniature Schnauzers with no substantial history of gastrointestinal signs in their lifetime (controls), and 31 Standard Schnauzers of unknown pancreatitis status. A PCR-RFLP assay was used to genotype dogs for the c.74A > C SPINK1 variant. Allele and genotype frequencies were reported for Schnauzers and compared between case and control Miniature Schnauzers. The c.74A > C variant was the major allele in both Schnauzer breeds with a frequency of 0.77 in Miniatures and 0.55 in Standards. The allele and genotype frequencies were similar between Miniature Schnauzers with and without a history of pancreatitis and did not impart an increased risk for pancreatitis. Genotyping a larger population of the Miniature Schnauzer breed than a previous study, along with a Standard Schnauzer cohort, demonstrated that the SPINK1 c.74A > C variant is a common polymorphism in the Schnauzer lineage. Furthermore, we were unable to confirm a relationship between the variant and clinically detectable pancreatitis in Miniature Schnauzers. Copyright © 2012 by the American College of Veterinary Internal Medicine.

  13. Miniature piezo electric vacuum inlet valve

    Science.gov (United States)

    Keville, Robert F.; Dietrich, Daniel D.

    1998-03-24

    A miniature piezo electric vacuum inlet valve having a fast pulse rate and is battery operated with variable flow capability. The low power (piezo electric valves which require preloading of the crystal drive mechanism and 120 Vac, thus the valve of the present invention is smaller by a factor of three.

  14. Induced pluripotent stem cells (iPSCs) derived from af pre-symptomatic carrier of a R406W mutation in microtubule-associated protein tau (MAPT) causing frontotemporal dementia

    DEFF Research Database (Denmark)

    Rasmussen, Mikkel A.; Hjermind, Lena Elisabeth; Hasholt, Lis Frydenreich

    2016-01-01

    Skin fibroblasts were obtained from a 28-year-old pre-symptomatic woman carrying a R406W mutation in microtubule-associated protein tau (MAPT), known to cause frontotemporal dementia. Induced pluripotent stem cell (iPSCs) were established by electroporation with episomal plasmids containing hOCT4...

  15. Miniature fiber-optic multiphoton microscopy system using frequency-doubled femtosecond Er-doped fiber laser.

    Science.gov (United States)

    Huang, Lin; Mills, Arthur K; Zhao, Yuan; Jones, David J; Tang, Shuo

    2016-05-01

    We report on a miniature fiber-optic multiphoton microscopy (MPM) system based on a frequency-doubled femtosecond Er-doped fiber laser. The femtosecond pulses from the laser source are delivered to the miniature fiber-optic probe at 1.58 µm wavelength, where a standard single mode fiber is used for delivery without the need of free-space dispersion compensation components. The beam is frequency-doubled inside the probe by a periodically poled MgO:LiNbO3 crystal. Frequency-doubled pulses at 786 nm with a maximum power of 80 mW and a pulsewidth of 150 fs are obtained and applied to excite intrinsic signals from tissues. A MEMS scanner, a miniature objective, and a multimode collection fiber are further used to make the probe compact. The miniature fiber-optic MPM system is highly portable and robust. Ex vivo multiphoton imaging of mammalian skins demonstrates the capability of the system in imaging biological tissues. The results show that the miniature fiber-optic MPM system using frequency-doubled femtosecond fiber laser can potentially bring the MPM imaging for clinical applications.

  16. Miniaturized star tracker for micro spacecraft with high angular rate

    Science.gov (United States)

    Li, Jianhua; Li, Zhifeng; Niu, Zhenhong; Liu, Jiaqi

    2017-10-01

    There is a clear need for miniaturized, lightweight, accurate and inexpensive star tracker for spacecraft with large anglar rate. To face these new constraints, the Beijing Institute of Space Long March Vehicle has designed, built and flown a low cost miniaturized star tracker that provides autonomous ("Lost in Space") inertial attitude determination, 2 Hz 3-axis star tracking, and digital imaging with embedded compression. Detector with high sensitivity is adopted to meet the dynamic and miniature requirement. A Sun and Moon avoiding method based on the calculation of Sun and Moon's vector by astronomical theory is proposed. The produced prototype weight 0.84kg, and can be used for a spacecraft with 6°/s anglar rate. The average angle measure error is less than 43 arc second. The ground verification and application of the star tracker during the pick-up flight test showed that the capability of the product meet the requirement.

  17. Massive and Reproducible Production of Liver Buds Entirely from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Takanori Takebe

    2017-12-01

    Full Text Available Summary: Organoid technology provides a revolutionary paradigm toward therapy but has yet to be applied in humans, mainly because of reproducibility and scalability challenges. Here, we overcome these limitations by evolving a scalable organ bud production platform entirely from human induced pluripotent stem cells (iPSC. By conducting massive “reverse” screen experiments, we identified three progenitor populations that can effectively generate liver buds in a highly reproducible manner: hepatic endoderm, endothelium, and septum mesenchyme. Furthermore, we achieved human scalability by developing an omni-well-array culture platform for mass producing homogeneous and miniaturized liver buds on a clinically relevant large scale (>108. Vascularized and functional liver tissues generated entirely from iPSCs significantly improved subsequent hepatic functionalization potentiated by stage-matched developmental progenitor interactions, enabling functional rescue against acute liver failure via transplantation. Overall, our study provides a stringent manufacturing platform for multicellular organoid supply, thus facilitating clinical and pharmaceutical applications especially for the treatment of liver diseases through multi-industrial collaborations. : With the goal of clinical translation of liver bud transplant therapy, Takebe et al. established a massive organoid production platform from endoderm, endothelial, and mesenchymal progenitor populations specified entirely from human iPSCs, reproducibly demonstrating functionality both in vitro and in vivo. Keywords: iPSC, liver bud, organoid, transplantation, self-organization, endothelial, mesenchymal, liver failure, clinical grade

  18. Plans for miniature machining at LASL

    International Nuclear Information System (INIS)

    Rhorer, R.L.

    1979-01-01

    A special shop for making miniature or very small parts is being established within the LASL Shop Department, and one of the machine tools for this shop is a high precision lathe. The report describes a method based on scale modeling analysis which was used to define the specific requirements for this lathe

  19. Fabrication of a Miniaturized ZnO Nanowire Accelerometer and Its Performance Tests

    Directory of Open Access Journals (Sweden)

    Hyun Chan Kim

    2016-09-01

    Full Text Available This paper reports a miniaturized piezoelectric accelerometer suitable for a small haptic actuator array. The accelerometer is made with zinc oxide (ZnO nanowire (NW grown on a copper wafer by a hydrothermal process. The size of the accelerometer is 1.5 × 1.5 mm2, thus fitting the 1.8 × 1.8 mm2 haptic actuator array cell. The detailed fabrication process of the miniaturized accelerometer is illustrated. Performance evaluation of the fabricated accelerometer is conducted by comparing it with a commercial piezoelectric accelerometer. The output current of the fabricated accelerometer increases linearly with the acceleration. The miniaturized ZnO NW accelerometer is feasible for acceleration measurement of small and lightweight devices.

  20. Miniaturized Airborne Imaging Central Server System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The innovation is a miniaturized airborne imaging central server system (MAICSS). MAICSS is designed as a high-performance-computer-based electronic backend that...

  1. Miniaturized Airborne Imaging Central Server System, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The innovation is a miniaturized airborne imaging central server system (MAICSS). MAICSS is designed as a high-performance computer-based electronic backend that...

  2. Miniaturized optical sensors based on lens arrays

    DEFF Research Database (Denmark)

    Hanson, Steen Grüner; Jakobsen, M.L.; Larsen, H.E.

    2005-01-01

    A suite of optical sensors based on the use of lenticular arrays for probing mechanical deflections will be displayed. The optical systems are well suited for miniaturization, and utilize speckles as the information-carriers. This implementation allows for acquiring directional information...

  3. Improved methods for reprogramming human dermal fibroblasts using fluorescence activated cell sorting.

    Directory of Open Access Journals (Sweden)

    David J Kahler

    Full Text Available Current methods to derive induced pluripotent stem cell (iPSC lines from human dermal fibroblasts by viral infection rely on expensive and lengthy protocols. One major factor contributing to the time required to derive lines is the ability of researchers to identify fully reprogrammed unique candidate clones from a mixed cell population containing transformed or partially reprogrammed cells and fibroblasts at an early time point post infection. Failure to select high quality colonies early in the derivation process results in cell lines that require increased maintenance and unreliable experimental outcomes. Here, we describe an improved method for the derivation of iPSC lines using fluorescence activated cell sorting (FACS to isolate single cells expressing the cell surface marker signature CD13(NEGSSEA4(POSTra-1-60(POS on day 7-10 after infection. This technique prospectively isolates fully reprogrammed iPSCs, and depletes both parental and "contaminating" partially reprogrammed fibroblasts, thereby substantially reducing the time and reagents required to generate iPSC lines without the use of defined small molecule cocktails. FACS derived iPSC lines express common markers of pluripotency, and possess spontaneous differentiation potential in vitro and in vivo. To demonstrate the suitability of FACS for high-throughput iPSC generation, we derived 228 individual iPSC lines using either integrating (retroviral or non- integrating (Sendai virus reprogramming vectors and performed extensive characterization on a subset of those lines. The iPSC lines used in this study were derived from 76 unique samples from a variety of tissue sources, including fresh or frozen fibroblasts generated from biopsies harvested from healthy or disease patients.

  4. Miniature Inertial and Augmentation Sensors for Integrated Inertial/GPS Based Navigation Applications

    Science.gov (United States)

    2010-03-01

    Magnetometer (Ref [23]) Until miniature atomic magnetometers transition from laboratory demonstration units to a mass produced product, fluxgate ...and/or magnetoresistive designs are a better suited magnetometer technology for a miniature navigation system. Figure 8 below shows the basic fluxgate ...is required to resolve magnetic field orientation. Fig 8. Fluxgate Magnetometer Schematic The PNI Sensor Corporation (Santa Rosa, CA

  5. Novel Miniature Spectrometer For Remote Chemical Detection

    International Nuclear Information System (INIS)

    Pipino, Andrew C.R.

    2000-01-01

    New chemical sensing technologies are critically important for addressing many of EM's priority needs as discussed in detail at http://emsp.em.doe.gov/needs. Many technology needs were addressed by this research. For example, improved detection strategies are needed for non-aqueous phase liquids (NAPL's), such as PCE (Cl2C=CCl2) and TCE (HClC=CCl2), which persist in the environment due their highly stable structures. By developing a miniature, ultra-sensitive, selective, and field-deployable detector for NAPL's, the approximate source location could be determined with minimal investigative expense. Contaminant plumes could also be characterized in detail. The miniature spectrometer developed under Project No.60231 could also permit accurate rate measurements in less time, either in the field or the laboratory, which are critically important in the development, testing, and ultimate utilization of models for describing contaminant transport. The technology could also be used for long-term groundwater monitoring or long-term stewardship in general. Many science needs are also addressed by the Project 60231, since the effort significantly advances the measurement science of chemical detection. Developed under Project No.60231, evanescent wave cavity ring-down spectroscopy (EW-CRDS) is a novel form of CRDS, which is an the emerging optical absorption technique. Several review articles on CRDS, which has been generally applied only to gas-phase diagnostics, have been published1-3. EW-CRDS4-10 forms the basis for a new class of chemical sensors that extends CRDS to other states of matter and leads to a miniaturized version of the concept. EW-CRDS uses miniature solid-state optical resonators that incorporate one or more total internal reflection (TIR) surfaces, which create evanescent waves. The evanescent waves emanate from the TIR surfaces, sampling the surrounding medium. The utility of evanescent waves in chemical analysis forms the basis for the field of attenuated

  6. Inherited retinal dysplasia and persistent hyperplastic primary vitreous in Miniature Schnauzer dogs.

    Science.gov (United States)

    Grahn, Bruce H; Storey, Eric S; McMillan, Catherine

    2004-01-01

    The objectives of this study were to define the clinical syndrome of retinal dysplasia and persistent primary vitreous in Miniature Schnauzer dogs and determine the etiology. We examined 106 Miniature Schnauzers using a biomicroscope and indirect ophthalmoscope. The anterior and posterior segments of affected dogs were photographed. Four enucleated eyes were examined using routine light microscopy and scanning electron microscopy. A pedigree was constructed and related dogs were test-bred to define the mode of inheritance of this syndrome. Congenital retinal dysplasia was confirmed in 24 of 106 related Miniature Schnauzer dogs. Physical and postmortem examinations revealed that congenital abnormalities were limited to the eyes. Biomicroscopic, indirect ophthalmoscopic, and neuro-ophthalmic examinations confirmed that some of these dogs were blind secondary to bilateral retinal dysplasia and detachment (nonattachment) (n = 13), and the remainder had generalized retinal dysplasia (n = 11). Fifteen of these dogs were also diagnosed with unilateral (n = 9) or bilateral (n = 6) persistent hyperplastic primary vitreous. Nutritional, infectious, or toxic etiologies were not evident on physical, postmortem, light microscopic, or transmitting and scanning electron microscopic examination of four affected Miniature Schnauzers. We examined the pedigree and determined that an autosomal recessive mode of inheritance was most likely. Three test-bred litters including those from affected parents, carrier and affected parents, and carrier parents confirmed this mode of inheritance. This study confirms that retinal dysplasia and persistent hyperplastic primary vitreous is a congenital abnormality that is inherited as an autosomal recessive condition in Miniature Schnauzers.

  7. Novel nootropic dipeptide Noopept increases inhibitory synaptic transmission in CA1 pyramidal cells.

    Science.gov (United States)

    Kondratenko, Rodion V; Derevyagin, Vladimir I; Skrebitsky, Vladimir G

    2010-05-31

    Effects of newly synthesized nootropic and anxiolytic dipeptide Noopept on inhibitory synaptic transmission in hippocampal CA1 pyramidal cells were investigated using patch-clamp technique in whole-cell configuration. Bath application of Noopept (1 microM) significantly increased the frequency of spike-dependant spontaneous IPSCs whereas spike-independent mIPSCs remained unchanged. It was suggested that Noopept mediates its effect due to the activation of inhibitory interneurons terminating on CA1 pyramidal cells. Results of current clamp recording of inhibitory interneurons residing in stratum radiatum confirmed this suggestion. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  8. An Intraoral Miniature X-ray Tube Based on Carbon Nanotubes for Dental Radiography

    Directory of Open Access Journals (Sweden)

    Hyun Jin Kim

    2016-06-01

    Full Text Available A miniature X-ray tube based on a carbon-nanotube electron emitter has been employed for the application to a dental radiography. The miniature X-ray tube has an outer diameter of 7 mm and a length of 47 mm. The miniature X-ray tube is operated in a negative high-voltage mode in which the X-ray target is electrically grounded. In addition, X-rays are generated only to the teeth directions using a collimator while X-rays generated to other directions are shielded. Hence, the X-ray tube can be safely inserted into a human mouth. Using the intra-oral X-ray tube, a dental radiography is demonstrated where the positions of an X-ray source and a sensor are reversed compared with a conventional dental radiography system. X-ray images of five neighboring teeth are obtained and, furthermore, both left and right molar images are achieved by a single X-ray shot of the miniature X-ray tube.

  9. An intraoral miniature x-ray tube based on carbon nanotubes for dental radiography

    International Nuclear Information System (INIS)

    Kim, Hyun Jin; Kim, Hyun Nam; Raza, Hamid Saeed; Park, Han Beom; Cho, Sung Oh

    2016-01-01

    A miniature X-ray tube based on a carbon-nanotube electron emitter has been employed for the application to a dental radiography. The miniature X-ray tube has an outer diameter of 7 mm and a length of 47 mm. The miniature X-ray tube is operated in a negative high-voltage mode in which the X-ray target is electrically grounded. In addition, X-rays are generated only to the teeth directions using a collimator while X-rays generated to other directions are shielded. Hence, the X-ray tube can be safely inserted into a human mouth. Using the intra-oral X-ray tube, a dental radiography is demonstrated where the positions of an X-ray source and a sensor are reversed compared with a conventional dental radiography system. X-ray images of five neighboring teeth are obtained and, furthermore, both left and right molar images are achieved by a single X-ray shot of the miniature X-ray tube

  10. An intraoral miniature x-ray tube based on carbon nanotubes for dental radiography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Jin; Kim, Hyun Nam; Raza, Hamid Saeed; Park, Han Beom; Cho, Sung Oh [Dept. of Nuclear and Quantum Engineering, Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

    2016-06-15

    A miniature X-ray tube based on a carbon-nanotube electron emitter has been employed for the application to a dental radiography. The miniature X-ray tube has an outer diameter of 7 mm and a length of 47 mm. The miniature X-ray tube is operated in a negative high-voltage mode in which the X-ray target is electrically grounded. In addition, X-rays are generated only to the teeth directions using a collimator while X-rays generated to other directions are shielded. Hence, the X-ray tube can be safely inserted into a human mouth. Using the intra-oral X-ray tube, a dental radiography is demonstrated where the positions of an X-ray source and a sensor are reversed compared with a conventional dental radiography system. X-ray images of five neighboring teeth are obtained and, furthermore, both left and right molar images are achieved by a single X-ray shot of the miniature X-ray tube.

  11. Near-net shape manufacturing of miniature spur gears by wire spark erosion machining

    CERN Document Server

    Gupta, Kapil

    2016-01-01

    This work describes an experimental investigation with the aim to evaluate and establish wire spark erosion machining (WSEM) as a viable alternative for high quality miniature gear manufacturing. External spur type miniature brass (ASTM 858) gears with 12 teeth, 9.8 mm outside diameter and 5 mm face width were manufactured by WSEM. The research work was accomplished in four distinct experimental stages viz., preliminary, pilot, main and confirmation. The aim, scope and findings of each stage are progressively presented and discussed. In essence, the investigation found that it was possible to manufacture miniature gears to high quality by using WSEM. Gears up to DIN 5 quality with a good surface finish (1.2 µm average roughness) and satisfactory surface integrity were achieved. The results suggest that WSEM should be considered a viable alternative to conventional miniature gear manufacturing techniques and that in some instances it may even be superior. This work will prove useful to researchers and profess...

  12. Technologies for highly miniaturized autonomous sensor networks

    NARCIS (Netherlands)

    Baert, K.; Gyselinckx, B.; Torfs, T.; Leonov, V.; Yazicioglu, F.; Brebels, S.; Donnay, S.; Vanfleteren, J.; Beyne, E.; Hoof, C. van

    2006-01-01

    Recent results of the autonomous sensor research program HUMAN++ will be summarized in this paper. The research program aims to achieve highly miniaturized and (nearly) autonomous sensor systems that assist our health and comfort. Although the application examples are dedicated to human

  13. Miniaturized measurement system for ammonia in air

    NARCIS (Netherlands)

    Timmer, B.H.; van Delft, K.M.; Otjes, R.P.; Olthuis, Wouter; van den Berg, Albert

    2004-01-01

    The development of a miniaturized ammonia sensor made using microsystem technology is described. Gas is sampled in a sampler comprising two opposite channels separated by a gas permeable, water repellent polypropylene membrane. Subsequently, the acid sample solution is pumped into a selector where

  14. Design and analysis of miniature tri-axial fluxgate magnetometer

    Science.gov (United States)

    Zhi, Menghui; Tang, Liang; Qiao, Donghai

    2017-02-01

    The detection technology of weak magnetic field is widely used in Earth resource survey and geomagnetic navigation. Useful magnetic field information can be obtained by processing and analyzing the measurement data from magnetic sensors. A miniature tri-axial fluxgate magnetometer is proposed in this paper. This miniature tri-axial fluxgate magnetometer with ring-core structure has a dynamic range of the Earth’s field ±65,000 nT, resolution of several nT. It has three independent parts placed in three perpendicular planes for measuring three orthogonal magnetic field components, respectively. A field-programmable gate array (FPGA) is used to generate stimulation signal, analog-to-digital (A/D) convertor control signal, and feedback digital-to-analog (D/A) control signal. Design and analysis details are given to improve the dynamic range, sensitivity, resolution, and linearity. Our prototype was measured and compared with a commercial standard Magson fluxgate magnetometer as a reference. The results show that our miniature fluxgate magnetometer can follow the Magson’s change trend well. When used as a magnetic compass, our prototype only has ± 0.3∘ deviation compared with standard magnetic compass.

  15. Miniaturized Charpy test for reactor pressure vessel embrittlement characterization

    Energy Technology Data Exchange (ETDEWEB)

    Manahan, M.P. Sr. [MPM Research and Consulting, Lemont, PA (United States)

    1999-10-01

    Modifications were made to a conventional Charpy machine to accommodate the miniaturized Charpy V-Notch (MCVN) specimens which were fabricated from an archived reactor pressure vessel (RPV) steel. Over 100 dynamic MCVN tests were performed and compared to the results from conventional Charpy V-Notch (CVN) tests to demonstrate the efficacy of the miniature specimen test. The optimized sidegrooved MCVN specimens exhibit transitional fracture behavior over essentially the same temperature range as the CVN specimens which indicates that the stress fields in the MCVN specimens reasonably simulate those of the CVN specimens and this fact has been observed in finite element calculations. This result demonstrates a significant breakthrough since it is now possible to measure the ductile-brittle transition temperature (DBTT) using miniature specimens with only small correction factors, and for some materials as in the present study, without the need for any correction factor at all. This development simplifies data interpretation and will facilitate future regulatory acceptance. The non-sidegrooved specimens yield energy-temperature data which is significantly shifted downward in temperature (non-conservative) as a result of the loss of constraint which accompanies size reduction.

  16. SMARBot: a modular miniature mobile robot platform

    Science.gov (United States)

    Meng, Yan; Johnson, Kerry; Simms, Brian; Conforth, Matthew

    2008-04-01

    Miniature robots have many advantages over their larger counterparts, such as low cost, low power, and easy to build a large scale team for complex tasks. Heterogeneous multi miniature robots could provide powerful situation awareness capability due to different locomotion capabilities and sensor information. However, it would be expensive and time consuming to develop specific embedded system for different type of robots. In this paper, we propose a generic modular embedded system architecture called SMARbot (Stevens Modular Autonomous Robot), which consists of a set of hardware and software modules that can be configured to construct various types of robot systems. These modules include a high performance microprocessor, a reconfigurable hardware component, wireless communication, and diverse sensor and actuator interfaces. The design of all the modules in electrical subsystem, the selection criteria for module components, and the real-time operating system are described. Some proofs of concept experimental results are also presented.

  17. A miniature spark counter for public communication and education

    International Nuclear Information System (INIS)

    Mao, C.H.; Weng, P.S.

    1987-01-01

    The fabrication of a miniature spark counter for public communication and education using naturally occurring radon as a radioactive source without involving any man-made radioactivity is described. The battery-powered miniature spark counter weighs 2.07 kg with a volume of 4.844 x 10/sup -4/ m/sup 3/. The circuitry consists of seven major components: timer, high-voltage power supply, attenuator, noninverting amplifier, low-pass filter, one-shot generator, and counter. Cellulose nitrate films irradiated with alpha particles from radon emanating from soil were etched and counted. The visible sparks during counting are rather heuristic, which can be used to demonstrate naturally occurring radioactivity in classrooms or showplaces

  18. Lobar holoprosencephaly in a Miniature Schnauzer with hypodipsic hypernatremia.

    Science.gov (United States)

    Sullivan, Stacey A; Harmon, Barry G; Purinton, P Thomas; Greene, Craig E; Glerum, Leigh E

    2003-12-15

    A 9-month-old male Miniature Schnauzer was examined because of a lifelong history of behavioral abnormalities, including hypodipsia. Diagnostic evaluation revealed marked hypernatremia and a single forebrain ventricle. The behavioral abnormalities did not resolve with correction of the hypernatremia, and the dog was euthanatized. At necropsy, midline forebrain structures were absent or reduced in size, and normally paired forebrain structures were incompletely separated. Findings were diagnostic for holoprosencephaly, a potentially genetic disorder and the likely cause of the hypodipsia. Similar evaluation of affected Miniature Schnauzer dogs may reveal whether holoprosencephaly routinely underlies the thirst deficiency that may be seen in dogs of this breed.

  19. Miniature Sensor for Aerosol Mass Measurements, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This SBIR project seeks to develop a miniature sensor for mass measurement of size-classified aerosols. A cascade impactor will be used to classify aerosol sample...

  20. Miniaturized radiation detector with custom synthesized diamond crystal as sensor

    International Nuclear Information System (INIS)

    Grobbelaar, J.H.; Burns, R.C.; Nam, T.L.; Keddy, R.J.

    1991-01-01

    A miniaturized detector consisting of three custom built hybrid circuits, a counter and a miniature high voltage power supply was designed to operate with custom synthesized Type Ib diamond crystals as sensors. Thick-film technology was incorporated in the circuit design. With a crystal having a volume of approximately 10 mm 3 and containing approximately 60 ppm paramagnetic nitrogen, the detector was capable of measuring γ-ray dose-rates as low as 7.5 μ Gy h -1 . The response characteristic was linear up to 1 cGy h -1 . (orig.)

  1. Fabrication of miniaturized electrostatic deflectors using LIGA

    International Nuclear Information System (INIS)

    Jackson, K.H.; Khan-Malek, C.; Muray, L.P.

    1997-01-01

    Miniaturized electron beam columns (open-quotes microcolumnsclose quotes) have been demonstrated to be suitable candidates for scanning electron microscopy (SEM), e-beam lithography and other high resolution, low voltage applications. In the present technology, microcolumns consist of open-quotes selectively scaledclose quotes micro-sized lenses and apertures, fabricated from silicon membranes with e-beam lithography, reactive ion beam etching and other semiconductor thin-film techniques. These miniaturized electron-optical elements provide significant advantages over conventional optics in performance and ease of fabrication. Since lens aberrations scale roughly with size, it is possible to fabricate simple microcolumns with extremely high brightness sources and electrostatic objective lenses, with resolution and beam current comparable to conventional e-beam columns. Moreover since microcolumns typically operate at low voltages (1 KeV), the proximity effects encountered in e-beam lithography become negligible. For high throughput applications, batch fabrication methods may be used to build large parallel arrays of microcolumns. To date, the best reported performance with a 1 keV cold field emission cathode, is 30 nm resolution at a working distance of 2mm in a 3.5mm column. Fabrication of the microcolumn deflector and stigmator, however, have remained beyond the capabilities of conventional machining operations and semiconductor processing technology. This work examines the LIGA process as a superior alternative to fabrication of the deflectors, especially in terms of degree of miniaturization, dimensional control, placement accuracy, run-out, facet smoothness and choice of suitable materials. LIGA is a combination of deep X-ray lithography, electroplating, and injection molding processes which allow the fabrication of microstructures

  2. Focal Segmental Glomerulosclerosis in Related Miniature Schnauzer Dogs.

    Science.gov (United States)

    Yau, Wilson; Mausbach, Lisa; Littman, Meryl P; Cianciolo, Rachel E; Brown, Cathy A

    2018-03-01

    Focal segmental glomerulosclerosis (FSGS) recently has been recognized as a common cause of proteinuria in dogs in general, and in Miniature Schnauzer dogs in particular. This study describes the morphologic features present in the kidneys of 8 related proteinuric Miniature Schnauzer dogs. The FSGS, characterized by solidification of portions of the capillary tuft, affected 32% to 49% of examined glomeruli in these dogs. Synechiae, often accompanied by hyalinosis, were present in 13% to 54% of glomeruli and were more prevalent in older dogs. Seven of 8 dogs had arteriolar hyalinosis. Ultrastructurally, all dogs had evidence of a podocytopathy in the absence of electron-dense deposits, glomerular basement membrane splitting, or fibrils. All dogs had multifocal to extensive podocyte foot process effacement. Other podocyte changes included microvillous transformation, the presence of vacuoles or protein resorption droplets, cytoplasmic electron-dense aggregates, and occasional binucleation. Variable amounts of intraglomerular lipid were present in all dogs. All dogs were proteinuric, with measured values for the urine protein-to-creatinine ratio ranging from 1.2 to 6.5. Azotemia was mild to absent and dogs were euthanatized at 5.1 to 14 years of age, in all cases due to nonrenal diseases. The underlying cause of FSGS in these Miniature Schnauzer dogs has yet to be determined, but contributors likely include genetic podocytopathy, lipid abnormalities, and glomerular hypertension.

  3. Optimal and Miniaturized Strongly Coupled Magnetic Resonant Systems

    Science.gov (United States)

    Hu, Hao

    Wireless power transfer (WPT) technologies for communication and recharging devices have recently attracted significant research attention. Conventional WPT systems based either on far-field or near-field coupling cannot provide simultaneously high efficiency and long transfer range. The Strongly Coupled Magnetic Resonance (SCMR) method was introduced recently, and it offers the possibility of transferring power with high efficiency over longer distances. Previous SCMR research has only focused on how to improve its efficiency and range through different methods. However, the study of optimal and miniaturized designs has been limited. In addition, no multiband and broadband SCMR WPT systems have been developed and traditional SCMR systems exhibit narrowband efficiency thereby imposing strict limitations on simultaneous wireless transmission of information and power, which is important for battery-less sensors. Therefore, new SCMR systems that are optimally designed and miniaturized in size will significantly enhance various technologies in many applications. The optimal and miniaturized SCMR systems are studied here. First, analytical models of the Conformal SCMR (CSCMR) system and thorough analysis and design methodology have been presented. This analysis specifically leads to the identification of the optimal design parameters, and predicts the performance of the designed CSCMR system. Second, optimal multiband and broadband CSCMR systems are designed. Two-band, three-band, and four-band CSCMR systems are designed and validated using simulations and measurements. Novel broadband CSCMR systems are also analyzed, designed, simulated and measured. The proposed broadband CSCMR system achieved more than 7 times larger bandwidth compared to the traditional SCMR system at the same frequency. Miniaturization methods of SCMR systems are also explored. Specifically, methods that use printable CSCMR with large capacitors, novel topologies including meandered, SRRs, and

  4. Spontaneous acute spinal subdural hematoma: spontaneous recovery from severe paraparesis--case report and review.

    Science.gov (United States)

    Payer, Michael; Agosti, Reto

    2010-11-01

    Spontaneous idiopathic acute spinal subdural hematomas are highly exceptional. Neurological symptoms are usually severe, and rapid diagnosis with MRI is mandatory. Surgical evacuation has frequently been used therapeutically; however, spontaneous recovery in mild cases has also been reported. We present a case of spontaneous recovery from severe paraparesis after spontaneous acute SSDH, and review the English-speaking literature.

  5. Experimental induction of struvite uroliths in miniature schnauzer and beagle dogs.

    Science.gov (United States)

    Klausner, J S; Osborne, C A; O'Leary, T P; Muscoplat, C M; Griffith, D P

    1980-09-01

    Urease positive staphylococcal urinary tract infection was experimentally induced in 13 dogs. Eight dogs developed cystic and/or urethral struvite calculi in 2 to 8 weeks. No abnormalities in systemic cell mediated immunity were detected in dogs before or after the establishment of the urinary tract infection. Miniature schnauzers whose ancestors had developed stones seemed to be no more susceptible to experimental urinary tract infection and stone formation than miniature schnauzers or beagles whose ancestors did not develop stones.

  6. A new miniaturized negative-index meta-atom for tri-band applications

    Directory of Open Access Journals (Sweden)

    Hossain Mohammad Jakir

    2017-07-01

    Full Text Available In this paper, a miniature negative index meta-atom was designed; simulated, fabricated and measured based on parallel incidence of electromagnetic wave that can maintain a tri-band applications in microwave spectra. Compare to the other multi-band conventional metamaterial, the proposed meta-atom structure allows miniaturization factor and follows better effective medium ratio (EMR. Finite-integration technique (FIT based computer simulation technology (CST electromagnetic simulator was adopted to examine the design of the meta-atom. It exhibits tri-band response in conjunction with backward wave property over a certain frequency band in the microwave regime. Furthermore, the effective medium ratio is considerably improved compared to previously reported metamaterial. Moreover, few parametric analyses were done with the meta-atom. The size, scattering parameters and effective medium parameters of the proposed negative index miniaturized meta-atom is appropriate for tri-band applications.

  7. Miniaturization of high-energy physics detectors. Vol. 14

    International Nuclear Information System (INIS)

    Stefanini, A.

    1983-01-01

    Continued experimental research in high-energy physics requires the reduction in size and cost of the advanced technical equipment involved. A new technology is rapidly evolving that promises to replace today's massive high-energy physics instruments--which may be composed of several thousand tons of sensitive parts--with miniaturized equivalents. Smaller, less expensive apparatus would create more opportunities for research worldwide, and many types of experiments now considered impractical could then be carried out. Scientists and engineers from many countries have contributed to this volume to provide a broad panorama of the new miniaturization technology in high-energy physics. They describe a wide range of new instruments and their applications, discuss limitations and technological problems, and explore the connections between technology and progress in the field of high-energy physics

  8. A Miniature Coupled Bistable Vibration Energy Harvester

    International Nuclear Information System (INIS)

    Zhu, D; Arthur, D C; Beeby, S P

    2014-01-01

    This paper reports the design and test of a miniature coupled bistable vibration energy harvester. Operation of a bistable structure largely depends on vibration amplitude rather than frequency, which makes it very promising for wideband vibration energy harvesting applications. A coupled bistable structure consists of a pair of mobile magnets that create two potential wells and thus the bistable phenomenon. It requires lower excitation to trigger bistable operation compared to conventional bistable structures. Based on previous research, this work focused on miniaturisation of the coupled bistable structure for energy harvesting application. The proposed bistable energy harvester is a combination of a Duffing's nonlinear structure and a linear assisting resonator. Experimental results show that the output spectrum of the miniature coupled bistable vibration energy harvester was the superposition of several spectra. It had a higher maximum output power and a much greater bandwidth compared to simply the Duffing's structure without the assisting resonator

  9. Generation of an isogenic, gene-corrected iPSC line from a symptomatic 59-year-old female patient with frontotemporal dementia caused by an R406W mutation in the microtubule associated protein tau (MAPT) gene

    DEFF Research Database (Denmark)

    Nimsanor, Natakarn; Poulsen, Ulla; Rasmussen, Mikkel A.

    2016-01-01

    pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required cell type. Furthermore, gene-editing approaches allow generating isogenic gene-corrected controls that can be used as a very specific control. Here, we report the generation......Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the MAPT (microtubule-associated protein tau) gene can cause FTDP-17, but the underlying pathomechanisms of the disease are still unknown. Induced...... of genetically corrected iPSCs from a 59-year-old female FTD-17 patient carrying an R406W mutation in the MAPT-gene....

  10. Generation of an isogenic, gene-corrected iPSC line from a symptomatic 57-year-old female patient with frontotemporal dementia caused by a P301L mutation in the microtubule associated protein tau (MAPT) gene

    DEFF Research Database (Denmark)

    Nimsanor, Natakarn; Kitiyanant, Narisorn; Poulsen, Ulla

    2016-01-01

    pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required cell type. Furthermore, gene-editing approaches allow generating isogenic gene-corrected controls that can be used as a very specific control. Here, we report the generation......Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the MAPT (microtubule-associated protein tau)-gene can cause FTDP-17, but the underlying pathomechanisms of the disease are still unknown. Induced...... of genetically corrected iPSCs from a 57-year-old female FTD-17 patient carrying an P301L mutation in the MAPT-gene....

  11. Naturalism and Mannerism in Indian Miniatures

    Science.gov (United States)

    Duran, Jane

    2001-01-01

    In this essay, the author furthers the argument that critical commentary on the Rajput and Muslim miniatures of India has focused on a rather odd use of labels and categories, perhaps to an even greater extent than has been the case with much of the rest of the criticism of the art of South Asia. She first examines the use of the term…

  12. Bend testing for miniature disks

    International Nuclear Information System (INIS)

    Huang, F.H.; Hamilton, M.L.; Wire, G.L.

    1982-01-01

    A bend test was developed to obtain ductility measurements on a large number of alloy variants being irradiated in the form of miniature disks. Experimental results were shown to be in agreement with a theoretical analysis of the bend configuration. Disk specimens fabricated from the unstrained grip ends of previously tested tensile specimens were used for calibration purposes; bend ductilities and tensile ductilities were in good agreement. The criterion for estimating ductility was judged acceptable for screening purposes

  13. Miniaturization of Fresnel lenses for solar concentration: a quantitative investigation.

    Science.gov (United States)

    Duerr, Fabian; Meuret, Youri; Thienpont, Hugo

    2010-04-20

    Sizing down the dimensions of solar concentrators for photovoltaic applications offers a number of promising advantages. It provides thinner modules and smaller solar cells, which reduces thermal issues. In this work a plane Fresnel lens design is introduced that is first analyzed with geometrical optics. Because of miniaturization, pure ray tracing may no longer be valid to determine the concentration performance. Therefore, a quantitative wave optical analysis of the miniaturization's influence on the obtained concentration performance is presented. This better quantitative understanding of the impact of diffraction in microstructured Fresnel lenses might help to optimize the design of several applications in nonimaging optics.

  14. Evaluation of a miniature magnetostrictive actuator using Galfenol under tensile stress

    International Nuclear Information System (INIS)

    Ueno, Toshiyuki; Miura, Hidemitsu; Yamada, Sotoshi

    2011-01-01

    We are, at present, developing miniature actuators using an iron-gallium alloy (Galfenol). Galfenol is an iron-based magnetostrictive material with magnetostriction exceeding 200 ppm, Young's modulus of 70 GPa and a high relative permeability (>100). The advantages of an actuator using this material are capability of miniaturization, stability against external force, low voltage driving and high power. In this study, a miniature vibrator using an E core of Galfenol under tensile stress up to 20 MPa was investigated. The vibrator did not fracture and maintained the magnetostriction even under a high tensile stress. In addition, the resonance frequency, unchanged under the tensile stress, was lower than the cutoff frequency, hence the vibrator can be driven with a low voltage even in resonance driving. The temperature rise in resonance driving was low and creep was not observed in resonance driving under tensile stress. The vibrator will be applicable in flat panel or bone conductive speakers.

  15. Evaluation of a miniature magnetostrictive actuator using Galfenol under tensile stress

    Science.gov (United States)

    Ueno, Toshiyuki; Miura, Hidemitsu; Yamada, Sotoshi

    2011-02-01

    We are, at present, developing miniature actuators using an iron-gallium alloy (Galfenol). Galfenol is an iron-based magnetostrictive material with magnetostriction exceeding 200 ppm, Young's modulus of 70 GPa and a high relative permeability (>100). The advantages of an actuator using this material are capability of miniaturization, stability against external force, low voltage driving and high power. In this study, a miniature vibrator using an E core of Galfenol under tensile stress up to 20 MPa was investigated. The vibrator did not fracture and maintained the magnetostriction even under a high tensile stress. In addition, the resonance frequency, unchanged under the tensile stress, was lower than the cutoff frequency, hence the vibrator can be driven with a low voltage even in resonance driving. The temperature rise in resonance driving was low and creep was not observed in resonance driving under tensile stress. The vibrator will be applicable in flat panel or bone conductive speakers.

  16. Nanoparticle separation with a miniaturized asymmetrical flow field-flow fractionation cartridge

    Science.gov (United States)

    Müller, David; Cattaneo, Stefano; Meier, Florian; Welz, Roland; deMello, Andrew

    2015-07-01

    Asymmetrical Flow Field-Flow Fractionation (AF4) is a separation technique applicable to particles over a wide size range. Despite the many advantages of AF4, its adoption in routine particle analysis is somewhat limited by the large footprint of currently available separation cartridges, extended analysis times and significant solvent consumption. To address these issues, we describe the fabrication and characterization of miniaturized AF4 cartridges. Key features of the scale-down platform include simplified cartridge and reagent handling, reduced analysis costs and higher throughput capacities. The separation performance of the miniaturized cartridge is assessed using certified gold and silver nanoparticle standards. Analysis of gold nanoparticle populations indicates shorter analysis times and increased sensitivity compared to conventional AF4 separation schemes. Moreover, nanoparticulate titanium dioxide populations exhibiting broad size distributions are analyzed in a rapid and efficient manner. Finally, the repeatability and reproducibility of the miniaturized platform are investigated with respect to analysis time and separation efficiency.

  17. Miniature scientific-grade magnetic sensors for CubeSats

    Science.gov (United States)

    Pronenko, Vira; Belyayev, Serhiy

    2016-07-01

    Micro- and nanosatellites have become more attractive due to their low development and launch cost. A class of nanosatellites defined by the CubeSat standard allows standardizing CubeSat preparation and launch, thus making the projects more affordable. Because of the complexity of sensors miniaturization to install them onboard CubeSat, the majority of CubeSat launches are aimed the technology demonstration or education missions. The scientific success of CubeSat mission depends on the sensors quality. In spite that the sensitivity of the magnetic sensors strongly depends on their size, the recent development in this branch allows us to propose tiny but sensitive both AC and DC magnetometers. The goal of the present report is to introduce the new design of miniature three-component sensors for measurement of vector magnetic fields - for quasi-stationary and slowly fluctuating - flux-gate magnetometer (FGM) - and for alternative ones - search-coil magnetometer (SCM). In order to create magnetometers with the really highest possible level of parameters, a set of scientific and technological problems, mostly aimed at the sensor construction improvement, was solved. The most important parameter characterizing magnetometer quality is its own magnetic noise level (NL). The analysis of the NL influencing factors is made and the ways to decrease it are discussed in the report. Construction details and technical specifications of miniature but sensitive FGM and SCM for the CubeSat mission are presented. This work is supported by EC Framework 7 funded project 607197.

  18. Miniaturized chromatographic radiochemical procedure for 131I - MIBG

    International Nuclear Information System (INIS)

    Barboza, M.F. de; Pereira, N.S. de; Colturato, M.T.; Silva, C.P.G. da.

    1989-12-01

    Different solvents were used in paper chromatographic methods to obtain the best system in routine radiochemical control for 131 I-MIBG produced at IPEN-CNEN/SP. The dates were compared with those obtained with eletrophoresis method in buffer acetate, pH=4.5, 350V, during 40 minutes. The stability of the labeled compound store under 4 0 C was studied during 15 days. Miniaturized chromatographic procedures were established using Whatman 3MM (8x1cm) and n-butanol-:acetic acid: water (S:2:1) as a solvent. the Rf values were: 0.3 (I - ) and 1.0 (MIBG). The radiochemical purity was 99.3 and 99.2% (first day) obtained with eletrophoresis and miniaturized chromatographic procedures, respectively and, 84.7% after 15 days of its preparation. It is a rapid, practical and reproductive method. (author) [pt

  19. Miniaturized and reconfigurable notch antenna based on a BST ferroelectric thin film

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Hung Viet [Institut d' Electronique et de Télécommunications de Rennes (IETR), IUT Saint-Brieuc, Université de Rennes 1, 22004 Saint-Brieuc (France); CEA-LETI, Minatec, 17 avenue des Martyrs, 38054 Grenoble Cedex 9 (France); Benzerga, Ratiba, E-mail: ratiba.benzerga@univ-rennes1.fr [Institut d' Electronique et de Télécommunications de Rennes (IETR), IUT Saint-Brieuc, Université de Rennes 1, 22004 Saint-Brieuc (France); Borderon, Caroline [IETR, Université de Nantes, 2 rue de la Houssinière, 44322 Nantes (France); Delaveaud, Christophe [CEA-LETI, Minatec, 17 avenue des Martyrs, 38054 Grenoble Cedex 9 (France); Sharaiha, Ala [Institut d' Electronique et de Télécommunications de Rennes (IETR), IUT Saint-Brieuc, Université de Rennes 1, 22004 Saint-Brieuc (France); Renoud, Raphael [IETR, Université de Nantes, 2 rue de la Houssinière, 44322 Nantes (France); Paven, Claire Le [Institut d' Electronique et de Télécommunications de Rennes (IETR), IUT Saint-Brieuc, Université de Rennes 1, 22004 Saint-Brieuc (France); Pavy, Sabrina; Nadaud, Kevin; Gundel, Hartmut W. [IETR, Université de Nantes, 2 rue de la Houssinière, 44322 Nantes (France)

    2015-07-15

    Highlights: • A miniature and agile antenna based on a BST MIM capacitor is simulated and made. • Mn{sup 2+} doped BST thin films are synthesized by chemical deposition and spin coating. • Permittivity and losses of the BST thin film are respectively 225 and 0.02 at 1 GHz. • A miniaturization rate of 70% is obtained with a MIM capacitance of 3.7 pF. • A frequency tunability of 14.5% and a tunability performance of 0.04 are measured. - Abstract: This work deals with the design, realization and characterization of a miniature and frequency agile antenna based on a ferroelectric Ba{sub 0,80}Sr{sub 0,20}TiO{sub 3} thin film. The notch antenna is loaded with a variable metal/insulator/metal (MIM) capacitor and is achieved by a monolithic method. The MIM capacitance is 3.7 pF, which results in a resonant frequency of 670 MHz compared to 2.25 GHz for the unloaded simulated antenna; the resulting miniaturization rate is 70%. The characterization of the antenna prototype shows a frequency tunable rate of 14.5% under an electric field of 375 kV/cm, with a tunability performance η = 0.04.

  20. Miniature X-ray Tube for Electric Brachytherapy using Carbon Nanotube Field Emitter

    International Nuclear Information System (INIS)

    Heo, Sung Hwan; Kim, Hyun Jin; Ha, Jun Mok; Cho, Sung Oh

    2011-01-01

    An electric brachytherapy using a miniature x-ray tube has a major advantage to reduce the x-ray exposure of human body during the cancer radiation therapy by optimal positioning of x-ray radiation source and treatment objectives. In the view of a smaller electronic x-ray source, the CNT field emitter based xray tube can be more minimized than thermionic filament emitter based one because of a simple power supplier connection of cold field emission in diode type as well as a higher electron emission brightness of CNT. This abstract is for introducing the design of a prototype CNT field emitter based miniature x-ray tube. We have vacuum sealed CNT miniature x-ray tube with 7∼10 mm diameter, and characteristics of electron emission and x-ray transportation using MCNP5 code are surveyed

  1. A miniaturized plastic dilution refrigerator

    International Nuclear Information System (INIS)

    Bindilatti, V.; Oliveira, N.F.Jr.; Martin, R.V.; Frossati, G.

    1996-01-01

    We have built and tested a miniaturized dilution refrigerator, completely contained (still, heat exchanger and mixing chamber) inside a plastic (PVC) tube of 10 mm diameter and 170 mm length. With a 25 cm 2 CuNi heat exchanger, it reached temperatures below 50 mK, for circulation rates below 70 μmol/s. The cooling power at 100 mK and 63 μmol/s was 45 μW. The experimental space could accommodate samples up to 6 mm in diameter. (author)

  2. Differential control of central cardiorespiratory interactions by hypercapnia and the effect of prenatal nicotine.

    Science.gov (United States)

    Huang, Zheng-Gui; Griffioen, Kathleen J S; Wang, Xin; Dergacheva, Olga; Kamendi, Harriet; Gorini, Christopher; Bouairi, Euguenia; Mendelowitz, David

    2006-01-04

    Hypercapnia evokes a strong cardiorespiratory response including gasping and a pronounced bradycardia; however, the mechanism responsible for these survival responses initiated in the brainstem is unknown. To examine the effects of hypercapnia on the central cardiorespiratory network, we used an in vitro medullary slice that allows simultaneous examination of rhythmic respiratory-related activity and inhibitory synaptic neurotransmission to cardioinhibitory vagal neurons (CVNs). Hypercapnia differentially modulated inhibitory neurotransmission to CVNs; whereas hypercapnia selectively depressed spontaneous glycinergic IPSCs in CVNs without altering respiratory-related increases in glycinergic neurotransmission, it decreased both spontaneous and inspiratory-associated GABAergic IPSCs. Because maternal smoking is the highest risk factor for sudden infant death syndrome (SIDS) and prenatal nicotine exposure is proposed to be the link between maternal smoking and SIDS, we examined the cardiorespiratory responses to hypercapnia in animals exposed to nicotine in the prenatal and perinatal period. In animals exposed to prenatal nicotine, hypercapnia evoked an exaggerated depression of GABAergic IPSCs in CVNs with no significant change in glycinergic neurotransmission. Hypercapnia altered inhibitory neurotransmission to CVNs at both presynaptic and postsynaptic sites. Although the results obtained in this study in vitro cannot be extrapolated with certainty to in vivo responses, the results of this study provide a likely neurochemical mechanism for hypercapnia-evoked bradycardia and the dysregulation of this response with exposure to prenatal nicotine, creating a higher risk for SIDS.

  3. A molecular diagnostic test for persistent Müllerian duct syndrome in miniature schnauzer dogs.

    Science.gov (United States)

    Pujar, S; Meyers-Wallen, V N

    2009-01-01

    In persistent Müllerian duct syndrome (PMDS), Müllerian ducts fail to regress in males during sexual differentiation. In the canine miniature schnauzer model, PMDS is caused by a C to T transition in exon 3 of the Müllerian inhibiting substance type II receptor (MISRII), which introduces a DdeI restriction site. Here we report a molecular diagnostic test for PMDS in the miniature schnauzer to identify affected dogs and carriers. As our test results suggest that the mutation is identical by descent in affected dogs of this breed, the test could be used to eliminate this mutation from the miniature schnauzer breed worldwide.

  4. Maxillary bone epithelial cyst in an adult miniature schnauzer.

    Science.gov (United States)

    Lin, Chung-Tien; Tasi, Wen-Chih; Hu, Chun-Kun; Lin, Nien-Ting; Huang, Pei-Yun; Yeh, Lih-Seng

    2008-09-01

    Maxillary bone epithelial cyst is rare in dogs. A 5-year-old, spayed female miniature schnauzer developed a swelling below the nasal canthus of left eye. Plain radiograph demonstrated a 1.5 cm diameter of radiolucent lesion on the maxillary bone anteroventral to the eye, and contrast dacryocystorhinography confirmed an obstructed nasolarcrimal duct. The swelling showed poor response to antibiotic treatment but responded well to oral prednisolone. Exploratory surgery revealed a cyst-like structure filled with brown serous fluid. Histopathological examination of the removed cyst revealed a double cuboidal epithelial cyst. The dog recovered rapidly after surgery, and the swelling had not recurred for a 36-month follow-up. It is the first case of periorbital bone epithelial cyst reported in an adult miniature schnauzer.

  5. Miniaturizing EM Sample Preparation: Opportunities, Challenges, and "Visual Proteomics".

    Science.gov (United States)

    Arnold, Stefan A; Müller, Shirley A; Schmidli, Claudio; Syntychaki, Anastasia; Rima, Luca; Chami, Mohamed; Stahlberg, Henning; Goldie, Kenneth N; Braun, Thomas

    2018-03-01

    This review compares and discusses conventional versus miniaturized specimen preparation methods for transmission electron microscopy (TEM). The progress brought by direct electron detector cameras, software developments and automation have transformed transmission cryo-electron microscopy (cryo-EM) and made it an invaluable high-resolution structural analysis tool. In contrast, EM specimen preparation has seen very little progress in the last decades and is now one of the main bottlenecks in cryo-EM. Here, we discuss the challenges faced by specimen preparation for single particle EM, highlight current developments, and show the opportunities resulting from the advanced miniaturized and microfluidic sample grid preparation methods described, such as visual proteomics and time-resolved cryo-EM studies. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Miniature Reaction Wheel for Small Satellite Control, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The overall goal of this project is to design, develop, demonstrate, and deliver a miniature, high torque, low-vibration reaction wheel for use on small satellites....

  7. Miniature, mobile X-ray computed radiography system

    Science.gov (United States)

    Watson, Scott A; Rose, Evan A

    2017-03-07

    A miniature, portable x-ray system may be configured to scan images stored on a phosphor. A flash circuit may be configured to project red light onto a phosphor and receive blue light from the phosphor. A digital monochrome camera may be configured to receive the blue light to capture an article near the phosphor.

  8. The MIT miniaturized disk bend test

    International Nuclear Information System (INIS)

    Harling, O.K.; Lee, M.; Sohn, D.S.; Kohse, G.; Lau, C.W.

    1983-01-01

    A miniaturized disk bend test (MDBT) using transmission electron microscopy specimens for the determination of various mechanical properties is being developed at MIT. Recent progress in obtaining strengths and ductilities of highly irradiated metal alloys is reviewed. Possibilities exist for applying the MDBT approach to the determination of other mechanical properties. Progress in fatigue testing and in determination of the ductile-to-brittle transition temperature is reviewed briefly

  9. Miniature magnetic fluid seal working in liquid environments

    Science.gov (United States)

    Mitamura, Yoshinori; Durst, Christopher A.

    2017-06-01

    This study was carried out to develop a miniature magnetic fluid (MF) seal working in a liquid environment. The miniature MF seal is intended for use in a catheter blood pump. The requirements for the MF seal included a size of less than Ø4×4.5 mm, shaft diameter of 1 mm, sealing pressure of 200 mmHg, shaft speed of up to 40000 rpm, and life of one month. The miniature MF seal was composed of an NdFeB magnet (Ø4×Ø2×1) sandwiched between two pole pieces (Ø4×Ø1.1×0.5). A shield (Ø4×Ø1.2×1.5) was placed on the pole piece facing the liquid to minimize the influence of pump flow on the MF. The seal was installed on a Ø1 shaft. A seal was formed by injecting MF (Ms: 47.8 kA/m and η: 0.5 Pa·sec) into the gap between the pole pieces and the shaft. Total volume of the MF seal was 44 μL. A sealing pressure of 370 mmHg was obtained at motor speeds of 0-40,000 rpm. The seal remained perfect for 10 days in saline under the condition of a pump flow of 1.5 L/min (The test was terminated in accordance with plans). The seal remained intact after ethylene oxide sterilization during which the seal was exposed to high pressures. In conclusion, the newly developed MF seal will be useful for a catheter pump.

  10. Spontaneous external gallbladder perforation

    International Nuclear Information System (INIS)

    Noeldge, G.; Wimmer, B.; Kirchner, R.

    1981-01-01

    Spontaneous perforation of the gallbladder is one complication of cholelithiasis. There is a greater occurence of free perforation in the peritoneal cavity with bilary pertonitis, followed by the perforation into the stomach, small intestine and colon. A single case of the nowadays rare spontaneous perforation in and through the abdominal wall will be reported. Spontaneous gallbladder perforation appears nearly asymptomatic in its clinical course because of absent biliary peritonitis. (orig.) [de

  11. Pinching evidences in a miniature plasma focus with fast pseudospark switch

    International Nuclear Information System (INIS)

    Hassan, S M; Zhang, T; Patran, A; Rawat, R S; Springham, S V; Tan, T L; Wong, D; Wang, W; Lee, S; Gribkov, V A; Mohanty, S R; Lee, P

    2006-01-01

    We report the observations of pinching in a miniature plasma focus (PF) (58-160 J) operated in repetitive mode using fast pseudospark switch (PSS). The size of the device, which includes the capacitor bank, PSS and the focus chamber, is of the order of 22 cm x 22 cm x 38 cm. Several diagnostic tools, the gated imager, streak camera, current and voltage probe, are employed simultaneously to confirm the occurrence of pinching in this fast miniature PF device. The device is optimized for operation in neon and hydrogen as the working gas. The best focus formation was obtained at pressures between 0.5 to 8.0 mbar for neon and between 7.0 to 15.0 mbar for hydrogen. When the system was operated at 100 J with hydrogen as the filling gas, the typical dip in the current derivative signal and the typical peak in the voltage signal associated with pinch compression, are observed to be most intense indicating efficient pinching in the miniature PF device

  12. Current applications of miniaturized chromatographic and electrophoretic techniques in drug analysis.

    Science.gov (United States)

    Aturki, Zeineb; Rocco, Anna; Rocchi, Silvia; Fanali, Salvatore

    2014-12-01

    In the last decade, miniaturized separation techniques have become greatly popular in pharmaceutical analysis. Miniaturized separation methods are increasingly utilized in all processes of drug discovery as well as quality control of pharmaceutical preparation. The great advantages presented by the analytical miniaturized techniques, including high separation efficiency and resolution, rapid analysis and minimal consumption of reagents and samples, make them an attractive alternative to the conventional chromatographic methods for drug analysis. The purpose of this review is to give a general overview of the applicability of capillary electrophoresis (CE), capillary electrochromatography (CEC) and micro/capillary/nano-liquid chromatography (micro-LC/CLC/nano-LC) for the analysis of pharmaceutical formulations, active pharmaceutical ingredients (API), drug impurity testing, chiral drug separation, determination of drugs and metabolites in biological fluids. The results concerning the use of CEC, micro-LC, CLC, and nano-LC in the period 2009-2013, while for CE, those from 2012 up to the review draft are here summarized and some specific examples are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome.

    Science.gov (United States)

    Liu, Guang-Hui; Barkho, Basam Z; Ruiz, Sergio; Diep, Dinh; Qu, Jing; Yang, Sheng-Lian; Panopoulos, Athanasia D; Suzuki, Keiichiro; Kurian, Leo; Walsh, Christopher; Thompson, James; Boue, Stephanie; Fung, Ho Lim; Sancho-Martinez, Ignacio; Zhang, Kun; Yates, John; Izpisua Belmonte, Juan Carlos

    2011-04-14

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature ageing disease, characterized by premature arteriosclerosis and degeneration of vascular smooth muscle cells (SMCs). HGPS is caused by a single point mutation in the lamin A (LMNA) gene, resulting in the generation of progerin, a truncated splicing mutant of lamin A. Accumulation of progerin leads to various ageing-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature ageing. Upon differentiation of HGPS-iPSCs, progerin and its ageing-associated phenotypic consequences are restored. Specifically, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescence phenotypes associated with vascular ageing. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs, also known as PRKDC) as a downstream target of progerin. The absence of nuclear DNAPK holoenzyme correlates with premature as well as physiological ageing. Because progerin also accumulates during physiological ageing, our results provide an in vitro iPSC-based model to study the pathogenesis of human premature and physiological vascular ageing.

  14. A Miniature Data Repository on a Raspberry Pi

    NARCIS (Netherlands)

    Samourkasidis, Argyrios; Athanasiadis, Ioannis N.

    2017-01-01

    This work demonstrates a low-cost, miniature data repository proof-of-concept. Such a system needs to be resilient to power and network failures, and expose adequate processing power for persistent, long-term storage. Additional services are required for interoperable data sharing and visualization.

  15. Lightweight, Miniature Inertial Measurement System

    Science.gov (United States)

    Tang, Liang; Crassidis, Agamemnon

    2012-01-01

    A miniature, lighter-weight, and highly accurate inertial navigation system (INS) is coupled with GPS receivers to provide stable and highly accurate positioning, attitude, and inertial measurements while being subjected to highly dynamic maneuvers. In contrast to conventional methods that use extensive, groundbased, real-time tracking and control units that are expensive, large, and require excessive amounts of power to operate, this method focuses on the development of an estimator that makes use of a low-cost, miniature accelerometer array fused with traditional measurement systems and GPS. Through the use of a position tracking estimation algorithm, onboard accelerometers are numerically integrated and transformed using attitude information to obtain an estimate of position in the inertial frame. Position and velocity estimates are subject to drift due to accelerometer sensor bias and high vibration over time, and so require the integration with GPS information using a Kalman filter to provide highly accurate and reliable inertial tracking estimations. The method implemented here uses the local gravitational field vector. Upon determining the location of the local gravitational field vector relative to two consecutive sensors, the orientation of the device may then be estimated, and the attitude determined. Improved attitude estimates further enhance the inertial position estimates. The device can be powered either by batteries, or by the power source onboard its target platforms. A DB9 port provides the I/O to external systems, and the device is designed to be mounted in a waterproof case for all-weather conditions.

  16. Flight experience with lightweight, low-power miniaturized instrumentation systems

    Science.gov (United States)

    Hamory, Philip J.; Murray, James E.

    1992-01-01

    Engineers at the NASA Dryden Flight Research Facility (NASA-Dryden) have conducted two flight research programs with lightweight, low-power miniaturized instrumentation systems built around commercial data loggers. One program quantified the performance of a radio-controlled model airplane. The other program was a laminar boundary-layer transition experiment on a manned sailplane. The purpose of this paper is to report NASA-Dryden personnel's flight experience with the miniaturized instrumentation systems used on these two programs. The paper will describe the data loggers, the sensors, and the hardware and software developed to complete the systems. The paper also describes how the systems were used and covers the challenges encountered to make them work. Examples of raw data and derived results will be shown as well. Finally, future plans for these systems will be discussed.

  17. Rad-Hard, Miniaturized, Scalable, High-Voltage Switching Module for Power Applications Rad-Hard, Miniaturized

    Science.gov (United States)

    Adell, Philippe C.; Mojarradi, Mohammad; DelCastillo, Linda Y.; Vo, Tuan A.

    2011-01-01

    A paper discusses the successful development of a miniaturized radiation hardened high-voltage switching module operating at 2.5 kV suitable for space application. The high-voltage architecture was designed, fabricated, and tested using a commercial process that uses a unique combination of 0.25 micrometer CMOS (complementary metal oxide semiconductor) transistors and high-voltage lateral DMOS (diffusion metal oxide semiconductor) device with high breakdown voltage (greater than 650 V). The high-voltage requirements are achieved by stacking a number of DMOS devices within one module, while two modules can be placed in series to achieve higher voltages. Besides the high-voltage requirements, a second generation prototype is currently being developed to provide improved switching capabilities (rise time and fall time for full range of target voltages and currents), the ability to scale the output voltage to a desired value with good accuracy (few percent) up to 10 kV, to cover a wide range of high-voltage applications. In addition, to ensure miniaturization, long life, and high reliability, the assemblies will require intensive high-voltage electrostatic modeling (optimized E-field distribution throughout the module) to complete the proposed packaging approach and test the applicability of using advanced materials in a space-like environment (temperature and pressure) to help prevent potential arcing and corona due to high field regions. Finally, a single-event effect evaluation would have to be performed and single-event mitigation methods implemented at the design and system level or developed to ensure complete radiation hardness of the module.

  18. Definition of spontaneous reconnection

    International Nuclear Information System (INIS)

    Schindler, K.

    1984-01-01

    The author discusses his view of driven versus spontaneous. There is a close link between ''spontaneous'' and ''instability.'' One of the prominent examples for instability is the thermal convection instability. Just to remind you, if you heat a fluid layer from below, it takes a certain Rayleigh number to make it unstable. Beyond the onset point you find qualitatively new features. That is called ''spontaneous,'' and this is a bit more than semantics. It's a new qualitative property that appears and it is spontaneous although we have an energy flux through the system. It's a misconception, to call this ''driven'' pointing at the energy flux through it. Of course, the convection would not exist without this energy flux. But what makes it ''spontaneous'' is that without any particular external signal, a new qualitative feature appears. And this is what is called an ''instability'' and ''spontaneous.'' From these considerations the author got a little reassured of what distinction should be made in the field of the magnetosphere. If we have a smooth energy transport into the magnetosphere and suddenly we have this qualitatively new feature (change of B-topology) coming up; then, using this terminology we don't have a choice other than calling this spontaneous or unstable, if you like. If we ''tell'' the system where it should make its neutral line and where it should make its plasmoids, then, it is driven. And this provides a very clear-cut observational distinction. The author emphasizes the difference he sees is a qualitative difference, not only a quantitative one

  19. Miniature rainbow schlieren deflectometry system for quantitative measurements in microjets and flames

    International Nuclear Information System (INIS)

    Satti, Rajani P.; Kolhe, Pankaj S.; Olcmen, Semih; Agrawal, Ajay K.

    2007-01-01

    Recent interest in small-scale flow devices has created the need for miniature instruments capable of measuring scalar flow properties with high spatial resolution. We present a miniature rainbow schlieren deflectometry system to nonintrusively obtain quantitative species concentration and temperature data across the whole field. The optical layout of the miniature system is similar to that of a macroscale system, although the field of view is smaller by an order of magnitude. Employing achromatic lenses and a CCD array together with a camera lens and extension tubes, we achieved spatial resolution down to 4 μm. Quantitative measurements required a careful evaluation of the optical components. The capability of the system is demonstrated by obtaining concentration measurements in a helium microjet (diameter, d=650 μm) and temperature and concentration measurements in a hydrogen jet diffusion flame from a microinjector(d=50 μm). Further, the flow field of underexpanded nitrogen jets is visualized to reveal details of the shock structures existing downstream of the jet exit

  20. Ambiguous genitalia in a fertile, unilaterally cryptorchid male miniature schnauzer dog.

    Science.gov (United States)

    Breshears, M A; Peters, J L

    2011-09-01

    A 7-year-old male miniature schnauzer dog with unilateral cryptorchidism was presented for elective orchiectomy. Surgery to remove the cryptorchid testis revealed a fully formed uterus with horns attached to both testis and the body and cervix terminating at the prostate gland. The gross and microscopic diagnosis for the genital tract was persistent Müllerian duct syndrome with unilateral cryptorchidism. Additional associated lesions included cystic endometrial hyperplasia and a solitary, intratubular seminoma within the undescended testis. Persistent Müllerian duct syndrome is rare among domestic animals but is more common in miniature schnauzer dogs because of inheritance as an autosomal recessive trait.

  1. Hereditary esophageal dysfunction in the Miniature Schnauzer dog.

    Science.gov (United States)

    Cox, V S; Wallace, L J; Anderson, V E; Rushmer, R A

    1980-03-01

    Miniature Schnauzers maintained in a colony for 9 years were used to study the inheritance of esophageal dysfunction (canine achalasia, megaesophagus). All dogs were evaluated radiographically, using a barium swallow contrast technique which clearly distinguished normal and affected pups. At 4 to 6 months of age, all affected dogs had recovered clinically except one, and radiographic evidence of dysfunction was markedly diminished. None of the affected dogs required a special feeding regimen. Analysis of breeding pairs revealed a ratio of 9 affected/11 normal dogs when an affected male was mated with a normal female, and a 13/3 ratio was observed when two affected dogs were mated. These ratios were compatible with a simple autosomal dominant or a 60% penetrance autosomal-recessive mode of inheritance. Outbreeding to an affected Miniature Schnauzer/Poodle crossbred dog resulted in only two of 30 affected pups, indicating a polygenic mode of inheritance in outbred populations.

  2. Digital intelligent booster for DCC miniature train networks

    Science.gov (United States)

    Ursu, M. P.; Condruz, D. A.

    2017-08-01

    Modern miniature trains are now driven by means of the DCC (Digital Command and Control) system, which allows the human operator or a personal computer to launch commands to each individual train or even to control different features of the same train. The digital command station encodes these commands and sends them to the trains by means of electrical pulses via the rails of the railway network. Due to the development of the miniature railway network, it may happen that the power requirement of the increasing number of digital locomotives, carriages and accessories exceeds the nominal output power of the digital command station. This digital intelligent booster relieves the digital command station from powering the entire railway network all by itself, and it automatically handles the multiple powered sections of the network. This electronic device is also able to detect and process short-circuits and overload conditions, without the intervention of the digital command station.

  3. Adventitious shoot regeneration from leaf explants of miniature paprika

    African Journals Online (AJOL)

    STORAGESEVER

    2010-05-10

    May 10, 2010 ... products, Capsicum spp. shows high levels of cross pollination ... Composition of a nutrient solution used for the culture of miniature paprika in the greenhouse. ... Yellow' were obtained from Seminis Korea Inc. Seeds were.

  4. Movement recognition technology as a method of assessing spontaneous general movements in high risk infants

    Directory of Open Access Journals (Sweden)

    Claire eMarcroft

    2015-01-01

    Full Text Available Preterm birth is associated with increased risks of neurological and motor impairments such as cerebral palsy. The risks are highest in those born at the lowest gestations. Early identification of those most at risk is challenging meaning that a critical window of opportunity to improve outcomes through therapy-based interventions may be missed. Clinically, the assessment of spontaneous general movements is an important tool which can be used for the prediction of movement impairments in high risk infants.Movement recognition aims to capture and analyze relevant limb movements through computerized approaches focusing on continuous, objective, and quantitative assessment. Different methods of recording and analyzing infant movements have recently been explored in high risk infants. These range from camera-based solutions to body-worn miniaturized movement sensors used to record continuous time-series data that represent the dynamics of limb movements. Various machine learning methods have been developed and applied to the analysis of the recorded movement data. This analysis has focused on the detection and classification of atypical spontaneous general movements. This paper aims to identify recent translational studies using movement recognition technology as a method of assessing movement in high risk infants. The application of this technology within pediatric practice represents a growing area of inter-disciplinary collaboration which may lead to a greater understanding of the development of the nervous system in infants at high risk of motor impairment.

  5. Miniature linear cooler development

    International Nuclear Information System (INIS)

    Pruitt, G.R.

    1993-01-01

    An overview is presented of the status of a family of miniature linear coolers currently under development by Hughes Aircraft Co. for use in hand held, volume limited or power limited infrared applications. These coolers, representing the latest additions to the Hughes family of TOP trademark [twin-opposed piston] linear coolers, have been fabricated and tested in three different configurations. Each configuration is designed to utilize a common compressor assembly resulting in reduced manufacturing costs. The baseline compressor has been integrated with two different expander configurations and has been operated with two different levels of input power. These various configuration combinations offer a wide range of performance and interface characteristics which may be tailored to applications requiring limited power and size without significantly compromising cooler capacity or cooldown characteristics. Key cooler characteristics and test data are summarized for three combinations of cooler configurations which are representative of the versatility of this linear cooler design. Configurations reviewed include the shortened coldfinger [1.50 to 1.75 inches long], limited input power [less than 17 Watts] for low power availability applications; the shortened coldfinger with higher input power for lightweight, higher performance applications; and coldfingers compatible with DoD 0.4 Watt Common Module coolers for wider range retrofit capability. Typical weight of these miniature linear coolers is less than 500 grams for the compressor, expander and interconnecting transfer line. Cooling capacity at 80K at room ambient conditions ranges from 400 mW to greater than 550 mW. Steady state power requirements for maintaining a heat load of 150 mW at 80K has been shown to be less than 8 Watts. Ongoing reliability growth testing is summarized including a review of the latest test article results

  6. Biometry and clinical characteristics of congenital cataracts and microphthalmia in the Miniature Schnauzer.

    Science.gov (United States)

    Gelatt, K N; Samuelson, D A; Barrie, K P; Das, N D; Wolf, E D; Bauer, J E; Andresen, T L

    1983-07-01

    Forty-two Miniature Schnauzer pups and adults with congenital cataracts and microphthalmia were evaluated by serial ophthalmic examinations, slit lamp biomicroscopic photography, and A-scan ultrasonography. The cataracts were evident when the eyelids opened at 2 weeks, affecting predominantly the lens nucleus and posterior cortex. Lenticonus was evident in 19% of the cataractous lenses. Progression of the cataracts was variable and related to involvement of the equatorial and posterior cortices. Lens-induced uveitis developed in some adult dogs with advanced hypermature cataracts. The globe and lens were smaller than normal in the cataractous eyes, as ascertained by A-scan ultrasonography. Age-matched comparisons of clear lens carrier Miniature Schnauzers and normal Beagles with the cataractous Miniature Schnauzers indicated affected globes and cataractous lenses were reduced 10% to 20% in their anteroposterior lengths. The microphthalmia appeared related to the congenital microphakic cataract.

  7. Miniaturization of components and systems for space using MEMS-technology

    Science.gov (United States)

    Grönland, Tor-Arne; Rangsten, Pelle; Nese, Martin; Lang, Martin

    2007-06-01

    Development of MEMS-based (micro electro mechanical system) components and subsystems for space applications has been pursued by various research groups and organizations around the world for at least two decades. The main driver for developing MEMS-based components for space is the miniaturization that can be achieved. Miniaturization can not only save orders of magnitude in mass and volume of individual components, but it can also allow increased redundancy, and enable novel spacecraft designs and mission scenarios. However, the commercial breakthrough of MEMS has not occurred within the space business as it has within other branches such as the IT/telecom or automotive industries, or as it has in biotech or life science applications. A main explanation to this is the highly conservative attitude to new technology within the space community. This conservatism is in many senses motivated by a very low risk acceptance in the few and costly space projects that actually ends with a space flight. To overcome this threshold there is a strong need for flight opportunities where reasonable risks can be accepted. Currently there are a few flight opportunities allowing extensive use of new technology in space, but one of the exceptions is the PRISMA program. PRISMA is an international (Sweden, Germany, France, Denmark, Norway, Greece) technology demonstration program with focus on rendezvous and formation flying. It is a two satellite LEO mission with a launch scheduled for the first half of 2009. On PRISMA, a number of novel technologies e.g. RF metrology sensor for Darwin, autonomous formation flying based on GPS and vision-based sensors, ADN-based "green propulsion" will be demonstrated in space for the first time. One of the satellites will also have a miniaturized propulsion system onboard based on MEMS-technology. This novel propulsion system includes two microthruster modules, each including four thrusters with micro- to milli-Newton thrust capability. The novelty

  8. Miniature shock tube for laser driven shocks.

    Science.gov (United States)

    Busquet, Michel; Barroso, Patrice; Melse, Thierry; Bauduin, Daniel

    2010-02-01

    We describe in this paper the design of a miniature shock tube (smaller than 1 cm(3)) that can be placed in a vacuum vessel and allows transverse optical probing and longitudinal backside extreme ultraviolet emission spectroscopy in the 100-500 A range. Typical application is the study of laser launched radiative shocks, in the framework of what is called "laboratory astrophysics."

  9. A Miniaturized Optical Sensor with Integrated Gas Cell

    NARCIS (Netherlands)

    Ayerden, N.P.; Ghaderi, M.; De Graaf, G.; Wolffenbuttel, R.F.

    2015-01-01

    The design, fabrication and characterization of a highly integrated optical gas sensor is presented. The gas cell takes up most of the space in a microspectrometer and is the only component that has so far not been miniaturized. Using the tapered resonator cavity of a linear variable optical filter

  10. Recombinant drugs-on-a-chip: The usage of capillary electrophoresis and trends in miniaturized systems – A review

    Energy Technology Data Exchange (ETDEWEB)

    Morbioli, Giorgio Gianini; Mazzu-Nascimento, Thiago; Aquino, Adriano [Instituto de Química de São Carlos, Universidade de São Paulo, Av. Trabalhador São-carlense, 400, 13566-590 São Carlos, SP (Brazil); Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas, SP (Brazil); Cervantes, Cesar [Instituto de Química de São Carlos, Universidade de São Paulo, Av. Trabalhador São-carlense, 400, 13566-590 São Carlos, SP (Brazil); Carrilho, Emanuel, E-mail: emanuel@iqsc.usp.br [Instituto de Química de São Carlos, Universidade de São Paulo, Av. Trabalhador São-carlense, 400, 13566-590 São Carlos, SP (Brazil); Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas, SP (Brazil)

    2016-09-07

    We present here a critical review covering conventional analytical tools of recombinant drug analysis and discuss their evolution towards miniaturized systems foreseeing a possible unique recombinant drug-on-a-chip device. Recombinant protein drugs and/or pro-drug analysis require sensitive and reproducible analytical techniques for quality control to ensure safety and efficacy of drugs according to regulatory agencies. The versatility of miniaturized systems combined with their low-cost could become a major trend in recombinant drugs and bioprocess analysis. Miniaturized systems are capable of performing conventional analytical and proteomic tasks, allowing for interfaces with other powerful techniques, such as mass spectrometry. Microdevices can be applied during the different stages of recombinant drug processing, such as gene isolation, DNA amplification, cell culture, protein expression, protein separation, and analysis. In addition, organs-on-chips have appeared as a viable alternative to testing biodrug pharmacokinetics and pharmacodynamics, demonstrating the capabilities of the miniaturized systems. The integration of individual established microfluidic operations and analytical tools in a single device is a challenge to be overcome to achieve a unique recombinant drug-on-a-chip device. - Highlights: • Principal analytical tools for analysis of recombinant drugs are presented. • A critical comparison among different substrates for fabrication of miniaturized systems is made. • Applications of miniaturized systems to produce recombinant drugs are shown. • Future trends of miniaturized systems capable of integrating analytical and proteomic tools in a single device are envisioned.

  11. Recombinant drugs-on-a-chip: The usage of capillary electrophoresis and trends in miniaturized systems – A review

    International Nuclear Information System (INIS)

    Morbioli, Giorgio Gianini; Mazzu-Nascimento, Thiago; Aquino, Adriano; Cervantes, Cesar; Carrilho, Emanuel

    2016-01-01

    We present here a critical review covering conventional analytical tools of recombinant drug analysis and discuss their evolution towards miniaturized systems foreseeing a possible unique recombinant drug-on-a-chip device. Recombinant protein drugs and/or pro-drug analysis require sensitive and reproducible analytical techniques for quality control to ensure safety and efficacy of drugs according to regulatory agencies. The versatility of miniaturized systems combined with their low-cost could become a major trend in recombinant drugs and bioprocess analysis. Miniaturized systems are capable of performing conventional analytical and proteomic tasks, allowing for interfaces with other powerful techniques, such as mass spectrometry. Microdevices can be applied during the different stages of recombinant drug processing, such as gene isolation, DNA amplification, cell culture, protein expression, protein separation, and analysis. In addition, organs-on-chips have appeared as a viable alternative to testing biodrug pharmacokinetics and pharmacodynamics, demonstrating the capabilities of the miniaturized systems. The integration of individual established microfluidic operations and analytical tools in a single device is a challenge to be overcome to achieve a unique recombinant drug-on-a-chip device. - Highlights: • Principal analytical tools for analysis of recombinant drugs are presented. • A critical comparison among different substrates for fabrication of miniaturized systems is made. • Applications of miniaturized systems to produce recombinant drugs are shown. • Future trends of miniaturized systems capable of integrating analytical and proteomic tools in a single device are envisioned.

  12. A miniature turbocompressor system

    Energy Technology Data Exchange (ETDEWEB)

    Zwyssig, C.; Kraehenbuehl, D.; Kolar, J. W. [Swiss Federal Institute of Technology, Power Electronic Systems Laboratory, Zuerich (Switzerland); Weser, H. [High Speed Turbomaschinen GmbH, Wolfsburg (Germany)

    2008-07-01

    The trend in compressors for fuel cells, heat pumps, aerospace and automotive air pressurization, heating, ventilation and air conditioning systems, is towards ultra-compact size and high efficiency. This can be achieved by increasing the rotational speed and employing new electrical drive system technology and materials. This paper presents a miniature, electrically driven turbocompressor system running at a speed of 500,000 rpm. The design includes the thermodynamics, the electric motor, the inverter, the control and the system integration with rotor dynamics and thermal considerations. In the experimental setup, the specified pressure ratio of 1.6 is achieved at a speed of 550,000 rpm, which is slightly higher than the design speed. (author)

  13. Miniature horizontal axis wind turbine system for multipurpose application

    International Nuclear Information System (INIS)

    Xu, F.J.; Yuan, F.G.; Hu, J.Z.; Qiu, Y.P.

    2014-01-01

    A MWT (miniature wind turbine) has received great attention recently for powering WISP (Wireless Intelligent Sensor Platform). In this study, two MHAWTs (miniature horizontal axis wind turbines) with and without gear transmission were designed and fabricated. A physics-based model was proposed and the optimal load resistances of the MHAWTs were predicted. The open circuit voltages, output powers and net efficiencies were measured under various ambient winds and load resistances. The experimental results showed the optimal load resistances matched well with the predicted results; the MHAWT without gear obtained higher output power at the wind speed of 2 m/s to 6 m/s, while the geared MHAWT exhibited better performance at the wind speed higher than 6 m/s. In addition, a DCM (discontinuous conduction mode) buck-boost converter was adopted as an interface circuit to maximize the charging power from MHAWTs to rechargeable batteries, exhibiting maximum efficiencies above 85%. The charging power reached about 8 mW and 36 mW at the wind speeds of 4 m/s and 6 m/s respectively, which indicated that the MHAWTs were capable for sufficient energy harvesting for powering low-power electronics continuously. - Highlights: • Performance of the miniature wind turbines with and without gears was compared. • The physics-based model was established and proved successfully. • The interface circuit with efficiency of more than 85% was designed

  14. Whole-genome sequencing reveals a potential causal mutation for dwarfism in the Miniature Shetland pony.

    Science.gov (United States)

    Metzger, Julia; Gast, Alana Christina; Schrimpf, Rahel; Rau, Janina; Eikelberg, Deborah; Beineke, Andreas; Hellige, Maren; Distl, Ottmar

    2017-04-01

    The Miniature Shetland pony represents a horse breed with an extremely small body size. Clinical examination of a dwarf Miniature Shetland pony revealed a lowered size at the withers, malformed skull and brachygnathia superior. Computed tomography (CT) showed a shortened maxilla and a cleft of the hard and soft palate which protruded into the nasal passage leading to breathing difficulties. Pathological examination confirmed these findings but did not reveal histopathological signs of premature ossification in limbs or cranial sutures. Whole-genome sequencing of this dwarf Miniature Shetland pony and comparative sequence analysis using 26 reference equids from NCBI Sequence Read Archive revealed three probably damaging missense variants which could be exclusively found in the affected foal. Validation of these three missense mutations in 159 control horses from different horse breeds and five donkeys revealed only the aggrecan (ACAN)-associated g.94370258G>C variant as homozygous wild-type in all control samples. The dwarf Miniature Shetland pony had the homozygous mutant genotype C/C of the ACAN:g.94370258G>C variant and the normal parents were heterozygous G/C. An unaffected full sib and 3/5 unaffected half-sibs were heterozygous G/C for the ACAN:g.94370258G>C variant. In summary, we could demonstrate a dwarf phenotype in a miniature pony breed perfectly associated with a missense mutation within the ACAN gene.

  15. Decrement of GABAA receptor-mediated inhibitory postsynaptic currents in dentate granule cells in epileptic hippocampus.

    Science.gov (United States)

    Isokawa, M

    1996-05-01

    1. Inhibitory postsynaptic currents (IPSCs) were studied in hippocampal dentate granule cells (DGCs) in the pilocarpine model and human temporal lobe epilepsy, with the use of the whole cell patch-clamp recording technique in slice preparations. 2. In the pilocarpine model, hippocampal slices were prepared from rats that were allowed to experience spontaneous seizures for 2 mo. Human hippocampal specimens were obtained from epileptic patients who underwent surgical treatment for medically intractable seizures. 3. IPSCs were generated by single perforant path stimulation and recorded at a membrane potential (Vm) of 0 mV near the reversal potential of glutamate excitatory postsynaptic currents in the voltage-clamp recording. IPSCs were pharmacologically identified as gamma-aminobutyric acid-A (GABAA) IPSCs by 10 microM bicuculline methiodide. 4. During low-frequency stimulation, IPSCs were not different in amplitude among non-seizure-experienced rat hippocampi, human nonsclerotic hippocampi, seizure-experienced rat hippocampi, and human sclerotic hippocampi. In the last two groups of DGCs, current-clamp recordings indicated the presence of prolonged excitatory postsynaptic potentials (EPSPs) mediated by the N-methyl-D-aspartate (NMDA) receptor. 5. High-frequency stimulation, administered at Vm = -30 mV to activate NMDA currents, reduced GABAA IPSC amplitude specifically in seizure-experienced rat hippocampi (t = 2.5, P < 0.03) and human sclerotic hippocampi (t = 7.7, P < 0.01). This reduction was blocked by an NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (APV) (50 microM). The time for GABAA IPSCs to recover to their original amplitude was also shortened by the application of APV. 6. I conclude that, when intensively activated, NMDA receptor-mediated excitatory transmission may interact with GABAergic synaptic inhibition in DGCs in seizure-experienced hippocampus to transiently reduce GABA(A) receptor-channel function. Such interactions may contribute to

  16. Two miniature electronic dosemeters Yperwatch - Gamcard

    International Nuclear Information System (INIS)

    Clavel, B.; Jaillon, J.

    1993-01-01

    Yperwatch and Gamcard were miniature electronic gamma personal dose and dose rate monitors. The Yperwatch is mounted in a wristwatch and the Gamcard in a case of the size of a standard credit card. The technology provides users with all the performance of a standard professional electronic dosemeter (integrated dose, dose rate, audible alarms, time in use). Yperwatch and Gamcard are based on well-proven electronic dosimetry technology, but with a greater ease of use. (author)

  17. A miniature Hopkinson experiment device based on multistage reluctance coil electromagnetic launch

    Science.gov (United States)

    Huang, Wenkai; Huan, Shi; Xiao, Ying

    2017-09-01

    A set of seven-stage reluctance miniaturized Hopkinson bar electromagnetic launcher has been developed in this paper. With the characteristics of high precision, small size, and little noise pollution, the device complies with the requirements of miniaturized Hopkinson bar for high strain rate. The launcher is a seven-stage accelerating device up to 65.5 m/s. A high performance microcontroller is used to control accurately the discharge of capacitor sets, by means of which the outlet velocity of the projectile can be controlled within a certain velocity range.

  18. A miniature Hopkinson experiment device based on multistage reluctance coil electromagnetic launch.

    Science.gov (United States)

    Huang, Wenkai; Huan, Shi; Xiao, Ying

    2017-09-01

    A set of seven-stage reluctance miniaturized Hopkinson bar electromagnetic launcher has been developed in this paper. With the characteristics of high precision, small size, and little noise pollution, the device complies with the requirements of miniaturized Hopkinson bar for high strain rate. The launcher is a seven-stage accelerating device up to 65.5 m/s. A high performance microcontroller is used to control accurately the discharge of capacitor sets, by means of which the outlet velocity of the projectile can be controlled within a certain velocity range.

  19. Immobilization of trypsin on miniature incandescent bulbs for infrared-assisted proteolysis

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Huimin; Bao, Huimin; Zhang, Luyan; Chen, Gang, E-mail: gangchen@fudan.edu.cn

    2014-10-03

    Highlights: • Trypsin was immobilized on miniature incandescent bulbs via chitosan coating. • The bulbs acted as enzymatic reactors and the generators of infrared radiation. • The bulb bioreactors were successfully employed in infrared-assisted proteolysis. • The proteolysis could accomplish within 5 min with high sequence coverages. - Abstract: A novel efficient proteolysis approach was developed based on trypsin-immobilized miniature incandescent bulbs and infrared (IR) radiation. Trypsin was covalently immobilized in the chitosan coating on the outer surface of miniature incandescent bulbs with the aid of glutaraldehyde. When an illuminated enzyme-immobilized bulb was immersed in protein solution, the emitted IR radiation could trigger and accelerate heterogeneous protein digestion. The feasibility and performance of the novel proteolysis approach were demonstrated by the digestion of hemoglobin (HEM), cytochrome c (Cyt-c), lysozyme (LYS), and ovalbumin (OVA) and the digestion time was significantly reduced to 5 min. The obtained digests were identified by MALDI-TOF-MS with the sequence coverages of 91%, 77%, 80%, and 52% for HEM, Cyt-c, LYS, and OVA (200 ng μL{sup −1} each), respectively. The suitability of the prepared bulb bioreactors to complex proteins was demonstrated by digesting human serum.

  20. Spontaneous intracranial hypotension.

    LENUS (Irish Health Repository)

    Fullam, L

    2012-01-31

    INTRODUCTION: Spontaneous\\/primary intracranial hypotension is characterised by orthostatic headache and is associated with characteristic magnetic resonance imaging findings. CASE REPORT: We present a case report of a patient with typical symptoms and classical radiological images. DISCUSSION: Spontaneous intracranial hypotension is an under-recognised cause of headache and can be diagnosed by history of typical orthostatic headache and findings on MRI brain.

  1. [Spontaneous bacterial peritonitis].

    Science.gov (United States)

    Velkey, Bálint; Vitális, Eszter; Vitális, Zsuzsanna

    2017-01-01

    Spontaneous bacterial peritonitis occurs most commonly in cirrhotic patients with ascites. Pathogens get into the circulation by intestinal translocation and colonize in peritoneal fluid. Diagnosis of spontaneous bacterial peritonitis is based on elevated polymorphonuclear leukocyte count in the ascites (>0,25 G/L). Ascites culture is often negative but aids to get information about antibiotic sensitivity in positive cases. Treatment in stable patient can be intravenous then orally administrated ciprofloxacin or amoxicillin/clavulanic acid, while in severe cases intravenous III. generation cephalosporin. Nosocomial spontaneous bacterial peritonitis often caused by Gram-positive bacteria and multi-resistant pathogens can also be expected thus carbapenem should be the choice of the empiric treatment. Antibiotic prophylaxis should be considered. Norfloxacin is used most commonly, but changes are expected due to increase in quinolone resistance. As a primary prophylaxis, a short-term antibiotic treatment is recommended after gastrointestinal bleeding for 5 days, while long-term prophylaxis is for patients with low ascites protein, and advanced disease (400 mg/day). Secondary prophylaxis is recommended for all patients recovered from spontaneous bacterial peritonitis. Due to increasing antibiotic use of antibiotics prophylaxis is debated to some degree. Orv. Hetil., 2017, 158(2), 50-57.

  2. Hodoscope module with miniature photomultipliers

    International Nuclear Information System (INIS)

    Bel'zer, L.I.; Gribushin, A.M.; Zhil'tsov, L.Ya.; Matveeva, E.N.; Philipenko, T.D.; Sinev, N.B.

    1987-01-01

    The experimental Scintillation Magnetic Spectrometer (SMS) installation, whose main element is an extended hodoscope system, is being built for the accelerator of the High Energy Laboratory of the Joint Institute for Nuclear Research. The authors describe the scintillation hodoscope of the SMS installation and present the applicable amplitude and time characteristics of several types of miniature photomultipliers (FEU-58, FEU-60, FEU-114-1, FEU-147-1, and R-1635 (Hamamatsu, Japan)), which were obtained with a 106 Ru radioactive source and standard plastic scintillators of two types, based on oxazoles in polystyrene and in polymethylmethacrylate

  3. Maintenance energy requirements in miniature colony dogs.

    Science.gov (United States)

    Serisier, S; Weber, M; Feugier, A; Fardet, M-O; Garnier, F; Biourge, V; German, A J

    2013-05-01

    There are numerous reports of maintenance energy requirements (MER) in dogs, but little information is available about energy requirements of miniature dog breeds. In this prospective, observational, cohort study, we aimed to determine MER in dogs from a number of miniature breeds and to determine which factors were associated with it. Forty-two dogs participated in the study. MER was calculated by determining daily energy intake (EI) during a period of 196 days (28-359 days) when body weight did not change significantly (e.g. ±2% in 12 weeks). Estimated median MER was 473 kJ/kg(0.75) /day (285-766 kJ/kg(0.75) /day), that is, median 113 kcal/kg(0.75) /day (68-183 kcal/kg(0.75) /day). In the obese dogs that lost weight, median MER after weight loss was completed was 360 kJ/kg(0.75) /day (285-515 kJ/kg(0.75) /day), that is, 86 kcal/kg(0.75) /day, (68-123 kcal/kg(0.75) /day). Simple linear regression analysis suggested that three breeds (e.g. Chihuahua, p = 0.002; Yorkshire terrier, p = 0.039; dachshund, p = 0.035) had an effect on MER. In addition to breed, simple linear regression revealed that neuter status (p = 0.079) and having previously been overweight (p = 0.002) were also of significance. However, with multiple linear regression analysis, only previous overweight status (MER less in dogs previously overweight p = 0.008) and breed (MER greater in Yorkshire terriers [p = 0.029] and less in Chihuahuas [p = 0.089]) remained in the final model. This study is the first to estimate MER in dogs of miniature breeds. Although further information from pet dogs is now needed, the current work will be useful for setting energy and nutrient requirement in such dogs for the future. Journal of Animal Physiology and Animal Nutrition © 2013 Blackwell Verlag GmbH.

  4. Miniature surgical robots in the era of NOTES and LESS: dream or reality?

    Science.gov (United States)

    Zygomalas, Apollon; Kehagias, Ioannis; Giokas, Konstantinos; Koutsouris, Dimitrios

    2015-02-01

    Laparoscopy is an established method for the treatment of numerous surgical conditions. Natural orifice transluminal endoscopic surgery (NOTES) is a novel surgical technique that uses the natural orifices of the human body as entrances to the abdominal cavity. An alternative concept of minimally invasive approach to the abdominal cavity is to insert all the laparoscopic instruments through ports using a single small incision on the abdominal wall. A suggested name for this technique is laparoendoscopic single-site surgery (LESS). Considering the technical difficulties in NOTES and LESS and the progress in informatics and robotics, the use of robots seems ideal. The aim of this study is to investigate if there is at present, a realistic possibility of using miniature robots in NOTES or LESS in daily clinical practice. An up-to-date review on in vivo surgical miniature robots is made. A Web-based research of the English literature up to March 2013 using PubMed, Scopus, and Google Scholar as search engines was performed. The development of in vivo miniature robots for use in NOTES or LESS is a reality with great advancements, potential advantages, and possible application in minimally invasive surgery in the future. However, true totally NOTES or LESS procedures on humans using miniature robots either solely or as assistance, remain a dream at present. © The Author(s) 2014.

  5. Canine disorder mirrors human disease: exonic deletion in HES7 causes autosomal recessive spondylocostal dysostosis in miniature Schnauzer dogs.

    Directory of Open Access Journals (Sweden)

    Cali E Willet

    Full Text Available Spondylocostal dysostosis is a congenital disorder of the axial skeleton documented in human families from diverse racial backgrounds. The condition is characterised by truncal shortening, extensive hemivertebrae and rib anomalies including malalignment, fusion and reduction in number. Mutations in the Notch signalling pathway genes DLL3, MESP2, LFNG, HES7 and TBX6 have been associated with this defect. In this study, spondylocostal dysostosis in an outbred family of miniature schnauzer dogs is described. Computed tomography demonstrated that the condition mirrors the skeletal defects observed in human cases, but unlike most human cases, the affected dogs were stillborn or died shortly after birth. Through gene mapping and whole genome sequencing, we identified a single-base deletion in the coding region of HES7. The frameshift mutation causes loss of functional domains essential for the oscillatory transcriptional autorepression of HES7 during somitogenesis. A restriction fragment length polymorphism test was applied within the immediate family and supported a highly penetrant autosomal recessive mode of inheritance. The mutation was not observed in wider testing of 117 randomly sampled adult miniature schnauzer and six adult standard schnauzer dogs; providing a significance of association of Praw = 4.759e-36 (genome-wide significant. Despite this apparently low frequency in the Australian population, the allele may be globally distributed based on its presence in two unrelated sires from geographically distant locations. While isolated hemivertebrae have been observed in a small number of other dog breeds, this is the first clinical and genetic diagnosis of spontaneously occurring spondylocostal dysostosis in a non-human mammal and offers an excellent model in which to study this devastating human disorder. The genetic test can be utilized by dog breeders to select away from the disease and avoid unnecessary neonatal losses.

  6. Canine disorder mirrors human disease: exonic deletion in HES7 causes autosomal recessive spondylocostal dysostosis in miniature Schnauzer dogs.

    Science.gov (United States)

    Willet, Cali E; Makara, Mariano; Reppas, George; Tsoukalas, George; Malik, Richard; Haase, Bianca; Wade, Claire M

    2015-01-01

    Spondylocostal dysostosis is a congenital disorder of the axial skeleton documented in human families from diverse racial backgrounds. The condition is characterised by truncal shortening, extensive hemivertebrae and rib anomalies including malalignment, fusion and reduction in number. Mutations in the Notch signalling pathway genes DLL3, MESP2, LFNG, HES7 and TBX6 have been associated with this defect. In this study, spondylocostal dysostosis in an outbred family of miniature schnauzer dogs is described. Computed tomography demonstrated that the condition mirrors the skeletal defects observed in human cases, but unlike most human cases, the affected dogs were stillborn or died shortly after birth. Through gene mapping and whole genome sequencing, we identified a single-base deletion in the coding region of HES7. The frameshift mutation causes loss of functional domains essential for the oscillatory transcriptional autorepression of HES7 during somitogenesis. A restriction fragment length polymorphism test was applied within the immediate family and supported a highly penetrant autosomal recessive mode of inheritance. The mutation was not observed in wider testing of 117 randomly sampled adult miniature schnauzer and six adult standard schnauzer dogs; providing a significance of association of Praw = 4.759e-36 (genome-wide significant). Despite this apparently low frequency in the Australian population, the allele may be globally distributed based on its presence in two unrelated sires from geographically distant locations. While isolated hemivertebrae have been observed in a small number of other dog breeds, this is the first clinical and genetic diagnosis of spontaneously occurring spondylocostal dysostosis in a non-human mammal and offers an excellent model in which to study this devastating human disorder. The genetic test can be utilized by dog breeders to select away from the disease and avoid unnecessary neonatal losses.

  7. Generation of miniaturized planar ecombinant antibody arrays using a microcantilever-based printer

    Science.gov (United States)

    Petersson, Linn; Berthet Duroure, Nathalie; Auger, Angèle; Dexlin-Mellby, Linda; Borrebaeck, Carl AK; Ait Ikhlef, Ali; Wingren, Christer

    2014-07-01

    Miniaturized (Ø 10 μm), multiplexed (>5-plex), and high-density (>100 000 spots cm-2) antibody arrays will play a key role in generating protein expression profiles in health and disease. However, producing such antibody arrays is challenging, and it is the type and range of available spotters which set the stage. This pilot study explored the use of a novel microspotting tool, BioplumeTM—consisting of an array of micromachined silicon cantilevers with integrated microfluidic channels—to produce miniaturized, multiplexed, and high-density planar recombinant antibody arrays for protein expression profiling which targets crude, directly labelled serum. The results demonstrated that 16-plex recombinant antibody arrays could be produced—based on miniaturized spot features (78.5 um2, Ø 10 μm) at a 7-125-times increased spot density (250 000 spots cm-2), interfaced with a fluorescent-based read-out. This prototype platform was found to display adequate reproducibility (spot-to-spot) and an assay sensitivity in the pM range. The feasibility of the array platform for serum protein profiling was outlined.

  8. Generation of miniaturized planar ecombinant antibody arrays using a microcantilever-based printer

    International Nuclear Information System (INIS)

    Petersson, Linn; Dexlin-Mellby, Linda; Borrebaeck, Carl AK; Wingren, Christer; Berthet Duroure, Nathalie; Auger, Angèle; Ait Ikhlef, Ali

    2014-01-01

    Miniaturized (Ø 10 μm), multiplexed (>5-plex), and high-density (>100 000 spots cm −2 ) antibody arrays will play a key role in generating protein expression profiles in health and disease. However, producing such antibody arrays is challenging, and it is the type and range of available spotters which set the stage. This pilot study explored the use of a novel microspotting tool, Bioplume TM —consisting of an array of micromachined silicon cantilevers with integrated microfluidic channels—to produce miniaturized, multiplexed, and high-density planar recombinant antibody arrays for protein expression profiling which targets crude, directly labelled serum. The results demonstrated that 16-plex recombinant antibody arrays could be produced—based on miniaturized spot features (78.5 um 2 , Ø 10 μm) at a 7–125-times increased spot density (250 000 spots cm −2 ), interfaced with a fluorescent-based read-out. This prototype platform was found to display adequate reproducibility (spot-to-spot) and an assay sensitivity in the pM range. The feasibility of the array platform for serum protein profiling was outlined. (paper)

  9. Genetics Home Reference: primary spontaneous pneumothorax

    Science.gov (United States)

    ... Home Health Conditions Primary spontaneous pneumothorax Primary spontaneous pneumothorax Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Primary spontaneous pneumothorax is an abnormal accumulation of air in the ...

  10. AMINA-chip : a miniaturized measurement system for ambient ammonia

    NARCIS (Netherlands)

    Timmer, Björn Herman

    2004-01-01

    The development of a miniaturized and integrated measurement system for gaseous ammonia is described in this thesis. The measuring principle, ¿AMINA¿, is an indirect method for selectively measuring ammonia that makes use of pH-transitions, electrolyte conductivity detection and phaseseparating

  11. Testing the impact of miniaturization on phylogeny: Paleozoic dissorophoid amphibians.

    Science.gov (United States)

    Fröbisch, Nadia B; Schoch, Rainer R

    2009-06-01

    Among the diverse clade of Paleozoic dissorophoid amphibians, the small, terrestrial amphibamids and the neotenic branchiosaurids have frequently been suggested as possible antecedents of either all or some of the modern amphibian clades. Classically, amphibamids and branchiosaurids have been considered to represent distinct, but closely related clades within dissorophoids, but despite their importance for the controversial lissamphibian origins, a comprehensive phylogenetic analysis of small dissorophoids has thus far not been attempted. On the basis of an integrated data set, the relationships of amphibamids and branchiosaurids were analyzed using parsimony and Bayesian approaches. Both groups represent miniaturized forms and it was tested whether similar developmental pathways, associated with miniaturization, lead to an artificial close relationship of branchiosaurids and amphibamids. Moreover, the fit of the resulting tree topologies to the distribution of fossil taxa in the stratigraphic rock record was assessed as an additional source of information. The results show that characters associated with a miniaturized morphology are not responsible for the close clustering of branchiosaurids and amphibamids. Instead, all analyses invariably demonstrate a monophyletic clade of branchiosaurids highly nested within derived amphibamids, indicating that branchiosaurids represent a group of secondarily neotenic amphibamid dissorophoids. This understanding of the phylogenetic relationships of small dissorophoid amphibians provides a new framework for the discussion of their evolutionary history and the evolution of characters shared by branchiosaurids and/or amphibamids with modern amphibian taxa.

  12. Synaptic Homeostasis and Allostasis in the Dentate Gyrus Caused by Inflammatory and Neuropathic Pain Conditions

    Directory of Open Access Journals (Sweden)

    Rui-Rui Wang

    2018-01-01

    Full Text Available It has been generally accepted that pain can cause imbalance between excitation and inhibition (homeostasis at the synaptic level. However, it remains poorly understood how this imbalance (allostasis develops in the CNS under different pain conditions. Here, we analyzed the changes in both excitatory and inhibitory synaptic transmission and modulation of the dentate gyrus (DG under two pain conditions with different etiology and duration. First, it was revealed that the functions of the input-output (I/O curves for evoked excitatory postsynaptic currents (eEPSCs following the perforant path (PP stimulation were gained under both acute inflammatory and chronic neuropathic pain conditions relative to the controls. However, the functions of I/O curves for the PP-evoked inhibitory postsynaptic currents (eIPSCs differed between the two conditions, namely it was greatly gained under inflammatory condition, but was reduced under neuropathic condition in reverse. Second, both the frequency and amplitude of miniature IPSCs (mIPSCs were increased under inflammatory condition, however a decrease in frequency of mIPSCs was observed under neuropathic condition. Finally, the spike discharge of the DG granule cells in response to current injection was significantly increased by neuropathic pain condition, however, no different change was found between inflammatory pain condition and the control. These results provide another line of evidence showing homeostatic and allostatic modulation of excitatory synaptic transmission by inhibitory controls under different pathological pain conditions, hence implicating use of different therapeutic approaches to maintain the homeostasis between excitation and inhibition while treating different conditions of pathological pain.

  13. Potential of Gene Editing and Induced Pluripotent Stem Cells (iPSCs) in Treatment of Retinal Diseases.

    Science.gov (United States)

    Chuang, Katherine; Fields, Mark A; Del Priore, Lucian V

    2017-12-01

    The advent of gene editing has introduced the ability to make changes to the genome of cells, thus allowing for correction of genetic mutations in patients with monogenic diseases. Retinal diseases are particularly suitable for the application of this new technology because many retinal diseases, such as Stargardt disease, retinitis pigmentosa (RP), and Leber congenital amaurosis (LCA), are monogenic. Moreover, gene delivery techniques such as the use of adeno-associated virus (AAV) vectors have been optimized for intraocular use, and phase III trials are well underway to treat LCA, a severe form of inherited retinal degeneration, with gene therapy. This review focuses on the use of gene editing techniques and another relatively recent advent, induced pluripotent stem cells (iPSCs), and their potential for the study and treatment of retinal disease. Investment in these technologies, including overcoming challenges such as off-target mutations and low transplanted cell integration, may allow for future treatment of many debilitating inherited retinal diseases.

  14. Analysis of serum and cerebrospinal fluid in clinically normal adult miniature donkeys.

    Science.gov (United States)

    Mozaffari, A A; Samadieh, H

    2013-09-01

    To establish reference intervals for serum and cerebrospinal fluid (CSF) parameters in clinically healthy adult miniature donkeys. Experiments were conducted on 10 female and 10 male clinically normal adult miniature donkeys, randomly selected from five herds. Lumbosacral CSF collection was performed with the sedated donkey in the standing position. Cell analysis was performed immediately after the samples were collected. Blood samples were obtained from the jugular vein immediately after CSF sample collection. Sodium, potassium, glucose, urea nitrogen, total protein, calcium, chloride, phosphorous and magnesium concentrations were measured in CSF and serum samples. A paired t-test was used to compare mean values between female and male donkeys. The CSF was uniformly clear, colourless and free from flocculent material, with a specific gravity of 1.002. The range of total nucleated cell counts was 2-4 cells/μL. The differential white cell count comprised only small lymphocytes. No erythrocytes or polymorphonuclear cells were observed on cytological examination. Reference values were obtained for biochemical analysis of serum and CSF. Gender had no effect on any variables measured in serum or CSF (p>0.05). CSF analysis can provide important information in addition to that gained by clinical examination. CSF analysis has not previously been performed in miniature donkeys; this is the first report on the subject. In the present study, reference intervals for total nucleated cell count, total protein, glucose, urea nitrogen, sodium, potassium, chloride, calcium, phosphorous and magnesium concentrations of serum and CSF were determined for male and female miniature donkeys.

  15. Design of a miniaturized integrated spectrometer for spectral tissue sensing

    Science.gov (United States)

    Belay, Gebirie Yizengaw; Hoving, Willem; Ottevaere, Heidi; van der Put, Arthur; Weltjens, Wim; Thienpont, Hugo

    2016-04-01

    Minimally-invasive image-guided procedures become increasingly used by physicians to obtain real-time characterization feedback from the tissue at the tip of their interventional device (needle, catheter, endoscopic or laparoscopic probes, etc…) which can significantly improve the outcome of diagnosis and treatment, and ultimately reduce cost of the medical treatment. Spectral tissue sensing using compact photonic probes has the potential to be a valuable tool for screening and diagnostic purposes, e.g. for discriminating between healthy and tumorous tissue. However, this technique requires a low-cost broadband miniature spectrometer so that it is commercially viable for screening at point-of-care locations such as physicians' offices and outpatient centers. Our goal is therefore to develop a miniaturized spectrometer based on diffractive optics that combines the functionalities of a visible/near-infrared (VIS/NIR) and shortwave-infrared (SWIR) spectrometer in one very compact housing. A second goal is that the hardware can be produced in high volume at low cost without expensive time consuming alignment and calibration steps. We have designed a miniaturized spectrometer which operates both in the visible/near-infrared and shortwave-infrared wavelength regions ranging from 400 nm to 1700 nm. The visible/near-infrared part of the spectrometer is designed for wavelengths from 400 nm to 800 nm whereas the shortwave-infrared segment ranges from 850 nm to 1700 nm. The spectrometer has a resolution of 6 nm in the visible/near-infrared wavelength region and 10 nm in the shortwave-infrared. The minimum SNR of the spectrometer for the intended application is about 151 in the VIS/NIR range and 6000 for SWIR. In this paper, the modelling and design, and power budget analysis of the miniaturized spectrometer are presented. Our work opens a door for future affordable micro- spectrometers which can be integrated with smartphones and tablets, and used for point

  16. Miniature photometric stereo system for textile surface structure reconstruction

    Science.gov (United States)

    Gorpas, Dimitris; Kampouris, Christos; Malassiotis, Sotiris

    2013-04-01

    In this work a miniature photometric stereo system is presented, targeting the three-dimensional structural reconstruction of various fabric types. This is a supportive module to a robot system, attempting to solve the well known "laundry problem". The miniature device has been designed for mounting onto the robot gripper. It is composed of a low-cost off-the-shelf camera, operating in macro mode, and eight light emitting diodes. The synchronization between image acquisition and lighting direction is controlled by an Arduino Nano board and software triggering. The ambient light has been addressed by a cylindrical enclosure. The direction of illumination is recovered by locating the reflection or the brightest point on a mirror sphere, while a flatfielding process compensates for the non-uniform illumination. For the evaluation of this prototype, the classical photometric stereo methodology has been used. The preliminary results on a large number of textiles are very promising for the successful integration of the miniature module to the robot system. The required interaction with the robot is implemented through the estimation of the Brenner's focus measure. This metric successfully assesses the focus quality with reduced time requirements in comparison to other well accepted focus metrics. Besides the targeting application, the small size of the developed system makes it a very promising candidate for applications with space restrictions, like the quality control in industrial production lines or object recognition based on structural information and in applications where easiness in operation and light-weight are required, like those in the Biomedical field, and especially in dermatology.

  17. Progress and bottleneck in induced pluripotency

    Directory of Open Access Journals (Sweden)

    Zhang Zhen-Ning

    2012-07-01

    Full Text Available Abstract With their capability to undergo unlimited self-renewal and to differentiate into all cell types in the body, induced pluripotent stem cells (iPSCs, reprogrammed from somatic cells of individual patients with defined factors, have unlimited potential in cell therapy and in modeling complex human diseases. Significant progress has been achieved to improve the safety of iPSCs and the reprogramming efficiency. To avoid the cancer risk and spontaneous reactivation of the reprogramming factors associated with the random integration of viral vectors into the genome, several approaches have been established to deliver the reprogramming factors into the somatic cells without inducing genetic modification. In addition, a panel of small molecule compounds, many of which targeting the epigenetic machinery, have been identified to increase the reprogramming efficiency. Despite these progresses, recent studies have identified genetic and epigenetic abnormalities of iPSCs as well as the immunogenicity of some cells derived from iPSCs. In addition, due to the oncogenic potential of the reprogramming factors and the reprogramming-induced DNA damage, the critical tumor suppressor pathways such as p53 and ARF are activated to act as the checkpoints that suppress induced pluripotency. The inactivation of these tumor suppression pathways even transiently during reprogramming processes could have significant adverse impact on the genome integrity. These safety concerns must be resolved to improve the feasibility of the clinic development of iPSCs into human cell therapy.

  18. The mass miniature chest radiography programme in Cape Town ...

    African Journals Online (AJOL)

    Background. Tuberculosis (TB) control programmes rely mainly on passive detection of symptomatic individuals. The resurgence of TB has rekindled interest in active case finding. Cape Town (South Africa) had a mass miniature radiography (MMR) screening programme from 1948 to 1994. Objective. To evaluate screening ...

  19. Disposable Miniaturized Screen‐Printed pH and Reference Electrodes for Potentiometric Systems

    DEFF Research Database (Denmark)

    Musa, Arnaud Emmanuel; del Campo, Francisco Javier; Abramova, Natalia

    2011-01-01

    This work describes the development of a miniaturized potentiometric system comprising a miniaturized quasi‐reference electrode (QRE) coupled to a solid‐state ion‐selective electrode (ISE) for the monitoring of pH. We describe the optimization of materials and fabrication processes including screen‐printing...... electrode) that can be used continuously for a period of not less than 7 days in aqueous solutions. Curing the Ag/AgCl pastes during 20 minutes at 120 °C after printing allowed the QREs to display excellent potential stability, as demonstrated by an open‐circuit‐potential standard deviation of ±1.2 mV over...

  20. Ziprasidone-induced spontaneous orgasm.

    Science.gov (United States)

    Boora, K; Chiappone, K; Dubovsky, S; Xu, J

    2010-06-01

    Neuroleptic treatment in schizophrenic patients has been associated with sexual dysfunction, including impotence and decreased libido. Spontaneous ejaculation without sexual arousal during typical antipsychotic treatment is a rare condition that has been described with zuclopentixol, trifluoperazine, and thiothixene. Here, we are reporting a case of spontaneous orgasm with ziprasidone in a bipolar patient. This patient began to repeatedly experience spontaneous sexual arousal and orgasm, which she had never experienced in the past. Ziprasidone might be causing an increase in sexual orgasm by 5-HT2 receptor antagonism, which preclinical evidence suggests that it facilitates dopamine release in the cortex.

  1. Adeno-associated virus transformation into the normal miniature pig and the normal guinea pigs cochlea via scala tympani.

    Science.gov (United States)

    Shi, Xunbei; Wu, Nan; Zhang, Yue; Guo, Weiwei; Lin, Chang; Yang, Shiming

    2017-09-01

    To investigate the expression of the miniature pig cochlea after AAV1 transfect into the cochlea via round window membrane (RWM). Twenty miniature pigs are equally divided into four experimental groups. Twelve miniature pigs are equally divided into four control groups. Each pig was transfected with the AAV1 in the experimental group via RWM and each pig was transduced with the artificial perilymph in the control group. The expression of green fluorescent protein (GFP) was observed at 2 weeks, 3 weeks and 4 weeks, respectively. Likewise, AAV1 was delivered into the guinea pigs cochleas using the same method, and the results were compared with that of the miniature pigs. The expression was mainly in the inner hair cells of the miniature pig. The expression of GFP began to appear at 2 weeks, reached the peak at 3 weeks. It also expressed in Hensen's cells, inner pillar cells, outer pillar cells, spiral limbus, and spiral ligament. In the meanwhile, AAV1 was delivered into guinea pig cochlea via the same method, and AAV1 was also expressed in the inner hair cells. But the expression peaked at 2 weeks, and the efficiency of the inner hair cell transfection was higher than that of the pig. AAV1 can be transformed into miniature pig cochlea via scala tympani by the RWM method efficiently.

  2. Development of a miniature autofluorescence device for the early diagnosis of squamous cell carcinoma

    Science.gov (United States)

    Patil, Ajeetkumar; Rao K., Swati; V. K., Unnikrishnan; Pai, Keerthilatha M.; Kartha, V. B.; Chidangil, Santhosh

    2017-07-01

    Autofluorescence spectroscopy offer noninvasive and promising tools for the detection of alternations biochemical compositions of tissues and cells, in presence of disease. They have the added advantage of being highly objective due to the fact that diagnostic evaluation is by statistical methods, eliminating errors from lack of experience, fatigue factor, and subjectivity of visual perceptions. The present research work involves in designing and assembling of a low cost, miniature oral cancer screening device with for routine clinical applications. A miniature system was designed and assembled with much smaller and cost-effective components like compact light source and miniature spectrometer, in a hand-held unit configuration. The performance of the system was evaluated using animal -mouse- SCC model. The current system can be used in handheld operation, which makes it very useful for many applications like, screening of squamous cell carcinoma susceptible population.

  3. The effects of electrospun substrate-mediated cell colony morphology on the self-renewal of human induced pluripotent stem cells.

    Science.gov (United States)

    Maldonado, Maricela; Wong, Lauren Y; Echeverria, Cristina; Ico, Gerardo; Low, Karen; Fujimoto, Taylor; Johnson, Jed K; Nam, Jin

    2015-05-01

    The development of xeno-free, chemically defined stem cell culture systems has been a primary focus in the field of regenerative medicine to enhance the clinical application of pluripotent stem cells (PSCs). In this regard, various electrospun substrates with diverse physiochemical properties were synthesized utilizing various polymer precursors and surface treatments. Human induced pluripotent stem cells (IPSCs) cultured on these substrates were characterized by their gene and protein expression to determine the effects of the substrate physiochemical properties on the cells' self-renewal, i.e., proliferation and the maintenance of pluripotency. The results showed that surface chemistry significantly affected cell colony formation via governing the colony edge propagation. More importantly, when surface chemistry of the substrates was uniformly controlled by collagen conjugation, the stiffness of substrate was inversely related to the sphericity, a degree of three dimensionality in colony morphology. The differences in sphericity subsequently affected spontaneous differentiation of IPSCs during a long-term culture, implicating that the colony morphology is a deciding factor in the lineage commitment of PSCs. Overall, we show that the capability of controlling IPSC colony morphology by electrospun substrates provides a means to modulate IPSC self-renewal. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Miniature sources of irradiation for intracavitary thermo radiotherapy

    Science.gov (United States)

    Taubin, M.; Chesnokov, D.; Simonov, A.

    2018-02-01

    This report presents the development of a miniature ionizing and thermal radiation source for oncological diseases treatment namely the inward parts of the body. This source can be placed next to the tumor inside of the body. This report is only about methods and devices for the intracavitary therapy. Irradiation by external sources wasn’t considered in our investigation.

  5. Miniaturized Spacecraft Platform for Command, Data Handling and Electronics, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Microelectronics Research Development Corporation (Micro RDC) proposes to develop a platform of low mass/volume/power, reliable miniaturized electronic modules that...

  6. Long Life Miniature Hall Thruster Enabling Low Cost Human Precursor Missions

    Data.gov (United States)

    National Aeronautics and Space Administration — Key and Central Objectives: This investigation aims to demonstrate that the application of magnetic shielding technology on miniature Hall thrusters will...

  7. Miniature Heat Pipes

    Science.gov (United States)

    1997-01-01

    Small Business Innovation Research contracts from Goddard Space Flight Center to Thermacore Inc. have fostered the company work on devices tagged "heat pipes" for space application. To control the extreme temperature ranges in space, heat pipes are important to spacecraft. The problem was to maintain an 8-watt central processing unit (CPU) at less than 90 C in a notebook computer using no power, with very little space available and without using forced convection. Thermacore's answer was in the design of a powder metal wick that transfers CPU heat from a tightly confined spot to an area near available air flow. The heat pipe technology permits a notebook computer to be operated in any position without loss of performance. Miniature heat pipe technology has successfully been applied, such as in Pentium Processor notebook computers. The company expects its heat pipes to accommodate desktop computers as well. Cellular phones, camcorders, and other hand-held electronics are forsible applications for heat pipes.

  8. Miniature ionization chamber

    International Nuclear Information System (INIS)

    Alexeev, V.I.; Emelyanov, I.Y.; Ivanov, V.M.; Konstantinov, L.V.; Lysikov, B.V.; Postnikov, V.V.; Rybakov, J.V.

    1976-01-01

    A miniature ionization chamber having a gas-filled housing which accommodates a guard electrode made in the form of a hollow perforated cylinder is described. The cylinder is electrically associated with the intermediate coaxial conductor of a triaxial cable used as the lead-in of the ionization chamber. The gas-filled housing of the ionization chamber also accommodates a collecting electrode shaped as a rod electrically connected to the center conductor of the cable and to tubular members. The rod is disposed internally of the guard electrode and is electrically connected, by means of jumpers passing through the holes in the guard electrode, to the tubular members. The tubular members embrace the guard electrode and are spaced a certain distance apart along its entire length. Arranged intermediate of these tubular members are spacers secured to the guard electrode and fixing the collecting electrode throughout its length with respect to the housing of the ionization chamber

  9. Ultrathin Graphene-Protein Supercapacitors for Miniaturized Bioelectronics.

    Science.gov (United States)

    Mosa, Islam M; Pattammattel, Ajith; Kadimisetty, Karteek; Pande, Paritosh; El-Kady, Maher F; Bishop, Gregory W; Novak, Marc; Kaner, Richard B; Basu, Ashis K; Kumar, Challa V; Rusling, James F

    2017-09-06

    Nearly all implantable bioelectronics are powered by bulky batteries which limit device miniaturization and lifespan. Moreover, batteries contain toxic materials and electrolytes that can be dangerous if leakage occurs. Herein, an approach to fabricate implantable protein-based bioelectrochemical capacitors (bECs) employing new nanocomposite heterostructures in which 2D reduced graphene oxide sheets are interlayered with chemically modified mammalian proteins, while utilizing biological fluids as electrolytes is described. This protein-modified reduced graphene oxide nanocomposite material shows no toxicity to mouse embryo fibroblasts and COS-7 cell cultures at a high concentration of 1600 μg mL -1 which is 160 times higher than those used in bECs, unlike the unmodified graphene oxide which caused toxic cell damage even at low doses of 10 μg mL -1 . The bEC devices are 1 μm thick, fully flexible, and have high energy density comparable to that of lithium thin film batteries. COS-7 cell culture is not affected by long-term exposure to encapsulated bECs over 4 d of continuous charge/discharge cycles. These bECs are unique, protein-based devices, use serum as electrolyte, and have the potential to power a new generation of long-life, miniaturized implantable devices.

  10. Miniature Non-Intrusive Multi-Parameter Oronasal Respiratory Health Monitor, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Redondo Optics Inc. (ROI), proposes to develop, demonstrate, and deliver to NASA an intrinsically safe, miniature, low power, autonomous, and self-calibrated,...

  11. Challenges in miniaturized automotive long-range lidar system design

    Science.gov (United States)

    Fersch, Thomas; Weigel, Robert; Koelpin, Alexander

    2017-05-01

    This paper discusses the current technical limitations posed on endeavors to miniaturize lidar systems for use in automotive applications and how to possibly extend those limits. The focus is set on long-range scanning direct time of flight LiDAR systems using APD photodetectors. Miniaturization evokes severe problems in ensuring absolute laser safety while maintaining the systems' performance in terms of maximum range, signal-to-noise ratio, detection probability, pixel density, or frame rate. Based on hypothetical but realistic specifications for an exemplary system the complete lidar signal path is calculated. The maximum range of the system is used as a general performance indicator. It is determined with the minimum signal-to-noise ratio required to detect an object. Various system parameters are varied to find their impact on the system's range. The reduction of the laser's pulse width and the right choice for the transimpedance amplifier's amplification have shown to be practicable measures to double the system's range.

  12. Assessing the use of Low Voltage UV-light Emitting Miniature LEDs for Marine Biofouling Control

    Science.gov (United States)

    2016-07-01

    of that required to drive traditional UV mercury lamps . Secondly, given their small size and relatively low cost, UV LEDs provide ease of maintenance...UNCLASSIFIED UNCLASSIFIED Assessing the use of Low Voltage UV -light Emitting Miniature LEDs for Marine Biofouling Control Richard...settling organisms. The introduction of miniature UV light emitting diodes ( LEDs ) as a light source enables them to be embedded into thin, flexible

  13. Miniaturized Ultrasound Imaging Probes Enabled by CMUT Arrays with Integrated Frontend Electronic Circuits

    Science.gov (United States)

    Khuri-Yakub, B. (Pierre) T.; Oralkan, Ömer; Nikoozadeh, Amin; Wygant, Ira O.; Zhuang, Steve; Gencel, Mustafa; Choe, Jung Woo; Stephens, Douglas N.; de la Rama, Alan; Chen, Peter; Lin, Feng; Dentinger, Aaron; Wildes, Douglas; Thomenius, Kai; Shivkumar, Kalyanam; Mahajan, Aman; Seo, Chi Hyung; O’Donnell, Matthew; Truong, Uyen; Sahn, David J.

    2010-01-01

    Capacitive micromachined ultrasonic transducer (CMUT) arrays are conveniently integrated with frontend integrated circuits either monolithically or in a hybrid multichip form. This integration helps with reducing the number of active data processing channels for 2D arrays. This approach also preserves the signal integrity for arrays with small elements. Therefore CMUT arrays integrated with electronic circuits are most suitable to implement miniaturized probes required for many intravascular, intracardiac, and endoscopic applications. This paper presents examples of miniaturized CMUT probes utilizing 1D, 2D, and ring arrays with integrated electronics. PMID:21097106

  14. Miniature fuel cells relieve gas pressure in sealed batteries

    Science.gov (United States)

    Frank, H. A.

    1971-01-01

    Miniature fuel cells within sealed silver zinc batteries consume evolved hydrogen and oxygen rapidly, preventing pressure rupturing. They do not significantly increase battery weight and they operate in all battery life phases. Complete gas pressure control requires two fuel cells during all phases of operation of silver zinc batteries.

  15. Small scale monitoring of a bioremediation barrier using miniature electrical resistivity tomography

    Science.gov (United States)

    Sentenac, Philippe; Hogson, Tom; Keenan, Helen; Kulessa, Bernd

    2015-04-01

    The aim of this study was to assess, in the laboratory, the efficiency of a barrier of oxygen release compound (ORC) to block and divert a diesel plume migration in a scaled aquifer model using miniature electrical resistivity tomography (ERT) as the monitoring system. Two plumes of contaminant (diesel) were injected in a soil model made of local sand and clay. The diesel plumes migration was imaged and monitored using a miniature resistivity array system that has proved to be accurate in soil resistivity variations in small-scaled models of soil. ERT results reflected the lateral spreading and diversion of the diesel plumes in the unsaturated zone. One of the contaminant plumes was partially blocked by the ORC barrier and a diversion and reorganisation of the diesel in the soil matrix was observed. The technique of time-lapse ERT imaging showed that a dense non-aqueous phase liquid (DNAPL) contaminant like diesel can be monitored through a bioremediation barrier and the technique is well suited to monitor the efficiency of the barrier. Therefore, miniature ERT as a small-scale modelling tool could complement conventional techniques, which require more expensive and intrusive site investigation prior to remediation.

  16. The concept and application of miniaturization boiling in cooling system

    International Nuclear Information System (INIS)

    Suhaimi Illias; Muhammad Asri Idris

    2009-01-01

    The purpose of this research is to study and examine the phenomena of miniaturization-boiling, which intensely scatters with a large number of minute liquid particles from a water droplet surface to the atmosphere, when the droplet collided with a heating surface. As the material of the heating surface, the following were used: stainless steel (SUS 303 A Cr=17%,Ni=8%), sapphire (Al 3 O 2 ), brass, copper and carbon plane. The material was heated in order to study the miniaturization-boiling and droplet bounding phenomena at a very high temperature (160 degree C- 420 degree C). The phenomenon was photographed by a high-speed camera (10,000 fps) from the horizontal direction. The nuclear fusion reactor needs a very severe cooling, heat removal cooling method by special boiling is lead to this research. (Author)

  17. A Miniature Probe for Ultrasonic Penetration of a Single Cell

    Directory of Open Access Journals (Sweden)

    Mingfei Xiao

    2009-05-01

    Full Text Available Although ultrasound cavitation must be avoided for safe diagnostic applications, the ability of ultrasound to disrupt cell membranes has taken on increasing significance as a method to facilitate drug and gene delivery. A new ultrasonic resonance driving method is introduced to penetrate rigid wall plant cells or oocytes with springy cell membranes. When a reasonable design is created, ultrasound can gather energy and increase the amplitude factor. Ultrasonic penetration enables exogenous materials to enter cells without damaging them by utilizing instant acceleration. This paper seeks to develop a miniature ultrasonic probe experiment system for cell penetration. A miniature ultrasonic probe is designed and optimized using the Precise Four Terminal Network Method and Finite Element Method (FEM and an ultrasonic generator to drive the probe is designed. The system was able to successfully puncture a single fish cell.

  18. Development of a micromirror-scanned multimodal CARS miniaturized microscope for the in vivo study of spinal cord disorders

    Science.gov (United States)

    Murugkar, Sangeeta; Smith, Brett; Naji, Majid; Brideau, Craig; Stys, Peter; Anis, Hanan

    2011-03-01

    We discuss the design and implementation of a novel multimodal coherent anti-Stokes Raman scattering (CARS) miniaturized microscope for imaging of injured and recovering spinal cords in a single living animal. We demonstrate for the first time, the use of a biaxial microelectromechanical system (MEMS) mirror for scanning and diffraction limited multiple lens miniaturized objective for exciting a CARS signal. The miniaturized microscope design includes light delivery using a large mode area photonic crystal fiber (PCF), and multimode fiber for collection of the nonlinear optical signal. The basic design concept, major engineering challenges, solutions, and preliminary results are presented. We demonstrate CARS and two photon excitation fluorescence microscopy in a benchtop setup with the miniaturized optics and MEMS scanning. The light source is based on a single femtosecond laser (pump beam) and a supercontinuum generated in a nonlinear PCF (Stokes beam). This is coupled using free space optics onto the surface of a resonantly driven two dimensional scanning MEMS mirror that scans the excitation light in a Lissajous pattern. The novel design of the miniaturized microscope is expected to provide significant new information on the pathogenesis of demyelinating diseases such as Multiple Sclerosis and Spinal Cord Injury.

  19. Kidney-differentiated cells derived from Lowe Syndrome patient's iPSCs show ciliogenesis defects and Six2 retention at the Golgi complex.

    Directory of Open Access Journals (Sweden)

    Wen-Chieh Hsieh

    Full Text Available Lowe syndrome is an X-linked condition characterized by congenital cataracts, neurological abnormalities and kidney malfunction. This lethal disease is caused by mutations in the OCRL1 gene, which encodes for the phosphatidylinositol 5-phosphatase Ocrl1. While in the past decade we witnessed substantial progress in the identification and characterization of LS patient cellular phenotypes, many of these studies have been performed in knocked-down cell lines or patient's cells from accessible cell types such as skin fibroblasts, and not from the organs affected. This is partially due to the limited accessibility of patient cells from eyes, brain and kidneys. Here we report the preparation of induced pluripotent stem cells (iPSCs from patient skin fibroblasts and their reprogramming into kidney cells. These reprogrammed kidney cells displayed primary cilia assembly defects similar to those described previously in cell lines. Additionally, the transcription factor and cap mesenchyme marker Six2 was substantially retained in the Golgi complex and the functional nuclear-localized fraction was reduced. These results were confirmed using different batches of differentiated cells from different iPSC colonies and by the use of the human proximal tubule kidney cell line HK2. Indeed, OCRL1 KO led to both ciliogenesis defects and Six2 retention in the Golgi complex. In agreement with Six2's role in the suppression of ductal kidney lineages, cells from this pedigree were over-represented among patient kidney-reprogrammed cells. We speculate that this diminished efficacy to produce cap mesenchyme cells would cause LS patients to have difficulties in replenishing senescent or damaged cells derived from this lineage, particularly proximal tubule cells, leading to pathological scenarios such as tubular atrophy.

  20. Disposable Fluidic Actuators for Miniature In-Vivo Surgical Robotics.

    Science.gov (United States)

    Pourghodrat, Abolfazl; Nelson, Carl A

    2017-03-01

    Fusion of robotics and minimally invasive surgery (MIS) has created new opportunities to develop diagnostic and therapeutic tools. Surgical robotics is advancing from externally actuated systems to miniature in-vivo robotics. However, with miniaturization of electric-motor-driven surgical robots, there comes a trade-off between the size of the robot and its capability. Slow actuation, low load capacity, sterilization difficulties, leaking electricity and transferring produced heat to tissues, and high cost are among the key limitations of the use of electric motors in in-vivo applications. Fluid power in the form of hydraulics or pneumatics has a long history in driving many industrial devices and could be exploited to circumvent these limitations. High power density and good compatibility with the in-vivo environment are the key advantages of fluid power over electric motors when it comes to in-vivo applications. However, fabrication of hydraulic/pneumatic actuators within the desired size and pressure range required for in-vivo surgical robotic applications poses new challenges. Sealing these types of miniature actuators at operating pressures requires obtaining very fine surface finishes which is difficult and costly. The research described here presents design, fabrication, and testing of a hydraulic/pneumatic double-acting cylinder, a limited-motion vane motor, and a balloon-actuated laparoscopic grasper. These actuators are small, seal-less, easy to fabricate, disposable, and inexpensive, thus ideal for single-use in-vivo applications. To demonstrate the ability of these actuators to drive robotic joints, they were modified and integrated in a robotic arm. The design and testing of this surgical robotic arm are presented to validate the concept of fluid-power actuators for in-vivo applications.

  1. Circuits and Systems for Low-Power Miniaturized Wireless Sensors

    Science.gov (United States)

    Nagaraju, Manohar

    The field of electronic sensors has witnessed a tremendous growth over the last decade particularly with the proliferation of mobile devices. New applications in Internet of Things (IoT), wearable technology, are further expected to fuel the demand for sensors from current numbers in the range of billions to trillions in the next decade. The main challenges for a trillion sensors are continued miniaturization, low-cost and large-scale manufacturing process, and low power consumption. Traditional integration and circuit design techniques in sensor systems are not suitable for applications in smart dust, IoT etc. The first part of this thesis demonstrates an example sensor system for biosignal recording and illustrates the tradeoffs in the design of low-power miniaturized sensors. The different components of the sensor system are integrated at the board level. The second part of the thesis demonstrates fully integrated sensors that enable extreme miniaturization of a sensing system with the sensor element, processing circuitry, a frequency reference for communication and the communication circuitry in a single hermetically sealed die. Design techniques to reduce the power consumption of the sensor interface circuitry at the architecture and circuit level are demonstrated. The principles are used to design sensors for two of the most common physical variables, mass and pressure. A low-power wireless mass and pressure sensor suitable for a wide variety of biological/chemical sensing applications and Tire Pressure Monitoring Systems (TPMS) respectively are demonstrated. Further, the idea of using high-Q resonators for a Voltage Controlled Oscillator (VCO) is proposed and a low-noise, wide bandwidth FBAR-based VCO is presented.

  2. A Miniaturize Bandpass Filter with Harmonic Suppression Using Meandered Quarter-Wavelength Resonators

    Directory of Open Access Journals (Sweden)

    Yun-Long Lu

    2014-01-01

    Full Text Available A miniaturized bandpass filter with harmonics suppression is presented. The proposed filter consists of two quarter-wavelength microstrip resonators, which are meandered for circuit size reduction. An interdigital capacitor, loading at zero-voltage point, is employed to provide the desired coupling between the resonators at operating frequency, whereas the coupling coefficient at the third harmonic is realized to be zero. Besides, the second and fourth harmonics are suppressed since λ/4 resonators are adopted. Benefiting from these properties, a miniaturized bandpass filter with the second, third, and fourth harmonics suppression was designed and implemented. The final measured and simulated results show good consistence with the theoretical counterparts.

  3. Miniature probe with semiconductor photodiode for measuring dose rates in radiotherapy

    International Nuclear Information System (INIS)

    Burian, A.

    1991-01-01

    The probe is designed for gaining information on the magnitude and spatial distribution of the dose which will be absorbed by the patient's body during radiotherapy. The probe satisfies requirements of high-level miniaturization and requirements on the shape and tissue-equivalence of the casing, as well as on efficient electromagnetic shielding. It is fitted with a miniature photodiode. Conductive carbon cement was used for attaching contacts to the photodiode. Efficient electromagnetic shielding was achieved by means of a carbon-based conductive layer. The photodiode casing was made from a mixture of organic materials whose biogenic elements approximate the standard soft human tissue. The geometry of the casing is adapted to the particular field of application of the probe. (Z.S). 2 figs

  4. Miniature GC: Minicell ion mobility spectrometer (IMS) for astrobiology planetary missions

    Science.gov (United States)

    Kojiro, Daniel R.; Holland, Paul M.; Stimac, Robert M.; Kaye, William J.; Takeuchi, Norishige

    2006-01-01

    Astrobiology flight experiments require highly sensitive instrumentation for in situ analysis of volatile chemical species and minerals present in the atmospheres and surfaces of planets, moons, and asteroids. The complex mixtures encountered place a heavy burden on the analytical instrumentation to detect and identify all species present. The use of land rovers and balloon aero-rovers place additional emphasis on miniaturization of the analytical instrumentation. In addition, smaller instruments, using tiny amounts of consumables, allow the use of more instrumentation and/or longer mission life for stationary landers/laboratories. We describe here the development of a miniature GC - Minicell Ion Mobility Spectrometer (IMS) under development through NASA's Astrobiology Science and Technology Instrument Development (ASTID) Program and NASA's Small Business Innovative Research (SBIR) Program.

  5. Spontaneous rib fractures.

    Science.gov (United States)

    Katrancioglu, Ozgur; Akkas, Yucel; Arslan, Sulhattin; Sahin, Ekber

    2015-07-01

    Other than trauma, rib fracture can occur spontaneously due to a severe cough or sneeze. In this study, patients with spontaneous rib fractures were analyzed according to age, sex, underlying pathology, treatment, and complications. Twelve patients who presented between February 2009 and February 2011 with spontaneous rib fracture were reviewed retrospectively. The patients' data were evaluated according to anamnesis, physical examination, and chest radiographs. The ages of the patients ranged from 34 to 77 years (mean 55.91 ± 12.20 years), and 7 (58.4%) were male. All patients had severe cough and chest pain. The fractures were most frequently between 4th and 9th ribs; multiple rib fractures were detected in 5 (41.7%) patients. Eight (66.7%) patients had chronic obstructive pulmonary disease, 2 (16.7%) had bronchial asthma, and 2 (16.7%) had osteoporosis. Bone densitometry revealed a high risk of bone fracture in all patients. Patients with chronic obstructive pulmonary disease or bronchial asthma had been treated with high-dose steroids for over a year. Spontaneous rib fracture due to severe cough may occur in patients with osteoporosis, chronic obstructive pulmonary disease, or bronchial asthma, receiving long-term steroid therapy. If these patients have severe chest pain, chest radiography should be performed to check for bone lesions. © The Author(s) 2015.

  6. Generation of induced pluripotent stem cells (iPSCs) from an Alzheimer's disease patient carrying an A79V mutation in PSEN1

    DEFF Research Database (Denmark)

    Li, Tong; Pires, Carlota; Nielsen, Troels Tolstrup

    2016-01-01

    Skin fibroblasts were obtained from a 48-year-old presymptomatic woman carrying a A79V mutation in the presenilin 1 gene (PSEN1), causing Alzheimer's disease (AD). Induced pluripotent stem cell (iPSCs) were derived via transfection with episomal vectors carrying hOCT4, hSOX2, hKLF2, hL-MYC, hLIN28...... and shTP53 genes. A79V-iPSCs were free of genomically integrated reprogramming genes, had the specific mutation but no additional genomic aberrancies, expressed the expected pluripotency markers and displayed in vitro differentiation potential to the three germ layers. The reported A79V-iPSCs line may...

  7. Generation of induced pluripotent stem cells (iPSCs) from an Alzheimer's disease patient carrying a M146I mutation in PSEN1

    DEFF Research Database (Denmark)

    Li, Tong; Pires, Carlota; Nielsen, Troels Tolstrup

    2016-01-01

    Skin fibroblasts were obtained from a 46-year-old symptomatic man carrying a M146I mutation in the presenilin 1 gene (PSEN1), responsible for causing Alzheimer's disease (AD). Induced pluripotent stem cells (iPSCs) were derived via transfection with episomal vectors carrying hOCT4, hSOX2, hKLF2, h......L-MYC, hLIN28 and shTP53 genes. M146I-iPSCs were free of genomically integrated reprogramming genes, had the specific mutation but no additional genomic aberrancies, expressed the expected pluripotency markers and displayed in vitro differentiation potential to the three germ layers. The reported M146I...

  8. Parallel spatial direct numerical simulations on the Intel iPSC/860 hypercube

    Science.gov (United States)

    Joslin, Ronald D.; Zubair, Mohammad

    1993-01-01

    The implementation and performance of a parallel spatial direct numerical simulation (PSDNS) approach on the Intel iPSC/860 hypercube is documented. The direct numerical simulation approach is used to compute spatially evolving disturbances associated with the laminar-to-turbulent transition in boundary-layer flows. The feasibility of using the PSDNS on the hypercube to perform transition studies is examined. The results indicate that the direct numerical simulation approach can effectively be parallelized on a distributed-memory parallel machine. By increasing the number of processors nearly ideal linear speedups are achieved with nonoptimized routines; slower than linear speedups are achieved with optimized (machine dependent library) routines. This slower than linear speedup results because the Fast Fourier Transform (FFT) routine dominates the computational cost and because the routine indicates less than ideal speedups. However with the machine-dependent routines the total computational cost decreases by a factor of 4 to 5 compared with standard FORTRAN routines. The computational cost increases linearly with spanwise wall-normal and streamwise grid refinements. The hypercube with 32 processors was estimated to require approximately twice the amount of Cray supercomputer single processor time to complete a comparable simulation; however it is estimated that a subgrid-scale model which reduces the required number of grid points and becomes a large-eddy simulation (PSLES) would reduce the computational cost and memory requirements by a factor of 10 over the PSDNS. This PSLES implementation would enable transition simulations on the hypercube at a reasonable computational cost.

  9. Loss of CDKL5 in Glutamatergic Neurons Disrupts Hippocampal Microcircuitry and Leads to Memory Impairment in Mice.

    Science.gov (United States)

    Tang, Sheng; Wang, I-Ting Judy; Yue, Cuiyong; Takano, Hajime; Terzic, Barbara; Pance, Katarina; Lee, Jun Y; Cui, Yue; Coulter, Douglas A; Zhou, Zhaolan

    2017-08-02

    Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a neurodevelopmental disorder characterized by epileptic seizures, severe intellectual disability, and autistic features. Mice lacking CDKL5 display multiple behavioral abnormalities reminiscent of the disorder, but the cellular origins of these phenotypes remain unclear. Here, we find that ablating CDKL5 expression specifically from forebrain glutamatergic neurons impairs hippocampal-dependent memory in male conditional knock-out mice. Hippocampal pyramidal neurons lacking CDKL5 show decreased dendritic complexity but a trend toward increased spine density. This morphological change is accompanied by an increase in the frequency of spontaneous miniature EPSCs and interestingly, miniature IPSCs. Using voltage-sensitive dye imaging to interrogate the evoked response of the CA1 microcircuit, we find that CA1 pyramidal neurons lacking CDKL5 show hyperexcitability in their dendritic domain that is constrained by elevated inhibition in a spatially and temporally distinct manner. These results suggest a novel role for CDKL5 in the regulation of synaptic function and uncover an intriguing microcircuit mechanism underlying impaired learning and memory. SIGNIFICANCE STATEMENT Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a severe neurodevelopmental disorder caused by mutations in the CDKL5 gene. Although Cdkl5 constitutive knock-out mice have recapitulated key aspects of human symptomatology, the cellular origins of CDKL5 deficiency-related phenotypes are unknown. Here, using conditional knock-out mice, we show that hippocampal-dependent learning and memory deficits in CDKL5 deficiency have origins in glutamatergic neurons of the forebrain and that loss of CDKL5 results in the enhancement of synaptic transmission and disruptions in neural circuit dynamics in a spatially and temporally specific manner. Our findings demonstrate that CDKL5 is an important regulator of synaptic function in glutamatergic neurons and

  10. Some characteristics of a miniature neutron spectrometer

    International Nuclear Information System (INIS)

    Sekimoto, H.; Oishi, K.; Hojo, K.; Hojo, T.

    1984-01-01

    Some characteristics of an NE213 miniature spherical spectrometer for in-assembly fast-neutron spectrometry were measured. As the bubbling time changed, the pulse-height did not change appreciably, but the n-γ discrimination characteristics changed considerably. As the count rate changed, the pulse-height did not change appreciably, and the change of the n-γ discrimination characteristics was acceptable. The neutron response function was measured to be almost isotropic except for the backward direction. (orig.)

  11. Vestibular-evoked myogenic potentials in miniature pigs

    Directory of Open Access Journals (Sweden)

    Xi Shi

    2016-06-01

    Conclusion: The latencies and thresholds of VEMPs recorded from the neck extensor muscle and the masseter muscle appear to be comparable in normal adult Bama miniature pigs, although the amplitude recorded from the neck extensor muscle seems to be higher than that from the masseter muscle. However, because of their usually relatively superficial and easily accessible location, as well as their large volume and strong contractions, masseter muscles may be better target muscles for recording myogenic potentials.

  12. Evaluation of computed tomographic and radiographic myelography in normal miniature pigs

    International Nuclear Information System (INIS)

    Choi, M.H.; Lee, H.Y.; Kim, M.E.; Kim, J.Y.; Lee, N.S.; Chang, J.H.; Jung, J.H.; Choi, M.C.

    2010-01-01

    Evaluation of the myelography was studied in miniature pigs. Radiographs and computed tomographic (CT) images of the whole spine were obtained at clinically healthy twelve miniature pigs of 4 (8.7-10 kg) and 12 (26-31 kg) months. The assessments of the spinal cord were made in accordance with the Pavlov's method and compared area ratio [at spinal cord (SC), vertebral canal (VC) and vertebral body (VB)]. The Pavlov's ratio in the cervical spine was significant larger than that of thoracolumbar in radiographic myelography. On CT myelography, the area of the spinal cord had a significant difference between the cervical and thoracolumbar spine. Among the cervical spine, the ratios of spinal cord and vertebral body (SC : VB), vertebral canal and vertebral body (VC : VB) were minimum at the level of 4th cervical spine in both ages, while maximum at the level of 6th cervical spine in both months. In case of lumbar spine, the ratios of spinal cord and vertebral body (SC : VB) were the largest at the level of 4th lumbar spine in 4 months and at the level of 3rd lumbar spine in 12 months. In addition, the ratio of spinal cord and vertebral body (SC : VB) of the cervical spinal cord was significant lower at 4 months but the lumbar spinal cord showed lower pattern at 12 months old miniature pigs

  13. A novel 2nd-order bandpass MFSS filter with miniaturized structure

    Directory of Open Access Journals (Sweden)

    C. Y. Fang

    2015-08-01

    Full Text Available In order to effectively obtain a miniaturized structure and good filtering properties, we propose a novel 2nd-order bandpass metamaterial frequency selective surface (MFSS filter which contains two capacitive layers and one inductive layer, where there are multi-loop metallic patches as shunt capacitor C and planar wire grids as series inductor L respectively. Unlike the traditional operation way—the tuned elements used in resonant surface approximately equal to one wavelength in circumference and the structure thickness with a spacing of a quarter wavelength apart, by changing the value of L and C and matching multilayer dielectric to adjust the LC coupling resonance and the resonance impedance respectively, the proposed MFSS filter can achieves a miniatured structure with ideal bandpass properties. Measurement results of the fabricated prototype of the bandpass filter (BPF indicate that the dimension of the tuned element on resonant surface is approximately 0.025 wavelength, i.e., 0.025λ. At the same time, the filter has the stable center frequency of f0 = 1.53GHz and the transmittance of T ⩾ 96.3% and high Q-value for the TE/TM wave polarization at various incidence angles. The novel 2nd-order bandpass MFSS filter with miniaturized structure not only can decrease structure dimension, but also has a wide range of applications to microwave and infrared band.

  14. Comparison of Miniaturized and Conventional Asymmetrical Flow Field-Flow Fractionation (AF4 Channels for Nanoparticle Separations

    Directory of Open Access Journals (Sweden)

    Zengchao You

    2017-03-01

    Full Text Available The performance of a miniaturized channel for the separation of polymer and metal nanoparticles (NP using Asymmetrical Flow Field-Flow Fractionation (AF4 was investigated and compared with a conventional AF4 system. To develop standard separation methods, experimental parameters like cross flow, gradient profile and injection time were varied and optimized. Corresponding chromatographic parameters were calculated and compared. Our results indicate that the chromatographic resolution in the miniaturized channel is lower, whereas significantly shorter analyses time and less solvent consumption were obtained. Moreover, the limit of detection (LOD and limit of quantification (LOQ obtained from hyphenation with a UV-detector are obviously lower than in a conventional channel, which makes the miniaturized channel interesting for trace analysis.

  15. Anatomy of adult Megaphragma (Hymenoptera: Trichogrammatidae, one of the smallest insects, and new insight into insect miniaturization.

    Directory of Open Access Journals (Sweden)

    Alexey A Polilov

    Full Text Available The body size, especially in cases of extreme reduction, is an important characteristic that strongly determines the morphology, physiology, and biology of animals. Miniaturization is a widespread trend in animal evolution and one of the principal directions of evolution in insects. Miniaturization-related features of insect morphology have been subject to intensive studies during the last few years, but the structure of the smallest insects remains insufficiently known. It is especially important to study hymenopterans of the genus Megaphragma, which include the smallest flying insects and a species in which an almost anucleate nervous system was recently discovered. This article is the first detailed study of the external and internal morphology of adults of Megaphragma mymaripenne and M. amalphitanum using histological methods, 3D computer modeling and other techniques. It is shown that in spite of the extremely small size the organization of Megaphragma retains a considerkable level of structural complexity. On the other hand, miniaturization leads to re-organizations of several organ systems. Unique structural features related to miniaturization have been found in both species: lysis of cell bodies and nuclei of neurons at late stages of pupal development, absence of the heart, and considerable reductions in the set of muscles. Comparative analysis of structure in the smallest insects representing different taxa has revealed common features of the evolutionary process of miniaturization in insects.

  16. A Fluorescence Based Miniaturized Detection Module for Toxin Producing Algae

    Science.gov (United States)

    Zieger, S. E.; Mistlberger, G.; Troi, L.; Lang, A.; Holly, C.; Klimant, I.

    2016-12-01

    Algal blooms are sensitive to external environmental conditions and may pose a serious threat to marine and human life having an adverse effect on the ecosystem. Harmful algal blooms can produce different toxins, which can lead to massive fish kills or to human disorders. Facing these problems, miniaturized and low-cost instrumentation for an early detection and identification of harmful algae classes has become more important over the last years. 1,2Based on the characteristic pigment pattern of different algae classes, we developed a miniaturized detection module, which is able to detect and identify algae classes after analyzing their spectral behavior. Our device combines features of a flow-cytometer and fluorimeter and is build up as a miniaturized and low-cost device of modular design. Similar to a fluorimeter, it excites cells in the capillary with up to 8 different excitation wavelengths recording the emitted fluorescence at 4 different emission channels. Furthermore, the device operates in a flow-through mode similar to a flow-cytometer, however, using only low-cost elements such as LEDs and photodiodes. Due to its miniaturized design, the sensitivity and selectivity increase, whereas background effects are reduced. With a sampling frequency of 140 Hz, we try to detect and count particular cell events even at a concentration of 2 cells / 7.3 µL illuminated volume. Using a self-learning multivariate algorithm, the data are evaluated autonomously on the device enabling an in-situ analysis. The flexibility in choosing excitation and emission wavelengths as well as the high sampling rate enables laboratory applications such as measuring induction kinetics. However, in its first application, the device is part of an open and modular monitoring system enabling the sensing of chemical compounds such as toxic and essential Hg, Cd, Pb, As and Cu trace metal species, nutrients and species related to the carbon cycle, VOCs and potentially toxic algae classes (FP7

  17. Does malaria epidemiology project Cameroon as `Africa in miniature'?

    Indian Academy of Sciences (India)

    Cameroon, a west-central African country with a ∼20 million population, is commonly regarded as 'Africa in miniature' due to the extensive biological and cultural diversities of whole Africa being present in a single-country setting. This country is inhabited by ancestral human lineages in unique eco-climatic conditions and ...

  18. Spontaneous tension haemopneumothorax.

    Science.gov (United States)

    Patterson, Benjamin Oliver; Itam, Sarah; Probst, Fey

    2008-10-31

    We present a patient with sudden onset progressive shortness of breath and no history of trauma, who rapidly became haemodynamically compromised with a pneumothorax and pleural effusion seen on chest radiograph. He was treated for spontaneous tension pneumothorax but this was soon revealed to be a tension haemopneumothorax. He underwent urgent thoracotomy after persistent bleeding to explore an apical vascular abnormality seen on CT scanning. To our knowledge this is the first such case reported.Aetiology and current approach to spontaneous haemothorax are discussed briefly.

  19. Inward rectifier K+ channel and T-type Ca2+ channel contribute to enhancement of GABAergic transmission induced by β1-adrenoceptor in the prefrontal cortex.

    Science.gov (United States)

    Luo, Fei; Zheng, Jian; Sun, Xuan; Tang, Hua

    2017-02-01

    The functions of prefrontal cortex (PFC) are sensitive to norepinephrine (NE). Endogenously released NE influences synaptic transmission through activation of different subtypes of adrenergic receptors in PFC including α 1 , α 2 , β 1 or β 2 -adrenoceptor. Our recent study has revealed that β 1 -adrenoceptor (β 1 -AR) activation modulates glutamatergic transmission in the PFC, whereas the roles of β 1 -AR in GABAergic transmission are elusive. In the current study, we probed the effects of the β 1 -AR agonist dobutamine (Dobu) on GABAergic transmission onto pyramidal neurons in the PFC of juvenile rats. Dobu increased both the frequency and amplitude of miniature IPSCs (mIPSCs). Ca 2+ influx through T-type voltage-gated Ca 2+ channel was required for Dobu-enhanced mIPSC frequency. We also found that Dobu facilitated GABA release probability and the number of releasable vesicles through regulating T-type Ca 2+ channel. Dobu depolarized GABAergic fast-spiking (FS) interneurons with no effects on the firing rate of action potentials (APs) of interneurons. Dobu-induced depolarization of FS interneurons required inward rectifier K + channel (Kir). Our results suggest that Dobu increase GABA release via inhibition of Kir, which further depolarizes FS interneurons resulting in Ca 2+ influx via T-type Ca 2+ channel. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. INSTRUMENTAL MINIATURES BY THE COMPOSER GHEORGHE NEAGA: BETWEEN THE OLD AND THE NEW

    Directory of Open Access Journals (Sweden)

    CHICIUC NATALIA

    2016-12-01

    Full Text Available The miniature occupies an important place in Gheorghe Neaga’s instrumental chamber repertoire. Th e number of his small creations is impressive, being found both in the teaching repertoire of artistic education institutions and in the artistsinstrumentalists’ concert repertoire. Dedicated to piano, violin and piano or other instruments, the pieces refl ect in a perfect measure the author’s artistic predilections, more or less infl uenced by the evolution of compositional techniques. On this line, the proposed objective in this article is to examine some unelucidated miniatures through the old-new binomial spectrum.

  1. A Molecular Diagnostic Test for Persistent Müllerian Duct Syndrome in Miniature Schnauzer Dogs

    OpenAIRE

    Pujar, S.; Meyers-Wallen, V.N.

    2009-01-01

    In persistent Müllerian duct syndrome (PMDS), Müllerian ducts fail to regress in males during sexual differentiation. In the canine miniature schnauzer model, PMDS is caused by a C to T transition in exon 3 of the Müllerian inhibiting substance type II receptor (MISRII), which introduces a DdeI restriction site. Here we report a molecular diagnostic test for PMDS in the miniature schnauzer to identify affected dogs and carriers. As our test results suggest that the mutation is identical by de...

  2. Electric field distribution and current emission in a miniaturized geometrical diode

    Science.gov (United States)

    Lin, Jinpu; Wong, Patrick Y.; Yang, Penglu; Lau, Y. Y.; Tang, W.; Zhang, Peng

    2017-06-01

    We study the electric field distribution and current emission in a miniaturized geometrical diode. Using Schwarz-Christoffel transformation, we calculate exactly the electric field inside a finite vacuum cathode-anode (A-K) gap with a single trapezoid protrusion on one of the electrode surfaces. It is found that there is a strong field enhancement on both electrodes near the protrusion, when the ratio of the A-K gap distance to the protrusion height d /h spot checked against COMSOL simulations. We calculate the effective field enhancement factor for the field emission current, by integrating the local Fowler-Nordheim current density along the electrode surfaces. We systematically examine the electric field enhancement and the current rectification of the miniaturized geometrical diode for various geometric dimensions and applied electric fields.

  3. Research and Development of Miniaturized Fuel Evaporation Closed Chamber for Motorcycle

    Directory of Open Access Journals (Sweden)

    Hong Bin

    2016-01-01

    Full Text Available With the increasingly serious environmental pollution, pollution emissions of motorcycles had gradually been concerned in all developed countries. But the fuel evaporative emissions had not attracted sufficient attention and its test equipment was far from perfect. Thus, this paper addressed the miniaturized problems of closed chamber. On the basis of analyzing fuel evaporative emission regulations and the features of closed room, technical solutions are determined and a prototype was successfully developed. The paper successfully resolved the seal problem and innovatively developed the pressure balance system and the temperature and humidity regulation system. After experimental verification, the prototype had reliable performance and stable operation. And it met the requirements of the relevant standards and it was also equivalent to imported equipments. Thus, this paper successfully resolved the miniaturized problems of closed chamber.

  4. Discovery of skin alkaloids in a miniaturized eleutherodactylid frog from Cuba.

    Science.gov (United States)

    Rodríguez, Ariel; Poth, Dennis; Schulz, Stefan; Vences, Miguel

    2011-06-23

    Four phylogenetically independent lineages of frogs are currently known to sequester lipid-soluble skin alkaloids for which a dietary source has been demonstrated. We report here a remarkable fifth such instance, in Eleutherodactylus iberia and Eleutherodactylus orientalis, two species of miniaturized frogs of the family Eleutherodactylidae from Cuba. Six pumiliotoxins and two indolizidines were found in E. iberia, one of the smallest frogs in the world and characterized by a contrasting colour pattern for which we hypothesize an aposematic function. Analyses of stomach content indicated a numerical prevalence of mites with an important proportion of oribatids-a group of arthropods known to contain one of the pumiliotoxins detected in E. iberia. This suggests that miniaturization and specialization to small prey may have favoured the acquisition of dietary skin alkaloids in these amphibians.

  5. Diagnosis of chronic active hepatitis in a miniature schnauzer.

    Science.gov (United States)

    Hendrix, Alana D

    2004-09-01

    A 12-year-old male castrated miniature schnauzer was presented with a history of abdominal distension. Serum biochemical analysis and abdominal ultrasonography indicated hepatic disease. A wedge biopsy provided a diagnosis of chronic active hepatitis. A therapeutic regime was initiated to improve the quality of life and slow the progression of this disease is described.

  6. Diagnosis of chronic active hepatitis in a miniature schnauzer

    OpenAIRE

    Hendrix, Alana D.

    2004-01-01

    A 12-year-old male castrated miniature schnauzer was presented with a history of abdominal distension. Serum biochemical analysis and abdominal ultrasonography indicated hepatic disease. A wedge biopsy provided a diagnosis of chronic active hepatitis. A therapeutic regime was initiated to improve the quality of life and slow the progression of this disease is described.

  7. Spontaneous tension haemopneumothorax

    Directory of Open Access Journals (Sweden)

    Itam Sarah

    2008-10-01

    Full Text Available Abstract We present a patient with sudden onset progressive shortness of breath and no history of trauma, who rapidly became haemodynamically compromised with a pneumothorax and pleural effusion seen on chest radiograph. He was treated for spontaneous tension pneumothorax but this was soon revealed to be a tension haemopneumothorax. He underwent urgent thoracotomy after persistent bleeding to explore an apical vascular abnormality seen on CT scanning. To our knowledge this is the first such case reported. Aetiology and current approach to spontaneous haemothorax are discussed briefly.

  8. Neuron-astrocyte interaction enhance GABAergic synaptic transmission in a manner dependent on key metabolic enzymes.

    Directory of Open Access Journals (Sweden)

    Przemysław eKaczor

    2015-04-01

    Full Text Available GABA is the major inhibitory neurotransmitter in the adult brain and mechanisms of GABAergic inhibition have been intensely investigated in the past decades. Recent studies provided evidence for an important role of astrocytes in shaping GABAergic currents. One of the most obvious, but yet poorly understood, mechanisms of the cross-talk between GABAergic currents and astrocytes is metabolism including neurotransmitter homeostasis. In particular, how modulation of GABAergic currents by astrocytes depends on key enzymes involved in cellular metabolism remains largely unknown. To address this issue, we have considered two simple models of neuronal cultures: nominally astrocyte-free neuronal culture (NC and neuronal-astrocytic co-cultures (ANCC and miniature Inhibitory Postsynaptic Currents (mIPSCs were recorded in control conditions and in the presence of respective enzyme blockers. We report that enrichment of neuronal culture with astrocytes results in a marked increase in mIPSC frequency. This enhancement of GABAergic activity was accompanied by increased number of GAD65 and vGAT puncta, indicating that at least a part of the frequency enhancement was due to increased number of synaptic contacts. Inhibition of glutamine synthetase (with MSO strongly reduced mIPSC frequency in ANCC but had no effect in NC. Moreover, treatment of ANCC with inhibitor of glycogen phosphorylase (BAYU6751 or with selective inhibitor of astrocytic Krebs cycle,fluoroacetate, resulted in a marked reduction of mIPSC frequency in ANCC having no effect in NC. We conclude that GABAergic synaptic transmission strongly depends on neuron-astrocyte interaction in a manner dependent on key metabolic enzymes as well as on the Krebs cycle.

  9. Fabrication of a miniature diamond grinding tool using a hybrid process of micro-EDM and co-deposition

    International Nuclear Information System (INIS)

    Chen, Shun-Tong; Lai, Yun-Cheng; Liu, Ching-Chang

    2008-01-01

    A novel miniature diamond grinding tool usable for the precise micro-grinding of miniature parts is presented. A hybrid process that combines 'micro-EDM' with 'precision co-deposition' is proposed. The metal substrate is micro-EDMed to a 50 µm diameter and micro diamonds with 0–2 µm grains are 'electroformed' on the substrate surface, producing a miniature multilayered grinding tool. Nickel and diamond act as binders and cutters, respectively. A partition plate with an array of drilled holes is designed to ensure good convection in the electroforming solution. The dispersion of diamond grains and displacement of nickel ions are noticeably improved. A miniature funnel mould enables the diamond grains to converge towards the cathode to increase their deposition probability on the substrate, thereby improving their distribution on the substrate surface. A micro ZrO 2 ceramic ferrule is finely ground by the developed grinding tool and then yields a surface roughness of R a = 0.085 µm. The proposed approach is applied during the final machining process

  10. Minocycline enhances inhibitory transmission to substantia gelatinosa neurons of the rat spinal dorsal horn.

    Science.gov (United States)

    Peng, H-Z; Ma, L-X; Lv, M-H; Hu, T; Liu, T

    2016-04-05

    Minocycline, a second-generation tetracycline, is well known for its antibiotic, anti-inflammatory, and antinociceptive effects. Modulation of synaptic transmission is one of the analgesic mechanisms of minocycline. Although it has been reported that minocycline may suppress excitatory glutamatergic synaptic transmission, it remains unclear whether it could affect inhibitory synaptic transmission, which also plays a key role in modulating pain signaling. To examine the effect of minocycline on synaptic transmission in rat spinal substantia gelatinosa (SG) neurons, we recorded spontaneous inhibitory postsynaptic currents (sIPSCs) using whole-cell patch-clamp recording at a holding potential of 0 mV. Bath application of minocycline significantly increased the frequency but not the amplitude of sIPSCs in a reversible and concentration-dependent manner with an EC50 of 85. The enhancement of inhibitory synaptic transmission produced by minocycline was not affected by the glutamate receptor antagonists CNQX and D-APV or by the voltage-gated sodium channel blocker tetrodotoxin (TTX). Moreover, the potency of minocycline for facilitating sIPSC frequency was the same in both glycinergic and GABAergic sIPSCs without changing their decay phases. However, the facilitatory effect of minocycline on sIPSCs was eliminated in a Ca(2+)-free Krebs solution or by co-administration with calcium channel blockers. In summary, our data demonstrate that baseline inhibitory synaptic transmission in SG neurons is markedly enhanced by minocycline. This may function to decrease the excitability of SG neurons, thus leading to a modulation of nociceptive transmission. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Spontaneous compactification to homogeneous spaces

    International Nuclear Information System (INIS)

    Mourao, J.M.

    1988-01-01

    The spontaneous compactification of extra dimensions to compact homogeneous spaces is studied. The methods developed within the framework of coset space dimensional reduction scheme and the most general form of invariant metrics are used to find solutions of spontaneous compactification equations

  12. Detection of cryoglobulins in serum of Caspian miniature horse

    Directory of Open Access Journals (Sweden)

    Atyabi, N,

    2012-06-01

    Full Text Available Blood samples were collected from 20 healthy miniature Caspian horses at 37 °C. Isolation of cryoglobulin was performed based on a standard method in present study. Harvested sera were kept at 4 °C for two hours and then examined for cryoglubolin. Four serum samples containing precipitate Suspicious of containing cryoglobulin were selected. Subsequently serum protein electrophoresis was performed on normal serum samples and also on four serum samples containing precipitates using an automated electrophoresis system on cellulose acetate strips. In addition Ig isotypes detection (IgG, IgM and IgA was performed on both precipitates and serum containing precipitates using single radio immunediffusion method (SRID. A narrow-based peak on gamma region of precipitate acetate cellulose strips was observed. Precipitate concentrations were strikingly higher than normal concentration of serum immuneglobulins. It can be suggested that cryoglobulin concentration in a proportion of Caspian miniature horse is higher than other equides may be in relation with animal susceptibility to neoplasias such as lymphoma and leukemia.

  13. Miniaturized Optical Tweezers Through Fiber-End Microfabrication

    KAUST Repository

    Liberale, Carlo; Cojoc, Gheorghe; Rajamanickam, Vijayakumar; Ferrara, Lorenzo; Bragheri, Francesca; Minzioni, Paolo; Perozziello, Gerardo; Candeloro, Patrizio; Cristiani, Ilaria; Di Fabrizio, Enzo M.

    2014-01-01

    Optical tweezers represent a powerful tool for a variety of applications both in biology and in physics, and their miniaturization and full integration is of great interest so as to reduce size (towards portable systems), and to minimize the required intervention from the operator. Optical fibers represent a natural solution to achieve this goal, and here we review the realization of single-fiber optical tweezers able to create a purely optical three-dimensional trap. © Springer International Publishing Switzerland 2015.

  14. Miniaturized Optical Tweezers Through Fiber-End Microfabrication

    KAUST Repository

    Liberale, Carlo

    2014-07-30

    Optical tweezers represent a powerful tool for a variety of applications both in biology and in physics, and their miniaturization and full integration is of great interest so as to reduce size (towards portable systems), and to minimize the required intervention from the operator. Optical fibers represent a natural solution to achieve this goal, and here we review the realization of single-fiber optical tweezers able to create a purely optical three-dimensional trap. © Springer International Publishing Switzerland 2015.

  15. Calcification of the intervertebral discs and curvature of the radius and ulna: A radiographic survey of Finnish miniature dachshunds

    International Nuclear Information System (INIS)

    Lappalainen, A.; Norrgaard, M.; Alm, K.; Snellman, M.; Laitinen, O.

    2001-01-01

    The vertebral column of 124 randomly selected miniature dachshunds, representing 4.5% of the population registered by the Finnish Kennel Club during the years 1988 to 1996, were radiographed. The front legs were also radiographed in order to evaluate the curvature of the radius and ulna. Calcified discs were found in 75.9% of the longhaired miniature dachshunds and in 86.7% of the wirehaired ones. The occurrence of signs associated with IDD was 16.5% in longhaired and 15.6% in wirehaired miniature dachshunds. The occurrence of signs of IDD in dogs with calcified discs was 20.0% and 17.9% in longhaired and wirehaired miniature dachshunds, respectively. In dogs without calcifications only one dog showed signs of IDD. The curvature of the radius and the ulna did not differ between the dogs with signs of IDD and the healthy ones, or between the dogs with and without intervertebral calcifications. Our results indicate that radiographic eradication based on the presence of intervertebral calcifications is not suitable for breeding purposes for the Finnish miniature dachshund population because the percentage of dogs without calcifications is small

  16. Case of spontaneous ventriculocisternostomy

    Energy Technology Data Exchange (ETDEWEB)

    Yamane, Kanji; Yoshimoto, Hisanori; Harada, Kiyoshi; Uozumi, Tohru [Hiroshima Univ. (Japan). School of Medicine; Kuwabara, Satoshi

    1983-05-01

    The authors experienced a case of spontaneous ventriculocisternostomy diagnosed by CT scan with metrizamide and Conray. Patient was 23-year-old male who had been in good health until one month before admission, when he began to have headache and tinnitus. He noticed bilateral visual acuity was decreased about one week before admission and vomiting appeared two days before admission. He was admitted to our hospital because of bilateral papilledema and remarkable hydrocephalus diagnosed by CT scan. On admission, no abnormal neurological signs except for bilateral papilledema were noted. Immediately, right ventricular drainage was performed. Pressure of the ventricle was over 300mmH/sub 2/O and CSF was clear. PVG and PEG disclosed an another cavity behind the third ventricle, which was communicated with the third ventricle, and occlusion of aqueduct of Sylvius. Metrizamide CT scan and Conray CT scan showed a communication between this cavity and quadrigeminal and supracerebellar cisterns. On these neuroradiological findings, the diagnosis of obstructive hydrocephalus due to benign aqueduct stenosis accompanied with spontaneous ventriculocisternostomy was obtained. Spontaneous ventriculocisternostomy was noticed to produce arrest of hydrocephalus, but with our case, spontaneous regression of such symptoms did not appeared. By surgical ventriculocisternostomy (method by Torkildsen, Dandy, or Scarff), arrest of hydrocephalus was seen in about 50 to 70 per cent, which was the same results as those of spontaneous ventriculocisternostomy. It is concluded that VP shunt or VA shunt is thought to be better treatment of obstructive hydrocephalus than the various kinds of surgical ventriculocisternostomy.

  17. Spontaneous Intracranial Hypotension without Orthostatic Headache

    Directory of Open Access Journals (Sweden)

    Tülay Kansu

    2009-03-01

    Full Text Available We report 2 cases of spontaneous intracranial hypotension that presented with unilateral abducens nerve palsy, without orthostatic headache. While sixth nerve palsies improved without any intervention, subdural hematoma was detected with magnetic resonance imaging. We conclude that headache may be absent in spontaneous intracranial hypotension and spontaneous improvement of sixth nerve palsy can occur, even after the development of a subdural hematoma

  18. Miniature Bioprocess Array: A Platform for Quantitative Physiology and Bioprocess Optimization

    National Research Council Canada - National Science Library

    Keasling, Jay

    2002-01-01

    .... The miniature bioprocess array is based on an array of 150-microliters wells, each one of which incorporates MEMS for the closed-loop control of cell culture parameters such as temperature, pH, and dissolved oxygen...

  19. Spontaneous intraorbital hematoma: case report

    Directory of Open Access Journals (Sweden)

    Vinodan Paramanathan

    2010-12-01

    Full Text Available Vinodan Paramanathan, Ardalan ZolnourianQueen's Hospital NHS Foundation Trust, Burton on Trent, Staffordshire DE13 0RB, UKAbstract: Spontaneous intraorbital hematoma is an uncommon clinical entity seen in ophthalmology practice. It is poorly represented in the literature. Current evidence attributes it to orbital trauma, neoplasm, vascular malformations, acute sinusitis, and systemic abnormalities. A 65-year-old female presented with spontaneous intraorbital hematoma manifesting as severe ocular pains, eyelid edema, proptosis, and diplopia, without a history of trauma. Computer tomography demonstrated a fairly well defined extraconal lesion with opacification of the paranasal sinuses. The principal differential based on all findings was that of a spreading sinus infection and an extraconal tumor. An unprecedented finding of a spontaneous orbital hematoma was discovered when the patient was taken to theater. We discuss the rarity of this condition and its management.Keywords: hemorrhage, ophthalmology, spontaneous, intra-orbital, hematoma

  20. Development of a novel miniature detonation-driven shock tube assembly that uses in situ generated oxyhydrogen mixture

    International Nuclear Information System (INIS)

    Janardhanraj, S.; Jagadeesh, G.

    2016-01-01

    A novel concept to generate miniature shockwaves in a safe, repeatable, and controllable manner in laboratory confinements using an in situ oxyhydrogen generator has been proposed and demonstrated. This method proves to be more advantageous than existing methods because there is flexibility to vary strength of the shockwave, there is no need for storage of high pressure gases, and there is minimal waste disposal. The required amount of oxyhydrogen mixture is generated using alkaline electrolysis that produces hydrogen and oxygen gases in stoichiometric quantity. The rate of oxyhydrogen mixture production for the newly designed oxyhydrogen generator is found to be around 8 ml/s experimentally. The oxyhydrogen generator is connected to the driver section of a specially designed 10 mm square miniature shock tube assembly. A numerical code that uses CANTERA software package is used to predict the properties of the driver gas in the miniature shock tube. This prediction along with the 1-D shock tube theory is used to calculate the properties of the generated shockwave and matches reasonably well with the experimentally obtained values for oxyhydrogen mixture fill pressures less than 2.5 bars. The miniature shock tube employs a modified tri-clover clamp assembly to facilitate quick changing of diaphragm and replaces the more cumbersome nut and bolt system of fastening components. The versatile nature of oxyhydrogen detonation-driven miniature shock tube opens up new horizons for shockwave-assisted interdisciplinary applications.

  1. Development of a novel miniature detonation-driven shock tube assembly that uses in situ generated oxyhydrogen mixture

    Energy Technology Data Exchange (ETDEWEB)

    Janardhanraj, S.; Jagadeesh, G., E-mail: jaggie@aero.iisc.ernet.in [Department of Aerospace Engineering, Indian Institute of Science, Bangalore 560012 (India)

    2016-08-15

    A novel concept to generate miniature shockwaves in a safe, repeatable, and controllable manner in laboratory confinements using an in situ oxyhydrogen generator has been proposed and demonstrated. This method proves to be more advantageous than existing methods because there is flexibility to vary strength of the shockwave, there is no need for storage of high pressure gases, and there is minimal waste disposal. The required amount of oxyhydrogen mixture is generated using alkaline electrolysis that produces hydrogen and oxygen gases in stoichiometric quantity. The rate of oxyhydrogen mixture production for the newly designed oxyhydrogen generator is found to be around 8 ml/s experimentally. The oxyhydrogen generator is connected to the driver section of a specially designed 10 mm square miniature shock tube assembly. A numerical code that uses CANTERA software package is used to predict the properties of the driver gas in the miniature shock tube. This prediction along with the 1-D shock tube theory is used to calculate the properties of the generated shockwave and matches reasonably well with the experimentally obtained values for oxyhydrogen mixture fill pressures less than 2.5 bars. The miniature shock tube employs a modified tri-clover clamp assembly to facilitate quick changing of diaphragm and replaces the more cumbersome nut and bolt system of fastening components. The versatile nature of oxyhydrogen detonation-driven miniature shock tube opens up new horizons for shockwave-assisted interdisciplinary applications.

  2. Verification of a CT scanner using a miniature step gauge

    DEFF Research Database (Denmark)

    Cantatore, Angela; Andreasen, J.L.; Carmignato, S.

    2011-01-01

    The work deals with performance verification of a CT scanner using a 42mm miniature replica step gauge developed for optical scanner verification. Errors quantification and optimization of CT system set-up in terms of resolution and measurement accuracy are fundamental for use of CT scanning...

  3. Model-based tracking of miniaturized grippers using particle swarm optimization

    NARCIS (Netherlands)

    Scheggi, Stefano; Yoon, ChangKyu; Gracias, David H.; Misra, Sarthak

    2016-01-01

    Micro-sized agents can benefit robotic minimally invasive surgery since they can be inserted into the human body and use natural pathways such as arteries and veins or the gastrointestinal tract, to reach their target for drug delivery or diagnosis. Recently, miniaturized agents with shape-changing

  4. Screening for spontaneous preterm birth

    NARCIS (Netherlands)

    van Os, M.A.; van Dam, A.J.E.M.

    2015-01-01

    Preterm birth is the most important cause of perinatal morbidity and mortality worldwide. In this thesis studies on spontaneous preterm birth are presented. The main objective was to investigate the predictive capacity of mid-trimester cervical length measurement for spontaneous preterm birth in a

  5. Biosensing with Paper-Based Miniaturized Printed Electrodes–A Modern Trend

    Directory of Open Access Journals (Sweden)

    Célia M. Silveira

    2016-09-01

    Full Text Available From the bench-mark work on microfluidics from the Whitesides’s group in 2007, paper technology has experienced significant growth, particularly regarding applications in biomedical research and clinical diagnostics. Besides the structural properties supporting microfluidics, other advantageous features of paper materials, including their versatility, disposability and low cost, show off the great potential for the development of advanced and eco-friendly analytical tools. Consequently, paper was quickly employed in the field of electrochemical sensors, being an ideal material for producing custom, tailored and miniaturized devices. Stencil-, inkjet-, or screen-printing are the preferential techniques for electrode manufacturing. Not surprisingly, we witnessed a rapid increase in the number of publications on paper based screen-printed sensors at the turn of the past decade. Among the sensing strategies, various biosensors, coupling electrochemical detectors with biomolecules, have been proposed. This work provides a critical review and a discussion on the future progress of paper technology in the context of miniaturized printed electrochemical biosensors.

  6. Biosensing with Paper-Based Miniaturized Printed Electrodes–A Modern Trend

    Science.gov (United States)

    Silveira, Célia M.; Monteiro, Tiago; Almeida, Maria Gabriela

    2016-01-01

    From the bench-mark work on microfluidics from the Whitesides’s group in 2007, paper technology has experienced significant growth, particularly regarding applications in biomedical research and clinical diagnostics. Besides the structural properties supporting microfluidics, other advantageous features of paper materials, including their versatility, disposability and low cost, show off the great potential for the development of advanced and eco-friendly analytical tools. Consequently, paper was quickly employed in the field of electrochemical sensors, being an ideal material for producing custom, tailored and miniaturized devices. Stencil-, inkjet-, or screen-printing are the preferential techniques for electrode manufacturing. Not surprisingly, we witnessed a rapid increase in the number of publications on paper based screen-printed sensors at the turn of the past decade. Among the sensing strategies, various biosensors, coupling electrochemical detectors with biomolecules, have been proposed. This work provides a critical review and a discussion on the future progress of paper technology in the context of miniaturized printed electrochemical biosensors. PMID:27690119

  7. Biosensing with Paper-Based Miniaturized Printed Electrodes-A Modern Trend.

    Science.gov (United States)

    Silveira, Célia M; Monteiro, Tiago; Almeida, Maria Gabriela

    2016-09-28

    From the bench-mark work on microfluidics from the Whitesides's group in 2007, paper technology has experienced significant growth, particularly regarding applications in biomedical research and clinical diagnostics. Besides the structural properties supporting microfluidics, other advantageous features of paper materials, including their versatility, disposability and low cost, show off the great potential for the development of advanced and eco-friendly analytical tools. Consequently, paper was quickly employed in the field of electrochemical sensors, being an ideal material for producing custom, tailored and miniaturized devices. Stencil-, inkjet-, or screen-printing are the preferential techniques for electrode manufacturing. Not surprisingly, we witnessed a rapid increase in the number of publications on paper based screen-printed sensors at the turn of the past decade. Among the sensing strategies, various biosensors, coupling electrochemical detectors with biomolecules, have been proposed. This work provides a critical review and a discussion on the future progress of paper technology in the context of miniaturized printed electrochemical biosensors.

  8. Early pregnancy angiogenic markers and spontaneous abortion

    DEFF Research Database (Denmark)

    Andersen, Louise B; Dechend, Ralf; Karumanchi, S Ananth

    2016-01-01

    BACKGROUND: Spontaneous abortion is the most commonly observed adverse pregnancy outcome. The angiogenic factors soluble Fms-like kinase 1 and placental growth factor are critical for normal pregnancy and may be associated to spontaneous abortion. OBJECTIVE: We investigated the association between...... maternal serum concentrations of soluble Fms-like kinase 1 and placental growth factor, and subsequent spontaneous abortion. STUDY DESIGN: In the prospective observational Odense Child Cohort, 1676 pregnant women donated serum in early pregnancy, gestational week ..., interquartile range 71-103). Concentrations of soluble Fms-like kinase 1 and placental growth factor were determined with novel automated assays. Spontaneous abortion was defined as complete or incomplete spontaneous abortion, missed abortion, or blighted ovum

  9. Moessbauer study of miniature vessels from the Sican burial site of Huaca Loro

    Energy Technology Data Exchange (ETDEWEB)

    Cervantes, G., E-mail: gabriela.cervantes@pucp.pe [Pontificia Universidad Catolica del Peru (Peru); Shimada, I. [Southern Illinois University (United States); Haeusler, W.; Wagner, U.; Wagner, F. E. [Technische Universitaet Muenchen, Physik-Department E15 (Germany)

    2011-11-15

    Small handmade ceramic vessels are often found in large quantities in late pre-hispanic elite tombs on the north coast of Peru. These miniature vessels are of poor artistic and technologic qualities compared with other offerings found in tombs and have not received much attention. Our hypothesis is that these miniatures were made hastily by non-elite funeral attendants, which resulted in the observed formal and material variability. Here we report on the results of a systematic archaeological analysis of the shape and of archaeometric analyses by Moessbauer spectroscopy and XRD of the firing conditions of such vessels that were conducted to test the above hypothesis.

  10. Miniature solid-state gas compressor

    Science.gov (United States)

    Lawless, W.N.; Cross, L.E.; Steyert, W.A.

    1985-05-07

    A miniature apparatus for compressing gases is disclosed in which an elastomer disposed between two opposing electrostrictive or piezoelectric ceramic blocks, or between a single electrostrictive or piezoelectric ceramic block and a rigid surface, is caused to extrude into or recede from a channel defined adjacent to the elastomer in response to application or removal of an electric field from the blocks. Individual cells of blocks and elastomer are connected to effect a gas compression by peristaltic activation of the individual cells. The apparatus is self-valving in that the first and last cells operate as inlet and outlet valves, respectively. Preferred electrostrictive and piezoelectric ceramic materials are disclosed, and an alternative, non-peristaltic embodiment of the apparatus is described. 9 figs.

  11. High-Frequency Flush Mounted Miniature LOX Fiber-Optic Pressure Sensor, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Luna Innovations is teaming with the University of Alabama, Huntsville, to develop a miniature flush-mounted fiber-optic pressure sensor that will allow accurate,...

  12. Analytical and Finite Element Modeling of Nanomembranes for Miniaturized, Continuous Hemodialysis

    Directory of Open Access Journals (Sweden)

    Tucker Burgin

    2015-12-01

    Full Text Available Hemodialysis involves large, periodic treatment doses using large-area membranes. If the permeability of dialysis membranes could be increased, it would reduce the necessary dialyzer size and could enable a wearable device that administers a continuous, low dose treatment of chronic kidney disease. This paper explores the application of ultrathin silicon membranes to this purpose, by way of analytical and finite element models of diffusive and convective transport of plasma solutes during hemodialysis, which we show to be predictive of experimental results. A proof-of-concept miniature nanomembrane dialyzer design is then proposed and analytically predicted to clear uremic toxins at near-ideal levels, as measured by several markers of dialysis adequacy. This work suggests the feasibility of miniature nanomembrane-based dialyzers that achieve therapeutic levels of uremic toxin clearance for patients with kidney failure.

  13. Spontaneous emission by moving atoms

    International Nuclear Information System (INIS)

    Meystre, P.; Wilkens, M.

    1994-01-01

    It is well known that spontaneous emission is not an intrinsic atomic property, but rather results from the coupling of the atom to the vacuum modes of the electromagnetic field. As such, it can be modified by tailoring the electromagnetic environment into which the atom can radiate. This was already realized by Purcell, who noted that the spontaneous emission rate can be enhanced if the atom placed inside a cavity is resonant with one of the cavity is resonant with one of the cavity modes, and by Kleppner, who discussed the opposite case of inhibited spontaneous emission. It has also been recognized that spontaneous emission need not be an irreversible process. Indeed, a system consisting of a single atom coupled to a single mode of the electromagnetic field undergoes a periodic exchange of excitation between the atom and the field. This periodic exchange remains dominant as long as the strength of the coupling between the atom and a cavity mode is itself dominant. 23 refs., 6 figs

  14. The effect of gamma radiation on the stability of miniature reference electrodes

    International Nuclear Information System (INIS)

    Galuszka-Muga, B.; Muga, M.L.; Hanrahan, R.J.

    2006-01-01

    The design and fabrication of four types of miniature reference electrodes and their long term stability in a radiation field are described. Miniature versions of a saturated calomel electrode (MSCE), a silver/silver chloride electrode (MAG), a tungsten/tungsten oxide (MWO) and a copper/copper ion (MCU) electrode were tested in a 10 kGy/h (1 Mrad/h) radiation field for up to 30 days total at 25 and 40 o C. The latter two (MWO and MCU) varied appreciably over time periods of several hours whereas the former two (MSCE and MAG) varied less than 1 mV over periods of 6-8 h and are deemed suitable as reference electrodes for corrosion studies of systems immersed in a radiation field at elevated temperature

  15. A low-power and high-precision miniaturized digital sun sensor

    NARCIS (Netherlands)

    Boer, B.M. de; Durkut, M.

    2013-01-01

    A prototype miniaturized digital sun sensor (miniDSS) was developed by TNO. It is expected to be launched on QuadSat for in-orbit demonstration. The single-chip sun sensor comprises an application specific integrated circuit (ASIC) on which an active pixel sensor (APS), read-out and processing

  16. A Case of Multiple Spontaneous Keloid Scars

    Directory of Open Access Journals (Sweden)

    Abdulhadi Jfri

    2015-07-01

    Full Text Available Keloid scars result from an abnormal healing response to cutaneous injury or inflammation that extends beyond the borders of the original wound. Spontaneous keloid scars forming in the absence of any previous trauma or surgical procedure are rare. Certain syndromes have been associated with this phenomenon, and few reports have discussed the evidence of single spontaneous keloid scar, which raises the question whether they are really spontaneous. Here, we present a 27-year-old mentally retarded single female with orbital hypertelorism, broad nasal bridge, repaired cleft lip and high-arched palate who presented with progressive multiple spontaneous keloid scars in different parts of her body which were confirmed histologically by the presence of typical keloidal collagen. This report supports the fact that keloid scars can appear spontaneously and are possibly linked to a genetic factor. Furthermore, it describes a new presentation of spontaneous keloid scars in the form of multiple large lesions in different sites of the body.

  17. Miniaturized Planar Room Temperature Ionic Liquid Electrochemical Gas Sensor for Rapid Multiple Gas Pollutants Monitoring.

    Science.gov (United States)

    Wan, Hao; Yin, Heyu; Lin, Lu; Zeng, Xiangqun; Mason, Andrew J

    2018-02-01

    The growing impact of airborne pollutants and explosive gases on human health and occupational safety has escalated the demand of sensors to monitor hazardous gases. This paper presents a new miniaturized planar electrochemical gas sensor for rapid measurement of multiple gaseous hazards. The gas sensor features a porous polytetrafluoroethylene substrate that enables fast gas diffusion and room temperature ionic liquid as the electrolyte. Metal sputtering was utilized for platinum electrodes fabrication to enhance adhesion between the electrodes and the substrate. Together with carefully selected electrochemical methods, the miniaturized gas sensor is capable of measuring multiple gases including oxygen, methane, ozone and sulfur dioxide that are important to human health and safety. Compared to its manually-assembled Clark-cell predecessor, this sensor provides better sensitivity, linearity and repeatability, as validated for oxygen monitoring. With solid performance, fast response and miniaturized size, this sensor is promising for deployment in wearable devices for real-time point-of-exposure gas pollutant monitoring.

  18. Combinatorial Modulation of Signaling Pathways Reveals Cell-Type-Specific Requirements for Highly Efficient and Synchronous iPSC Reprogramming

    Directory of Open Access Journals (Sweden)

    Simon E. Vidal

    2014-10-01

    Full Text Available The differentiated state of somatic cells provides barriers for the derivation of induced pluripotent stem cells (iPSCs. To address why some cell types reprogram more readily than others, we studied the effect of combined modulation of cellular signaling pathways. Surprisingly, inhibition of transforming growth factor β (TGF-β together with activation of Wnt signaling in the presence of ascorbic acid allows >80% of murine fibroblasts to acquire pluripotency after 1 week of reprogramming factor expression. In contrast, hepatic and blood progenitors predominantly required only TGF-β inhibition or canonical Wnt activation, respectively, to reprogram at efficiencies approaching 100%. Strikingly, blood progenitors reactivated endogenous pluripotency loci in a highly synchronous manner, and we demonstrate that expression of specific chromatin-modifying enzymes and reduced TGF-β/mitogen-activated protein (MAP kinase activity are intrinsic properties associated with the unique reprogramming response of these cells. Our observations define cell-type-specific requirements for the rapid and synchronous reprogramming of somatic cells.

  19. Distinct kinetics of inhibitory currents in thalamocortical neurons that arise from dendritic or axonal origin.

    Directory of Open Access Journals (Sweden)

    Sunggu Yang

    Full Text Available Thalamocortical neurons in the dorsal lateral geniculate nucleus (dLGN transfer visual information from retina to primary visual cortex. This information is modulated by inhibitory input arising from local interneurons and thalamic reticular nucleus (TRN neurons, leading to alterations of receptive field properties of thalamocortical neurons. Local GABAergic interneurons provide two distinct synaptic outputs: axonal (F1 terminals and dendritic (F2 terminals onto dLGN thalamocortical neurons. By contrast, TRN neurons provide only axonal output (F1 terminals onto dLGN thalamocortical neurons. It is unclear if GABAA receptor-mediated currents originating from F1 and F2 terminals have different characteristics. In the present study, we examined multiple characteristics (rise time, slope, halfwidth and decay τ of GABAA receptor-mediated miniature inhibitory postsynaptic synaptic currents (mIPSCs originating from F1 and F2 terminals. The mIPSCs arising from F2 terminals showed slower kinetics relative to those from F1 terminals. Such differential kinetics of GABAAR-mediated responses could be an important role in temporal coding of visual signals.

  20. Ballistic tongue projection in a miniaturized salamander.

    Science.gov (United States)

    Deban, Stephen M; Bloom, Segall V

    2018-05-20

    Miniaturization of body size is often accompanied by peculiarities in morphology that can have functional consequences. We examined the feeding behavior and morphology of the miniaturized plethodontid salamander Thorius, one of the smallest vertebrates, to determine if its performance and biomechanics differ from those of its larger relatives. High-speed imaging and dynamics analysis of feeding at a range of temperatures show that tongue projection in Thorius macdougalli is ballistic and achieves accelerations of up to 600 G with low thermal sensitivity, indicating that tongue projection is powered by an elastic-recoil mechanism. Preceding ballistic projection is an unusual preparatory phase of tongue protrusion, which, like tongue retraction, shows lower performance and higher thermal sensitivity that are indicative of movement being powered directly by muscle shortening. The variability of tongue-projection kinematics and dynamics is comparable to larger ballistic-tongued plethodontids and reveals that Thorius is capable of modulating its tongue movements in response to prey distance. Morphological examination revealed that T. macdougalli possesses a reduced number of myofibers in the tongue muscles, a large projector muscle mass relative to tongue mass, and an unusual folding of the tongue skeleton, compared with larger relatives. Nonetheless, T. macdougalli retains the elaborated collagen aponeuroses in the projector muscle that store elastic energy and a tongue skeleton that is free of direct myofiber insertion, two features that appear to be essential for ballistic tongue projection in salamanders. © 2018 Wiley Periodicals, Inc.

  1. Capillary filling of miniaturized sources for electrospray mass spectrometry

    International Nuclear Information System (INIS)

    Arscott, Steve; Gaudet, Matthieu; Brinkmann, Martin; Ashcroft, Alison E; Blossey, Ralf

    2006-01-01

    Capillary slot-based emitter tips are a novel tool for use in electrospray ionization-mass spectrometry of large biomolecules. We have performed a combined theoretical and experimental study of capillary filling in micron-sized slots with the aim of developing a rational design procedure for miniaturized electrospray sources, ultimately enabling the integration of ESI into laboratory-on-a-chip devices

  2. Release of fission products from miniature fuel plates at elevated temperature

    International Nuclear Information System (INIS)

    Posey, J.C.

    1982-01-01

    Three miniature fuel plates were tested at progressively higher temperatures. A U 3 Si plated blistered and released fission gases at 500 0 C. Two U 3 O 8 filled plates blistered and released fission gases at 550 0 C

  3. Flame-in-gas-shield and miniature diffusion flame hydride atomizers for atomic fluorescence spectrometry: optimization and comparison

    International Nuclear Information System (INIS)

    Marschner, Karel; Musil, Stanislav; Dědina, Jiří

    2015-01-01

    A detailed optimization of relevant experimental parameters of two hydride atomizers for atomic fluorescence spectrometry: flame-in-gas-shield atomizer with a two-channel shielding unit and a standard atomizer for atomic fluorescence spectrometry, miniature diffusion flame, was performed. Arsine, generated by the reaction with NaBH 4 in a flow injection arrangement, was chosen as the model hydride. Analytical characteristics of both the atomizers (sensitivity, noise, limits of detection) were compared. Under optimum conditions sensitivity obtained with flame-in-gas-shield atomizer was approximately twice higher than with miniature diffusion flame. The additional advantage of flame-in-gas-shield atomizer is significantly lower flame emission resulting in a better signal to noise ratio. The resulting arsenic limits of detection for miniature diffusion flame and flame-in-gas-shield atomizer were 3.8 ng l −1 and 1.0 ng l −1 , respectively. - Highlights: • We optimized and compared two hydride atomizers for atomic fluorescence spectrometry. • Miniature diffusion flame and flame-in-gas-shield atomizer were optimized. • The limit of detection for arsenic was 1.0 ng l −1

  4. Flame-in-gas-shield and miniature diffusion flame hydride atomizers for atomic fluorescence spectrometry: optimization and comparison

    Energy Technology Data Exchange (ETDEWEB)

    Marschner, Karel, E-mail: karel.marschner@biomed.cas.cz [Institute of Analytical Chemistry of the ASCR, v. v. i., Veveří 97, 602 00 Brno (Czech Republic); Charles University in Prague, Faculty of Science, Department of Analytical Chemistry, Albertov 8, 128 43 Prague (Czech Republic); Musil, Stanislav; Dědina, Jiří [Institute of Analytical Chemistry of the ASCR, v. v. i., Veveří 97, 602 00 Brno (Czech Republic)

    2015-07-01

    A detailed optimization of relevant experimental parameters of two hydride atomizers for atomic fluorescence spectrometry: flame-in-gas-shield atomizer with a two-channel shielding unit and a standard atomizer for atomic fluorescence spectrometry, miniature diffusion flame, was performed. Arsine, generated by the reaction with NaBH{sub 4} in a flow injection arrangement, was chosen as the model hydride. Analytical characteristics of both the atomizers (sensitivity, noise, limits of detection) were compared. Under optimum conditions sensitivity obtained with flame-in-gas-shield atomizer was approximately twice higher than with miniature diffusion flame. The additional advantage of flame-in-gas-shield atomizer is significantly lower flame emission resulting in a better signal to noise ratio. The resulting arsenic limits of detection for miniature diffusion flame and flame-in-gas-shield atomizer were 3.8 ng l{sup −1} and 1.0 ng l{sup −1}, respectively. - Highlights: • We optimized and compared two hydride atomizers for atomic fluorescence spectrometry. • Miniature diffusion flame and flame-in-gas-shield atomizer were optimized. • The limit of detection for arsenic was 1.0 ng l{sup −1}.

  5. Miniature Ground Penetrating Radar, CRUX GPR

    Science.gov (United States)

    Kim, Soon Sam; Carnes, Steven R.; Haldemann, Albert F.; Ulmer, Christopher T.; Ng, Eddie; Arcone, Steven A.

    2006-01-01

    Under NASA instrument development programs (PIDDP 2000-2002, MIPD 2003-2005, ESR and T, 2005) we have been developing miniature ground penetrating radars (GPR) for use in mapping subsurface stratigraphy from planetary rovers for Mars and lunar applications. The Mars GPR is for deeper penetration (up to 50 m depth) into the Martian subsurface at moderate resolution (0.5 m) for a geological characterization. As a part of the CRUX (Construction and Resource Utilization Explorer) instrument suite, the CRUX GPR is optimized for a lunar prospecting application. It will have shallower penetration (5 m depth) with higher resolution (10 cm) for construction operations including ISRU (in-situ resource utilization).

  6. Uniform LED illuminator for miniature displays

    Science.gov (United States)

    Medvedev, Vladimir; Pelka, David G.; Parkyn, William A.

    1998-10-01

    The Total Internally Reflecting (TIR) lens is a faceted structure composed of prismatic elements that collect a source's light over a much larger angular range than a conventional Fresnel lens. It has been successfully applied to the efficient collimation of light from incandescent and fluorescent lamps, and from light-emitting diodes (LEDs). A novel LED-powered collimating backlight is presented here, for uniformly illuminating 0.25'-diagonal miniature liquid- crystal displays, which are a burgeoning market for pagers, cellular phones, digital cameras, camcorders, and virtual- reality displays. The backlight lens consists of a central dual-asphere refracting section and an outer TIR section, properly curved with a curved exit face.

  7. The laboratory test rig with miniature jet engine to research aviation fuels combustion process

    Directory of Open Access Journals (Sweden)

    Gawron Bartosz

    2015-12-01

    Full Text Available This article presents laboratory test rig with a miniature turbojet engine (MiniJETRig – Miniature Jet Engine Test Rig, that was built in the Air Force Institute of Technology. The test rig has been developed for research and development works aimed at modelling and investigating processes and phenomena occurring in full scale jet engines. In the article construction of a test rig is described, with a brief discussion on the functionality of each of its main components. Additionally examples of measurement results obtained during the realization of the initial tests have been included, presenting the capabilities of the test rig.

  8. Spontaneous pneumothorax in silicotuberculosis of lung

    International Nuclear Information System (INIS)

    Kolenic, J.; Jurgova, T.; Zimacek, J.; Vajo, J.; Krchnavy, M.

    1995-01-01

    The authors describe the case of 62 years old man with the appearance of spontaneous pneumothorax, in whom the basic pulmonary disease was silicotuberculosis of the lung. At clinic of occupational diseases in Kosice have been evidence 965 cases of silicosis and silicotuberculosis. From 1971 they have now the first case of spontaneous pneumothorax. The authors make discussion about possible mechanical and biochemical factors, which cause relatively low incidence of spontaneous pneumothorax in silicosis of the lung. (authors)

  9. Fabrication of applicator system of miniature X-ray tube based on carbon nanotubes for a skin cancer therapy

    International Nuclear Information System (INIS)

    Park, Han Beom; Kim, Hyun Jin; Lee, Ju Hyuk; Ha, Jun Mok; Cho, Sung Oh

    2016-01-01

    A miniature X-ray tube is a small X-ray generation device generally with a diameter of less than 10 mm. Because of the feasible installation in a spatially constrained area and the possibility of electrical on/off control, miniature X-ray tubes can be widely used for nondestructive X-ray radiography, hand held X-ray spectrometers, electric brachytherapy, and interstitial or intracavitary radiation therapy or imaging with the substitution of radioactive isotopes. Miniature X-ray tubes have been developed mostly using thermionic electron sources or secondary X-ray emission. The X-ray tube show excellent field emission properties and good X-ray spectrum. Also, the flattening filter was made to irradiate uniformly. The X-ray dose radial uniformities between installed flattening filter and non-installed flattening filter were measured. When flattening filter is equipped, X-ray uniformity was improved from higher than 20% to lower than 10%. As a result, the fabricated applicator system of the miniature X-ray tube using optimized flattening filter exhibited fairly excellent properties

  10. Laser weld reconstitution of conventional Charpy and Miniaturized Notch Test (MNT) specimens

    International Nuclear Information System (INIS)

    Manahan, M.P.; Williams, J.; Martukanitz, R.P.

    1993-01-01

    As nuclear power plants approach end-of-license (EOL) and consideration is given to license renewal, there is an ever increasing need to expand the amount of data obtainable from the original surveillance specimens. A laser welding technique to reconstitute broken Charpy specimens is being developed to produce both conventional and miniaturized Charpy specimens. This paper reports on early laser welding development efforts and summarizes previous proof-of-principle experiments on a 1/16 scale miniaturized Charpy test. In order to benchmark the laser welding procedure, the laser-reconstituted specimen data have been compared with the original specimen data. In addition, the microstructure after welding has been examined to ensure that the material in the vicinity of the notch is essentially unchanged after the welding process. Data which characterize the thermal transient during welding are obtained by attaching thermocouples to the specimens. Other important considerations include perturbation of the stress field near the notch, dynamic stress waves, and contact of the weld region with the tup. Precise control of welding parameters has been demonstrated, heat-affected zones as small as 0.25 mm can be achieved, and sufficient penetration depth can be obtained to enable welding thick sections (1T or greater) to yield conventional Charpy specimens or fracture toughness specimens and thin sections (∼5 mm) to yield Miniaturized Notch Test (MNT) specimens

  11. High power VCSELs for miniature optical sensors

    Science.gov (United States)

    Geske, Jon; Wang, Chad; MacDougal, Michael; Stahl, Ron; Follman, David; Garrett, Henry; Meyrath, Todd; Snyder, Don; Golden, Eric; Wagener, Jeff; Foley, Jason

    2010-02-01

    Recent advances in Vertical-cavity Surface-emitting Laser (VCSEL) efficiency and packaging have opened up alternative applications for VCSELs that leverage their inherent advantages over light emitting diodes and edge-emitting lasers (EELs), such as low-divergence symmetric emission, wavelength stability, and inherent 2-D array fabrication. Improvements in reproducible highly efficient VCSELs have allowed VCSELs to be considered for high power and high brightness applications. In this talk, Aerius will discuss recent advances with Aerius' VCSELs and application of these VCSELs to miniature optical sensors such as rangefinders and illuminators.

  12. Spontaneous pneumothorax in diffuse cystic lung diseases.

    Science.gov (United States)

    Cooley, Joseph; Lee, Yun Chor Gary; Gupta, Nishant

    2017-07-01

    Diffuse cystic lung diseases (DCLDs) are a heterogeneous group of disorders with varying pathophysiologic mechanisms that are characterized by the presence of air-filled lung cysts. These cysts are prone to rupture, leading to the development of recurrent spontaneous pneumothoraces. In this article, we review the epidemiology, clinical features, and management DCLD-associated spontaneous pneumothorax, with a focus on lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome, and pulmonary Langerhans cell histiocytosis. DCLDs are responsible for approximately 10% of apparent primary spontaneous pneumothoraces. Computed tomography screening for DCLDs (Birt-Hogg-Dubé syndrome, lymphangioleiomyomatosis, and pulmonary Langerhans cell histiocytosis) following the first spontaneous pneumothorax has recently been shown to be cost-effective and can help facilitate early diagnosis of the underlying disorders. Patients with DCLD-associated spontaneous pneumothorax have a very high rate of recurrence, and thus pleurodesis should be considered following the first episode of spontaneous pneumothorax in these patients, rather than waiting for a recurrent episode. Prior pleurodesis is not a contraindication to future lung transplant. Although DCLDs are uncommon, spontaneous pneumothorax is often the sentinel event that provides an opportunity for diagnosis. By understanding the burden and implications of pneumothoraces in DCLDs, clinicians can facilitate early diagnosis and appropriate management of the underlying disorders.

  13. Dimensional and Structural Control of Silica Aerogel Membranes for Miniaturized Motionless Gas Pumps.

    Science.gov (United States)

    Zhao, Shanyu; Jiang, Bo; Maeder, Thomas; Muralt, Paul; Kim, Nayoung; Matam, Santhosh Kumar; Jeong, Eunho; Han, Yen-Lin; Koebel, Matthias M

    2015-08-26

    With growing public interest in portable electronics such as micro fuel cells, micro gas total analysis systems, and portable medical devices, the need for miniaturized air pumps with minimal electrical power consumption is on the rise. Thus, the development and downsizing of next-generation thermal transpiration gas pumps has been investigated intensively during the last decades. Such a system relies on a mesoporous membrane that generates a thermomolecular pressure gradient under the action of an applied temperature bias. However, the development of highly miniaturized active membrane materials with tailored porosity and optimized pumping performance remains a major challenge. Here we report a systematic study on the manufacturing of aerogel membranes using an optimized, minimal-shrinkage sol-gel process, leading to low thermal conductivity and high air conductance. This combination of properties results in superior performance for miniaturized thermomolecular air pump applications. The engineering of such aerogel membranes, which implies pore structure control and chemical surface modification, requires both chemical processing know-how and a detailed understanding of the influence of the material properties on the spatial flow rate density. Optimal pumping performance was found for devices with integrated membranes with a density of 0.062 g cm(-3) and an average pore size of 142.0 nm. Benchmarking of such low-density hydrophobic active aerogel membranes gave an air flow rate density of 3.85 sccm·cm(-2) at an operating temperature of 400 °C. Such a silica aerogel membrane based system has shown more than 50% higher pumping performance when compared to conventional transpiration pump membrane materials as well as the ability to withstand higher operating temperatures (up to 440 °C). This study highlights new perspectives for the development of miniaturized thermal transpiration air pumps while offering insights into the fundamentals of molecular pumping in

  14. Scaling laws for free piston Stirling engine design: Benefits and challenges of miniaturization

    International Nuclear Information System (INIS)

    Formosa, Fabien; Fréchette, Luc G.

    2013-01-01

    This work explores the scaling effects for FPSE (free piston Stirling engines), which are known for their simple architecture and potentially high thermodynamic performances. Scaling laws are given and their potential for miniaturization is highlighted. A simple model which allows the design of the geometrical parameters of the heat exchangers, the regenerator and the masses of the pistons is proposed. It is based on the definition of six characteristic dimensionless groups. They are derived from the physics underlying the behavior of the free piston Stirling machine and their relevancy is backed up by comparisons between documented Stirling engines from the literature. Keeping constant values for each group throughout the scaling range theoretically ensures constant performance. The main losses of Stirling engine (heat conduction loss, reheat loss in the regenerator, pressure drop and gas-spring hysteresis) can be expressed as a function of the geometrical and operating parameters. Additionally, the consequences of leakage due to the manufacturing precision of pistons architectures are underlined. From the proposed scaling laws, potential power and efficiency of Stirling cycle engines at a millimeter scale can be anticipated. It appears that the power density increases with miniaturization. It is also shown that the dynamic masses related to the engine size are increased when scaling down and that the gap leakage presents the highest detrimental effects on the efficiency. These results call for dedicated architectures for micro-engines. - Highlights: • Similitude strategy is applied to Stirling engines and allows preliminary design. • New scaling laws are derived. • The power density can be increased with miniaturization. • The gap between the piston and casing is highly detrimental to the performances. • High engine operating pressure is required when miniaturizing

  15. The scaling of performance and losses in miniature internal combustion engines

    Science.gov (United States)

    Menon, Shyam Kumar

    Miniature glow ignition internal combustion (IC) piston engines are an off--the--shelf technology that could dramatically increase the endurance of miniature electric power supplies and the range and endurance of small unmanned air vehicles provided their overall thermodynamic efficiencies can be increased to 15% or better. This thesis presents the first comprehensive analysis of small (system is developed that is capable of making reliable measurements of engine performance and losses in these small engines. Methodologies are also developed for measuring volumetric, heat transfer, exhaust, mechanical, and combustion losses. These instruments and techniques are used to investigate the performance of seven single-cylinder, two-stroke, glow fueled engines ranging in size from 15 to 450 g (0.16 to 7.5 cm3 displacement). Scaling rules for power output, overall efficiency, and normalized power are developed from the data. These will be useful to developers of micro-air vehicles and miniature power systems. The data show that the minimum length scale of a thermodynamically viable piston engine based on present technology is approximately 3 mm. Incomplete combustion is the most important challenge as it accounts for 60-70% of total energy losses. Combustion losses are followed in order of importance by heat transfer, sensible enthalpy, and friction. A net heat release analysis based on in-cylinder pressure measurements suggest that a two--stage combustion process occurs at low engine speeds and equivalence ratios close to 1. Different theories based on burning mode and reaction kinetics are proposed to explain the observed results. High speed imaging of the combustion chamber suggests that a turbulent premixed flame with its origin in the vicinity of the glow plug is the primary driver of combustion. Placing miniature IC engines on a turbulent combustion regime diagram shows that they operate in the 'flamelet in eddy' regime whereas conventional--scale engines operate

  16. FEL gain optimisation and spontaneous radiation

    Energy Technology Data Exchange (ETDEWEB)

    Bali, L.M.; Srivastava, A.; Pandya, T.P. [Lucknow Univ. (India)] [and others

    1995-12-31

    Colson have evaluated FEL gains for small deviations from perfect electron beam injection, with radiation of the same polarisation as that of the wiggler fields. We find that for optimum gain the polarisation of the optical field should be the same as that of the spontaneous emission under these conditions. With a helical wiggler the axial oscillations resulting from small departures from perfect electron beam injection lead to injection dependent unequal amplitudes and phases of the spontaneous radiation in the two transverse directions. Viewed along the axis therefore the spontaneous emission is elliptically polarised. The azimuth of the ellipse varies with the difference of phase of the two transverse components of spontaneous emission but the eccentricity remains the same. With planar wigglers the spontaneous emission viewed in the axial direction is linearly polarised, again with an injection dependent azimuth. For optimum coherent gain of a radiation field its polarisation characteristics must be the same as those of the spontaneous radiation with both types of wiggler. Thus, with a helical wiggler and the data reported earlier, an increase of 10% in the FEL gain at the fundamental frequency and of 11% at the fifth harmonic has been calculated in the small gain per pass limit. Larger enhancements in gain may result from more favourable values of input parameters.

  17. Release of fission products from miniature fuel plates at elevated temperature

    International Nuclear Information System (INIS)

    Posey, John C.

    1983-01-01

    Three miniature fuel plates were tested at progressively higher temperatures. A U 3 Si filled plate blistered and released fission gases at 500 deg. C. Two U 3 O 8 filled plates blistered and released fission gases at 550 deg. C. (author)

  18. Robust and adaptive band-to-band image transform of UAS miniature multi-lens multispectral camera

    Science.gov (United States)

    Jhan, Jyun-Ping; Rau, Jiann-Yeou; Haala, Norbert

    2018-03-01

    Utilizing miniature multispectral (MS) or hyperspectral (HS) cameras by mounting them on an Unmanned Aerial System (UAS) has the benefits of convenience and flexibility to collect remote sensing imagery for precision agriculture, vegetation monitoring, and environment investigation applications. Most miniature MS cameras adopt a multi-lens structure to record discrete MS bands of visible and invisible information. The differences in lens distortion, mounting positions, and viewing angles among lenses mean that the acquired original MS images have significant band misregistration errors. We have developed a Robust and Adaptive Band-to-Band Image Transform (RABBIT) method for dealing with the band co-registration of various types of miniature multi-lens multispectral cameras (Mini-MSCs) to obtain band co-registered MS imagery for remote sensing applications. The RABBIT utilizes modified projective transformation (MPT) to transfer the multiple image geometry of a multi-lens imaging system to one sensor geometry, and combines this with a robust and adaptive correction (RAC) procedure to correct several systematic errors and to obtain sub-pixel accuracy. This study applies three state-of-the-art Mini-MSCs to evaluate the RABBIT method's performance, specifically the Tetracam Miniature Multiple Camera Array (MiniMCA), Micasense RedEdge, and Parrot Sequoia. Six MS datasets acquired at different target distances and dates, and locations are also applied to prove its reliability and applicability. Results prove that RABBIT is feasible for different types of Mini-MSCs with accurate, robust, and rapid image processing efficiency.

  19. Spontaneous Bacterial Peritonitis in Subclinical Hypothyroidism

    Directory of Open Access Journals (Sweden)

    Dalip Gupta

    2013-11-01

    Full Text Available Hypothyroidism is an uncommon cause of ascites. Here we describe a case of a 75 year-old female patient with spontaneous bacterial peritonitis and subclinical hypothyroidism that resolved with thyroid replacement and antibiotic therapy respectively. Ascitic fluid analysis revealed a gram-positive bacterium on gram staining. A review of the literature revealed just one other reported case of myxoedema ascites with concomitant spontaneous bacterial peritonitis and no case has till been reported of spontaneous bacterial peritonitis in subclinical hypothyroidism.

  20. Patient-specific induced pluripotent stem cells (iPSCs) for the study and treatment of retinal degenerative diseases.

    Science.gov (United States)

    Wiley, Luke A; Burnight, Erin R; Songstad, Allison E; Drack, Arlene V; Mullins, Robert F; Stone, Edwin M; Tucker, Budd A

    2015-01-01

    Vision is the sense that we use to navigate the world around us. Thus it is not surprising that blindness is one of people's most feared maladies. Heritable diseases of the retina, such as age-related macular degeneration and retinitis pigmentosa, are the leading cause of blindness in the developed world, collectively affecting as many as one-third of all people over the age of 75, to some degree. For decades, scientists have dreamed of preventing vision loss or of restoring the vision of patients affected with retinal degeneration through drug therapy, gene augmentation or a cell-based transplantation approach. In this review we will discuss the use of the induced pluripotent stem cell technology to model and develop various treatment modalities for the treatment of inherited retinal degenerative disease. We will focus on the use of iPSCs for interrogation of disease pathophysiology, analysis of drug and gene therapeutics and as a source of autologous cells for cell transplantation and replacement. Copyright © 2014. Published by Elsevier Ltd.

  1. Miniature Packaging Concept for LNAs in the 200-300 GHz Range

    Science.gov (United States)

    Samoska, Lorene; Fung, Andy; Varonen, Mikko; Lin, Robert; Peralta, Alejandro; Soria, Mary; Lee, Choonsup; Padmanabhan, Sharmila; Sarkozy, Stephen; Lai, Richard

    2016-01-01

    In this work, we describe new miniaturized low noise amplifier modules which we developed for incorporation in small-scale satellites or Cubesats, and which exhibit similar or better performance compared to previously reported LNAs in the literature. We have targeted the WR4 (170-260 GHz) and WR3 (220-325 GHz) waveguide bands for the module development. The modules include two different methods of E-plane probes which have been developed for low loss, and stability at high frequencies. MMIC LNAs were also developed for these frequency ranges and fabricated in Northrop Grumman Corporation's 35 nm InP HEMT technology, and we have experimentally verified that noise performance is lower than reported in prior work. The best results include a miniature LNA module with 550K noise at 224 GHz, and a wideband LNA module with 15 dB gain from 230-280 GHz.

  2. Fabrication of a miniaturized cell using microsystem technologies for electrochemical applications

    International Nuclear Information System (INIS)

    Lakard, Boris; Jeannot, Jean-Claude; Spajer, Michel; Herlem, Guillaume; Labachelerie, Michel de; Blind, Pascal; Fahys, Bernard

    2005-01-01

    A new type of electrochemical cell has been developed for use in electrochemical, chemical and biological applications. Using a platinum microelectrode as working electrode, this cell incorporates a silver microelectrode as reference electrode. These microelectrodes, whose area is equal to 1 μm 2 , were fabricated using photolithography, sputtering, and focused ion beam (FIB) technologies since these micro-fabrication techniques allow us to develop miniaturized electrochemical cells useful either for nanoelectrochemistry or biosensors applications. In this study, we show it is possible to coat a surface by chemical or biological compounds by immersing the microelectrodes in a solution, then setting a difference of potential between the two microelectrodes of the cell. For example, we used this miniaturized cell to realize the electrochemical polymerization of aniline into polyaniline to show that this electrochemical cell is efficient to coat a surface with a thin film of polymer

  3. Spontaneous mutation rates and the rate-doubling dose

    International Nuclear Information System (INIS)

    Von Borstel, R.C.; Moustaccki, E.; Latarjet, R.

    1978-01-01

    The amount of radiation required to double the frequency of mutations or tumours over the rate of those that occur spontaneously is called the rate-doubling dose. An equivalent concept has been proposed for exposure to other environmental mutagens. The doubling dose concept is predicated on the assumption that all human populations have the same spontaneous mutation rate, and that this spontaneous mutation rate is known. It is now established for prokaryotes and lower eukaryotes that numerous genes control the spontaneous mutation rate, and it is likely that the same is true for human cells as well. Given that the accepted mode of evolution of human populatons is from small, isolated groups of individuals, it seems likely that each population would have a different spontaneous mutation rate. Given that a minimum of twenty genes control or affect the spontaneous mutation rate, and that each of these in turn is susceptible to spontaneously arising or environmentally induced mutations, it seems likely that every individual within a population (except for siblings from identical multiple births) will have a unique spontaneous mutation rate. If each individual in a population does have a different spontaneous mutation rate, the doubling dose concept, in rigorous terms, is fallacious. Therefore, as with other concepts of risk evaluation, the doubling dose concept is subject to criticism. Nevertheless, until we know individual spontaneous mutation rates with precision, and can evaluate risks based on this information, the doubling dose concept has a heuristic value and is needed for practical assessment of risks for defined populations. (author)

  4. Characterization of a novel miniaturized burst-mode infrared laser system for IR-MALDESI mass spectrometry imaging.

    Science.gov (United States)

    Ekelöf, Måns; Manni, Jeffrey; Nazari, Milad; Bokhart, Mark; Muddiman, David C

    2018-03-01

    Laser systems are widely used in mass spectrometry as sample probes and ionization sources. Mid-infrared lasers are particularly suitable for analysis of high water content samples such as animal and plant tissues, using water as a resonantly excited sacrificial matrix. Commercially available mid-IR lasers have historically been bulky and expensive due to cooling requirements. This work presents a novel air-cooled miniature mid-IR laser with adjustable burst-mode output and details an evaluation of its performance for mass spectrometry imaging. The miniature laser was found capable of generating sufficient energy for complete ablation of animal tissue in the context of an IR-MALDESI experiment with exogenously added ice matrix, yielding several hundred confident metabolite identifications. Graphical abstract The use of a novel miniature 2.94 μm burst-mode laser in IR-MALDESI allows for rapid and sensitive mass spectrometry imaging of a whole mouse.

  5. Fundamental studies on miniature dose meter using variable capacitance Si-diode

    International Nuclear Information System (INIS)

    Inoue, Yoshio

    1976-01-01

    The results of fundamental studies on development of a miniature dose meter using a semiconductor applicable for dosimetry in both intracavitary and external radiotherapy are described. Many different instruments have been applied in clinical dosimetry for regional lesions, mostly in phantom studies, e. g. the small sized ionization chamber, the fluoroluminescence glass dose meter and the thermoluminescence dose meter. However, there are considerable problems regarding safety, reproducibility, and simplicity for regional dosimetry of intracavitary lesions, such as genitourinary, gastrointestinal and respiratory malignancies. To overcome these problems, an attempt was made to develop a miniature catheter type detector using a variable capacitance Si-diode for gamma ray dosimetry. The newly developed miniature dose meter using a semiconductor has the following characteristics. As the tip of detector (23mm long and 3mm in diameter) is very small, the apparatus unit is easy to manipulate in the dosimetry of intracavitary lesions. As no voltage is supplied to the detector, there is no danger of electric shock from in vivo studies. A strict linearity existed between the radiation dose rate and the generated voltage even when the range of experimental irradiation dose rate was extremely wide. The sensitivity of the detector was affected by the environmental temperature, but it was easy to correct the sensitivity by applying a special calibration chart to the value derived from a thermister enclosed in the detector. Even with the experimental irradiation of more than 50,000R, no changes in the sensitivity of the detector were observed. Thus, the durability of the apparatus was shown to be excellent. (auth.)

  6. Development of a miniature multiple reference optical coherence tomography imaging device

    Science.gov (United States)

    McNamara, Paul M.; O'Riordan, Colm; Collins, Seán.; O'Brien, Peter; Wilson, Carol; Hogan, Josh; Leahy, Martin J.

    2016-03-01

    Multiple reference optical coherence tomography (MR-OCT) is a new technology ideally suited to low-cost, compact OCT imaging. This modality is an extension of time-domain OCT with the addition of a partial mirror in front of the reference mirror. This enables extended, simultaneous depth scanning with the relatively short sweep of a miniature voice coil motor on which the scanning mirror is mounted. Applications of this technology include biometric security, ophthalmology, personal health monitoring and non-destructive testing. This work details early-stage development of the first iteration of a miniature MR-OCT device. This device utilizes a fiber-coupled input from an off-board superluminescent diode (SLD). Typical dimensions of the module are 40 × 57 mm, but future designs are expected to be more compact. Off-the-shelf miniature optical components, voice coil motors and photodetectors are used, with the complexity of design depending on specific applications. The photonic module can be configured as either polarized or non-polarized and can include balanced detection. The photodetectors are directly connected to a printed circuit board under the module containing a transimpedance amplifier with complimentary outputs. The results shown in this work are from the non-polarized device. Assembly of the photonic modules requires extensive planning. In choosing the optical components, Zemax simulations are performed to model the beam characteristics. The physical layout is modeled using Solidworks and each component is placed and aligned via a well-designed alignment procedure involving an active-alignment pick-and-place assembly system.

  7. Evaluation of miniature tension specimen fabrication techniques and performance

    International Nuclear Information System (INIS)

    Hamilton, M.L.; Blotter, M.A.; Edwards, D.J.

    1993-01-01

    The confident application of miniature tensile specimens requires adequate control over their fabrication and is facilitated by automated test and analysis techniques. Three fabrication processes -- punching, chemical milling, and electrical discharge machining (EDM) -- were recently evaluated, leading to the replacement of the previously used punching technique with a wire EDM technique. The automated data acquisition system was upgraded, and an interactive data analysis program was developed

  8. Evaluation of miniature tensile specimen fabrication techniques and performance

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, M.L. (Pacific Northwest Lab., Richland, WA (United States)); Blotter, M.A.; Edwards, D.J. (Missouri Univ., Rolla, MO (United States))

    1992-01-01

    The confident application of miniature tensile specimens requires adequate control over their fabrication and is facilitated by automated test and analysis techniques. Three fabrication processes -- punching, chemical, milling, and electrical discharge machining (EDM) -- were recently evaluated, leading to the replacement of the previously used punching technique with a wire EDM technique. The automated data acquisition system was upgraded, and an interactive data analysis program was developed.

  9. Evaluation of miniature tensile specimen fabrication techniques and performance

    International Nuclear Information System (INIS)

    Hamilton, M.L.; Blotter, M.A.; Edwards, D.J.

    1992-01-01

    The confident application of miniature tensile specimens requires adequate control over their fabrication and is facilitated by automated test and analysis techniques. Three fabrication processes -- punching, chemical, milling, and electrical discharge machining (EDM) -- were recently evaluated, leading to the replacement of the previously used punching technique with a wire EDM technique. The automated data acquisition system was upgraded, and an interactive data analysis program was developed

  10. Modeling the Pathogenesis of Charcot-Marie-Tooth Disease Type 1A Using Patient-Specific iPSCs

    Directory of Open Access Journals (Sweden)

    Lei Shi

    2018-01-01

    Full Text Available Charcot-Marie-Tooth disease type 1A (CMT1A, one of the most frequent inherited peripheral neuropathies, is associated with PMP22 gene duplication. Previous studies of CMT1A mainly relied on rodent models, and it is not yet clear how PMP22 overexpression leads to the phenotype in patients. Here, we generated the human induced pluripotent stem cell (hiPSC lines from two CMT1A patients as an in vitro cell model. We found that, unlike the normal control cells, CMT1A hiPSCs rarely generated Schwann cells through neural crest stem cells (NCSCs. Instead, CMT1A NCSCs produced numerous endoneurial fibroblast-like cells in the Schwann cell differentiation system, and similar results were obtained in a PMP22-overexpressing iPSC model. Therefore, despite the demyelination-remyelination and/or dysmyelination theory for CMT1A pathogenesis, developmental disabilities of Schwann cells may be considered as an underlying cause of CMT1A. Our results may have important implications for the uncovering of the underlying mechanism and the development of a promising therapeutic strategy for CMT1A neuropathy.

  11. Design of high voltage power supply of miniature X-ray tube based on resonant Royer

    International Nuclear Information System (INIS)

    Liu Xiyao; Zeng Guoqiang; Tan Chengjun; Luo Qun; Gong Chunhui; Huang Rui

    2013-01-01

    Background: In recent years, X rays are widely used in various fields. With the rapid development of national economy, the demand of high quality, high reliability, and high stability miniature X-ray tube has grown rapidly. As an important core component of miniature X-ray tube, high voltage power supply has attracted wide attention. Purpose: To match miniature, the high voltage power supply should be small, lightweight, good quality, etc. Based on the basic performance requirements of existing micro-X-ray tube high voltage power supply, this paper designs an output from 0 to -30 kV adjustable miniature X-ray tube voltage DC power supply. Compared to half-bridge and full-bridge switching-mode power supply, its driving circuit is simple. With working on the linear condition, it has no switching noise. Methods: The main circuit makes use of DC power supply to provide the energy. The resonant Royer circuit supplies sine wave which drives to the high frequency transformer's primary winding with resultant sine-like high voltage appearing across the secondary winding. Then, the voltage doubling rectifying circuit would achieve further boost. In the regulator circuit, a feedback control resonant transistor base current is adopted. In order to insulate air, a silicone rubber is used for high pressure part packaging, and the output voltage is measured by the dividing voltage below -5 kV. Results: The stability of circuit is better than 0.2%/6 h and the percent of the output ripple voltage is less than 0.3%. Keeping the output voltage constant, the output current can reach 57 μA by changing the size of load resistor. This high voltage power supply based on resonant Royer can meet the requirement of miniature X-ray tube. Conclusions: The circuit can satisfy low noise, low ripple, low power and high voltage regulator power supply design. However, its efficiency is not high enough because of the linear condition. In the next design, to further reduce power consumption, we

  12. Visually Evoked Spiking Evolves While Spontaneous Ongoing Dynamics Persist

    Science.gov (United States)

    Huys, Raoul; Jirsa, Viktor K.; Darokhan, Ziauddin; Valentiniene, Sonata; Roland, Per E.

    2016-01-01

    Neurons in the primary visual cortex spontaneously spike even when there are no visual stimuli. It is unknown whether the spiking evoked by visual stimuli is just a modification of the spontaneous ongoing cortical spiking dynamics or whether the spontaneous spiking state disappears and is replaced by evoked spiking. This study of laminar recordings of spontaneous spiking and visually evoked spiking of neurons in the ferret primary visual cortex shows that the spiking dynamics does not change: the spontaneous spiking as well as evoked spiking is controlled by a stable and persisting fixed point attractor. Its existence guarantees that evoked spiking return to the spontaneous state. However, the spontaneous ongoing spiking state and the visual evoked spiking states are qualitatively different and are separated by a threshold (separatrix). The functional advantage of this organization is that it avoids the need for a system reorganization following visual stimulation, and impedes the transition of spontaneous spiking to evoked spiking and the propagation of spontaneous spiking from layer 4 to layers 2–3. PMID:26778982

  13. A new stoichiometric miniaturization strategy for screening of industrial microbial strains: application to cellulase hyper-producing Trichoderma reesei strains

    Directory of Open Access Journals (Sweden)

    Jourdier Etienne

    2012-05-01

    Full Text Available Abstract Background During bioprocess development, secondary screening is a key step at the boundary between laboratory and industrial conditions. To ensure an effective high-throughput screening, miniaturized laboratory conditions must mimic industrial conditions, especially for oxygen transfer, feeding capacity and pH stabilization. Results A feeding strategy has been applied to develop a simple screening procedure, in which a stoichiometric study is combined with a standard miniaturization procedure. Actually, the knowledge of all nutriments and base or acid requirements leads to a great simplification of pH stabilization issue of miniaturized fed-batch cultures. Applied to cellulase production by Trichoderma reesei, this strategy resulted in a stoichiometric mixed feed of carbon and nitrogen sources. While keeping the pH between shake flask and stirred bioreactor comparable, the developed shake flask protocol reproduced the strain behaviour under stirred bioreactor conditions. Compared to a an already existing miniaturized shake flasks protocol, the cellulase concentration was increased 5-fold, reaching about 10 g L-1. Applied to the secondary screening of several clones, the newly developed protocol succeeded in selecting a clone with a high industrial potential. Conclusions The understanding of a bioprocess stoichiometry contributed to define a simpler and more effective miniaturization. The suggested strategy can potentially be applied to other fed-batch processes, for the screening of either strain collections or experimental conditions.

  14. Peritonitis - spontaneous bacterial

    Science.gov (United States)

    Spontaneous bacterial peritonitis (SBP); Ascites - peritonitis; Cirrhosis - peritonitis ... who are on peritoneal dialysis for kidney failure. Peritonitis may have other causes . These include infection from ...

  15. A Novel Protocol for Directed Differentiation of C9orf72-Associated Human Induced Pluripotent Stem Cells Into Contractile Skeletal Myotubes.

    Science.gov (United States)

    Swartz, Elliot W; Baek, Jaeyun; Pribadi, Mochtar; Wojta, Kevin J; Almeida, Sandra; Karydas, Anna; Gao, Fen-Biao; Miller, Bruce L; Coppola, Giovanni

    2016-11-01

    : Induced pluripotent stem cells (iPSCs) offer an unlimited resource of cells to be used for the study of underlying molecular biology of disease, therapeutic drug screening, and transplant-based regenerative medicine. However, methods for the directed differentiation of skeletal muscle for these purposes remain scarce and incomplete. Here, we present a novel, small molecule-based protocol for the generation of multinucleated skeletal myotubes using eight independent iPSC lines. Through combinatorial inhibition of phosphoinositide 3-kinase (PI3K) and glycogen synthase kinase 3β (GSK3β) with addition of bone morphogenic protein 4 (BMP4) and fibroblast growth factor 2 (FGF2), we report up to 64% conversion of iPSCs into the myogenic program by day 36 as indicated by MYOG + cell populations. These cells began to exhibit spontaneous contractions as early as 34 days in vitro in the presence of a serum-free medium formulation. We used this protocol to obtain iPSC-derived muscle cells from frontotemporal dementia (FTD) patients harboring C9orf72 hexanucleotide repeat expansions (rGGGGCC), sporadic FTD, and unaffected controls. iPSCs derived from rGGGGCC carriers contained RNA foci but did not vary in differentiation efficiency when compared to unaffected controls nor display mislocalized TDP-43 after as many as 120 days in vitro. This study presents a rapid, efficient, and transgene-free method for generating multinucleated skeletal myotubes from iPSCs and a resource for further modeling the role of skeletal muscle in amyotrophic lateral sclerosis and other motor neuron diseases. Protocols to produce skeletal myotubes for disease modeling or therapy are scarce and incomplete. The present study efficiently generates functional skeletal myotubes from human induced pluripotent stem cells using a small molecule-based approach. Using this strategy, terminal myogenic induction of up to 64% in 36 days and spontaneously contractile myotubes within 34 days were achieved

  16. Bio-inspired Miniature Suction Cups Actuated by Shape Memory Alloy

    Directory of Open Access Journals (Sweden)

    Hu Bing-shan

    2010-02-01

    Full Text Available Wall climbing robots using negative pressure suction always employ air pumps which have great noise and large volume. Two prototypes of bio-inspired miniature suction cup actuated by shape memory alloy (SMA are designed based on studying characteristics of biologic suction apparatuses, and the suction cups in this paper can be used as adhesion mechanisms for miniature wall climbing robots without air pumps. The first prototype with a two-way shape memory effect (TWSME extension TiNi spring imitates the piston structure of the stalked sucker; the second one actuated by a one way SMA actuator with a bias has a basic structure of stiff margin, guiding element, leader and elastic element. Analytical model of the second prototype is founded considering the constitutive model of the SMA actuator, the deflection of the thin elastic plate under compound load and the thermo-dynamic model of the sealed air cavity. Experiments are done to test their suction characteristics, and the analytical model of the second prototype is simulated on Matlab/simulink platform and validated by experiments.

  17. Bio-inspired Miniature Suction Cups Actuated by Shape Memory Alloy

    Directory of Open Access Journals (Sweden)

    Hu Bing-Shan

    2009-09-01

    Full Text Available Wall climbing robots using negative pressure suction always employ air pumps which have great noise and large volume. Two prototypes of bio-inspired miniature suction cup actuated by shape memory alloy (SMA are designed based on studying characteristics of biologic suction apparatuses, and the suction cups in this paper can be used as adhesion mechanisms for miniature wall climbing robots without air pumps. The first prototype with a two-way shape memory effect (TWSME extension TiNi spring imitates the piston structure of the stalked sucker; the second one actuated by a one way SMA actuator with a bias has a basic structure of stiff margin, guiding element, leader and elastic element. Analytical model of the second prototype is founded considering the constitutive model of the SMA actuator, the deflection of the thin elastic plate under compound load and the thermo-dynamic model of the sealed air cavity. Experiments are done to test their suction characteristics, and the analytical model of the second prototype is simulated on Matlab/simulink platform and validated by experiments.

  18. Miniaturized radioisotope solid state power sources

    Science.gov (United States)

    Fleurial, J.-P.; Snyder, G. J.; Patel, J.; Herman, J. A.; Caillat, T.; Nesmith, B.; Kolawa, E. A.

    2000-01-01

    Electrical power requirements for the next generation of deep space missions cover a wide range from the kilowatt to the milliwatt. Several of these missions call for the development of compact, low weight, long life, rugged power sources capable of delivering a few milliwatts up to a couple of watts while operating in harsh environments. Advanced solid state thermoelectric microdevices combined with radioisotope heat sources and energy storage devices such as capacitors are ideally suited for these applications. By making use of macroscopic film technology, microgenrators operating across relatively small temperature differences can be conceptualized for a variety of high heat flux or low heat flux heat source configurations. Moreover, by shrinking the size of the thermoelements and increasing their number to several thousands in a single structure, these devices can generate high voltages even at low power outputs that are more compatible with electronic components. Because the miniaturization of state-of-the-art thermoelectric module technology based on Bi2Te3 alloys is limited due to mechanical and manufacturing constraints, we are developing novel microdevices using integrated-circuit type fabrication processes, electrochemical deposition techniques and high thermal conductivity substrate materials. One power source concept is based on several thermoelectric microgenerator modules that are tightly integrated with a 1.1W Radioisotope Heater Unit. Such a system could deliver up to 50mW of electrical power in a small lightweight package of approximately 50 to 60g and 30cm3. An even higher degree of miniaturization and high specific power values (mW/mm3) can be obtained when considering the potential use of radioisotope materials for an alpha-voltaic or a hybrid thermoelectric/alpha-voltaic power source. Some of the technical challenges associated with these concepts are discussed in this paper. .

  19. Search for spontaneous fission of 226Ra and systematics of the spontaneous fission, α-decay and cluster decay probabilities

    International Nuclear Information System (INIS)

    Mikheev, V.L.; Tret'yakova, S.P.; Golovchenko, A.N.; Timofeeva, O.V.; Hussonnois, M.; Le Naour, C.

    1998-01-01

    The low limit of the 226 Ra spontaneous fission half-life corresponding to T 1/2 ≥ 4 · 10 18 years is measured. The 226 Ra spontaneous fission probability proved to be about 50 times less than the value expected from the known systematics, connecting the ratios of theα-decay and spontaneous fission probabilities with the fissility parameter Z 2 /A. It is shown that the probabilities of spontaneous fission, α-decay and cluster decay can be systematized in the same way according to the difference between the decay products Coulomb energy near the scission point and decay energy Q

  20. Dorsomedial prefontal cortex supports spontaneous thinking per se.

    Science.gov (United States)

    Raij, T T; Riekki, T J J

    2017-06-01

    Spontaneous thinking, an action to produce, consider, integrate, and reason through mental representations, is central to our daily experience and has been suggested to serve crucial adaptive purposes. Such thinking occurs among other experiences during mind wandering that is associated with activation of the default mode network among other brain circuitries. Whether and how such brain activation is linked to the experience of spontaneous thinking per se remains poorly known. We studied 51 healthy subjects using a comprehensive experience-sampling paradigm during 3T functional magnetic resonance imaging. In comparison with fixation, the experiences of spontaneous thinking and spontaneous perception were related to activation of wide-spread brain circuitries, including the cortical midline structures, the anterior cingulate cortex and the visual cortex. In direct comparison of the spontaneous thinking versus spontaneous perception, activation was observed in the anterior dorsomedial prefrontal cortex. Modality congruence of spontaneous-experience-related brain activation was suggested by several findings, including association of the lingual gyrus with visual in comparison with non-verbal-non-visual thinking. In the context of current literature, these findings suggest that the cortical midline structures are involved in the integrative core substrate of spontaneous thinking that is coupled with other brain systems depending on the characteristics of thinking. Furthermore, involvement of the anterior dorsomedial prefrontal cortex suggests the control of high-order abstract functions to characterize spontaneous thinking per se. Hum Brain Mapp 38:3277-3288, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  1. Solid intraocular xanthogranuloma in three Miniature Schnauzer dogs.

    Science.gov (United States)

    Zarfoss, Mitzi K; Dubielzig, Richard R

    2007-01-01

    Macrophages that contain abundant intracytoplasmic lipid are called 'foam cells'. In four canine globes submitted to the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW), foam cells formed a solid intraocular mass. The purpose of this study was to describe the histopathologic findings in these cases. The electronic COPLOW database (1993-2006) was searched for the diagnosis of 'foam cell tumor'. Clinical history, gross pathology and histopathology (5-micron sections, hematoxylin and eosin and Alcian blue periodic acid Schiff) were reviewed in all cases. Cases were included if the globe was grossly filled by a solid mass and if all intraocular structures were effaced by lipid-laden foam cell macrophages admixed with birefringent, Alcian blue-positive crystals oriented in stellate patterns. All three patients (four globes) satisfying the selection criteria were Miniature Schnauzers. In all cases the clinical history included diabetes mellitus, hyperlipidemia and chronic bilateral uveitis that was interpreted to be lens-induced. All globes were enucleated because of glaucoma. The term solid intraocular xanthogranuloma was used to describe these cases because the intraocular contents were effaced by a solid mass of foam cells and birefringent crystals. The cases in this report suggest that diabetic Miniature Schnauzers with hyperlipidemia are at risk for lipid and macrophage-rich uveitis, which may in some cases form a solid inflammatory intraocular mass, precipitate glaucoma, and lead to enucleation.

  2. Maternal smoking predicts the risk of spontaneous abortion

    DEFF Research Database (Denmark)

    Nielsen, Ann; Hannibal, Charlotte Gerd; Lindekilde, Bodil Eriksen

    2006-01-01

    BACKGROUND: Few studies have examined smoking prior to pregnancy and the occurrence of spontaneous abortion, as most studies have addressed the risk of spontaneous abortion in relation to smoking during pregnancy. However, results are not entirely consistent. The aim of the present study...... was to assess the risk of spontaneous abortion considering smoking prior to pregnancy. METHODS: We performed a nested case-control study using prospective data from a population-based cohort comprising 11,088 women aged 20-29 years. From this cohort, women who experienced either a spontaneous abortion (n=343......) or who gave birth (n=1,578) during follow-up were selected. Associations between self-reported smoking at enrollment and subsequent spontaneous abortion were analyzed by means of multiple logistic regression. RESULTS: The risk of spontaneous abortion in relation to pre-pregnancy smoking showed a clear...

  3. Dexamethasone rapidly increases GABA release in the dorsal motor nucleus of the vagus via retrograde messenger-mediated enhancement of TRPV1 activity.

    Directory of Open Access Journals (Sweden)

    Andrei V Derbenev

    Full Text Available Glucocorticoids influence vagal parasympathetic output to the viscera via mechanisms that include modulation of neural circuitry in the dorsal vagal complex, a principal autonomic regulatory center. Glucocorticoids can modulate synaptic neurotransmitter release elsewhere in the brain by inducing release of retrograde signalling molecules. We tested the hypothesis that the glucocorticoid agonist dexamethasone (DEX modulates GABA release in the rat dorsal motor nucleus of the vagus (DMV. Whole-cell patch-clamp recordings revealed that DEX (1-10 µM rapidly (i.e. within three minutes increased the frequency of tetrodotoxin-resistant, miniature IPSCs (mIPSCs in 67% of DMV neurons recorded in acutely prepared slices. Glutamate-mediated mEPSCs were also enhanced by DEX (10 µM, and blockade of ionotropic glutamate receptors reduced the DEX effect on mIPSC frequency. Antagonists of type I or II corticosteroid receptors blocked the effect of DEX on mIPSCs. The effect was mimicked by application of the membrane-impermeant BSA-conjugated DEX, and intracellular blockade of G protein function with GDP βS in the recorded cell prevented the effect of DEX. The enhancement of GABA release was blocked by the TRPV1 antagonists, 5'-iodoresiniferatoxin or capsazepine, but was not altered by the cannabinoid type 1 receptor antagonist AM251. The DEX effect was prevented by blocking fatty acid amide hydrolysis or by inhibiting anandamide transport, implicating involvement of the endocannabinoid system in the response. These findings indicate that DEX induces an enhancement of GABA release in the DMV, which is mediated by activation of TRPV1 receptors on afferent terminals. The effect is likely induced by anandamide or other 'endovanilloid', suggesting activation of a local retrograde signal originating from DMV neurons to enhance synaptic inhibition locally in response to glucocorticoids.

  4. Osteonecrosis or spontaneous fractures following renal transplantation

    International Nuclear Information System (INIS)

    Andresen, J.; Nielsen, H.E.; Aarhus Univ.

    1981-01-01

    31 renal transplant recipients with posttransplant development of osteonecrosis or spontaneous fractures were evaluated with regard to age, duration of dialysis before transplantation. Determination of metacarpal bone mass at the time of transplantation and registration of bone resorption and soft tissue calcification at the time of transplantation and at the time of onset of osteonecrosis and spontaneous fractures were made. Apart from the increased mean age in patients with spontaneous fractures no difference was seen between the groups. Osteonecrosis and spontaneous fractures occurred in areas of trabecular bone. It seems most likely that after renal transplantation the patients show bone complications of different localization. (orig.) [de

  5. A novel miniature superconducting converter for 1 kA magnets

    NARCIS (Netherlands)

    Chevtchenko, O.A.; Krooshoop, Hendrikus J.G.; ten Kate, Herman H.J.; Fedorovsky, Michael A.

    1996-01-01

    A miniature full-wave converter to control the current of a superconducting magnet is developed and tested in our institutes. Typical design values of the device are: AC voltage of 35 V, current of 7 A, and frequency 50-60 Hz; DC voltage o f f 0.2 V, and current of * 1 kA. An efficiency is better

  6. Reduction of degraded events in miniaturized proportional counters

    Energy Technology Data Exchange (ETDEWEB)

    Plaga, R.; Kirsten, T. (Max Planck Inst. fuer Kernphysik, Heidelberg (Germany))

    1991-11-15

    A method to reduce the number of degraded events in miniaturized proportional counters is described. A shaping of the outer cathode leads to a more uniform gas gain along the counter axis. The method is useful in situations in which the total number of decay events is very low. The effects leading to degraded events are studied theoretically and experimentally. The usefulness of the method is demonstrated by using it for the proportional counter of the GALLEX solar neutrino experiment. (orig.).

  7. Miniaturized and general purpose fiber optic ultrasonic sources

    International Nuclear Information System (INIS)

    Biagi, E.; Fontani, S.; Masotti, L.; Pieraccini, M.

    1997-01-01

    Innovative photoacoustic sources for ultrasonic NDE, smart structure, and clinical diagnosis are proposed. The working principle is based on thermal conversion of laser pulses into a metallic film evaporated directly onto the tip of a fiber optic. Unique features of the proposed transducers are very high miniaturization and potential easy embedding in smart structure. Additional advantages, high bedding in smart structure. Additional advantages, high ultrasonic frequency, large and flat bandwidth. All these characteristics make the proposed device an ideal ultrasonic source

  8. High-Frequency Flush Mounted Miniature LOX Fiber-Optic Pressure Sensor II, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Luna Innovations has teamed with the University of Alabama, Huntsville, to develop a miniature flush-mounted fiber-optic pressure sensor that will allow accurate,...

  9. Pneumocystis carinii in the miniature dachshund: case report and literature review

    International Nuclear Information System (INIS)

    Lobetti, R.G.; Leisewitz, A.L.; Spencer, J.A.

    1996-01-01

    This article reviews Pneumocystis carinii and presents four cases in the miniature dachshund. The cases presented with hyperpnoea, tachypnoea and exercise intolerance. There were also clinical signs suggestive of immune incompetence in all the dogs. P carinii pneumonia was diagnosed in all four cases on transtracheal aspirate cytology. Immunological studies showed low globulin levels on serum electrophoresis, decreased lymphoblast transformation response (in the two cases that were tested) and a deficiency of immunoglobulins A, G and M. Light and electron microscopy as well as anti-canine immunoglobulin G immunoperoxidase staining studies were performed on one case which had died because of the disease. From these four cases, it appears that P carinii pneumonia in the miniature dachshund may be the result of an immunodeficiency. It does not, however, appear to be a classic primary severe combined immunodeficiency syndrome as the dogs appeared to respond to treatment, did not show growth failure and did not manifest overwhelming commensurate bacterial infections

  10. Examination system utilizing ionizing radiation and a flexible, miniature radiation detector probe

    Science.gov (United States)

    Majewski, Stanislaw; Kross, Brian J.; Zorn, Carl J.; Majewski, Lukasz A.

    1996-01-01

    An optimized examination system and method based on the Reverse Geometry X-Ray.RTM. (RGX.RTM.) radiography technique are presented. The examination system comprises a radiation source, at least one flexible, miniature radiation detector probe positioned in appropriate proximity to the object to be examined and to the radiation source with the object located between the source and the probe, a photodetector device attachable to an end of the miniature radiation probe, and a control unit integrated with a display device connected to the photodetector device. The miniature radiation detector probe comprises a scintillation element, a flexible light guide having a first end optically coupled to the scintillation element and having a second end attachable to the photodetector device, and an opaque, environmentally-resistant sheath surrounding the flexible light guide. The probe may be portable and insertable, or may be fixed in place within the object to be examined. An enclosed, flexible, liquid light guide is also presented, which comprises a thin-walled flexible tube, a liquid, preferably mineral oil, contained within the tube, a scintillation element located at a first end of the tube, closures located at both ends of the tube, and an opaque, environmentally-resistant sheath surrounding the flexible tube. The examination system and method have applications in non-destructive material testing for voids, cracks, and corrosion, and may be used in areas containing hazardous materials. In addition, the system and method have applications for medical and dental imaging.

  11. A Case of Spontaneously Resolved Bilateral Primary Spontaneous Pneumothorax

    Directory of Open Access Journals (Sweden)

    Hasan Kahraman

    2014-03-01

    Full Text Available A condition of intrapleural air-space accumulation in individuals without any history of trauma or lung disease is called as primary spontaneous pneumothorax (PSP. Sixteen-years-old male patient admitted with complains of chest pain and dyspnea beginning 3 day ago. On physical examination, severity of breath sounds decreased on right side. Chest radiograph was taken and right-sided pneumothorax was detected and tube thoracostomy was inserted. Two months ago the patient referred to a doctor with similar complaints and physical examination and chest radiograph were reported as normal. The radiograph was retrospectively examined and bilateral PSP was detected. We presented the case duo to spontaneous recovery of bilateral PSP is seen very rarely and so contributes data to the literature. In patients admitted to the clinic with chest pain and shortness of breath, pneumothorax should be considered at differential diagnosis.

  12. Maternal underweight and the risk of spontaneous abortion

    DEFF Research Database (Denmark)

    Helgstrand, Stine; Andersen, Anne-Marie Nybo

    2005-01-01

    BACKGROUND: To evaluate the risk of spontaneous abortion in relation to maternal pre-pregnant underweight. METHODS: The study was designed as a cohort study within the framework of the Danish National Birth Cohort (DNBC). The participants were a total of 23 821 women recruited consecutively...... spontaneous abortion. Relative risk of spontaneous abortion was calculated as Hazard Ratios using Cox regression with delayed entry. RESULTS: The outcome measure was spontaneous abortion. The hazard ratio for spontaneous abortion in women with a pre-pregnant body mass index (BMI) below 18.5 was 1.24 (95......% confidence limits 0.95-1.63) compared to women with pre-pregnant BMI 18.5-24.9. Women with a BMI of 25 or more had a smaller increase in risk of spontaneous abortion. Adjustment for maternal age, parity, previous miscarriages, and lifestyle factors did not affect the estimates substantially, neither did...

  13. Design of a Ku band miniature multiple beam klystron

    Energy Technology Data Exchange (ETDEWEB)

    Bandyopadhyay, Ayan Kumar, E-mail: ayan.bandyopadhyay@gmail.com; Pal, Debasish; Kant, Deepender [Microwave Tubes Division, CSIR-CEERI, Pilani, Rajasthan-333031 (India); Saini, Anil; Saha, Sukalyan; Joshi, Lalit Mohan

    2016-03-09

    The design of a miniature multiple beam klystron (MBK) working in the Ku-band frequency range is presented in this article. Starting from the main design parameters, design of the electron gun, the input and output couplers and radio frequency section (RF-section) are presented. The design methodology using state of the art commercial electromagnetic design tools, analytical formulae as well as noncommercial design tools are briefly presented in this article.

  14. A miniature concentrating photovoltaic and thermal system

    International Nuclear Information System (INIS)

    Kribus, Abraham; Kaftori, Daniel; Mittelman, Gur; Hirshfeld, Amir; Flitsanov, Yuri; Dayan, Abraham

    2006-01-01

    A novel miniature concentrating PV (MCPV) system is presented and analyzed. The system is producing both electrical and thermal energy, which is supplied to a nearby consumer. In contrast to PV/thermal (PV/T) flat collectors, the heat from an MCPV collector is not limited to low-temperature applications. The work reported here refers to the evaluation and preliminary design of the MCPV approach. The heat transport system, the electric and thermal performance, the manufacturing cost, and the resulting cost of energy in case of domestic water heating have been analyzed. The results show that the new approach has promising prospects

  15. Electromigration driven failures on miniature silver fuses at the Large Hadron Collider

    CERN Document Server

    Trikoupis, Nikolaos; Perez Fontenla, Ana Teresa

    2017-01-01

    Spurious faults were observed on the miniature silver fuses of electronic cards used for the cryogenics instrumentation in the LHC (Large Hadron Collider) accelerator at CERN. By applying analytical tools and techniques such as Scanning Electron Microscopy, spectrometry and Weibull reliability calculations and by the knowledge of operating temperatures and operational time of each unit, the origin of the problem has now been understood and can be attributed to electromigration. The selected fuse was operated at moderate temperature and load conditions and was considered as a “lifetime” component. However, it turned out to have a smaller than expected MTTF with failures following a Weibull distribution of $\\beta = 3.91$ and $\\eta = 2323$. The literature describes extensively the effects of electromigration, but there are only limited references referring to the impact of this phenomenon on miniature silver fuses for electronic circuits.

  16. Miniature Integrated-Optic Trace-Gas Sensors for Off-World Science Missions, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — As miniaturized satellite platforms such as CubeSat increase in capability, they will eventually be deployed to other planetary bodies (e.g., JPL INSPIRE). An...

  17. Spontaneous deregulation

    NARCIS (Netherlands)

    Edelman, Benjamin; Geradin, Damien

    Platform businesses such as Airbnb and Uber have risen to success partly by sidestepping laws and regulations that encumber their traditional competitors. Such rule flouting is what the authors call “spontaneous private deregulation,” and it’s happening in a growing number of industries. The authors

  18. Low-Power Receive-Electronics for a Miniature 3D Ultrasound Probe

    NARCIS (Netherlands)

    Yu, Z.

    2012-01-01

    This thesis describes the design of a front-end application-specific integrated circuit (ASIC), which will be put into the tip of a miniature ultrasound probe for 3D Trans-Esophageal Echocardiography (TEE). To enable 3D TEE, a matrix piezoelectric ultrasound transducer with more than 2000 elements

  19. A first step towards miniaturized HPLC systems in analytical routine laboratories

    NARCIS (Netherlands)

    Straten, van M.A.; Vermeer, E.A.; Claessens, H.A.

    1996-01-01

    This article shows that the first step towards the miniaturization of HPLC systems can be made without any, or only slight, modification to conventional equipment. Minor (less expensive) equipment modifications, particularly the use of micro-detector cells, allow the routine use of 3.2- and 2.1-mm

  20. A case of spontaneous ventriculocisternostomy

    International Nuclear Information System (INIS)

    Yamane, Kanji; Yoshimoto, Hisanori; Harada, Kiyoshi; Uozumi, Tohru; Kuwabara, Satoshi.

    1983-01-01

    The authors experienced a case of spontaneous ventriculocisternostomy diagnosed by CT scan with metrizamide and Conray. Patient was 23-year-old male who had been in good health until one month before admission, when he began to have headache and tinnitus. He noticed bilateral visual acuity was decreased about one week before admission and vomiting appeared two days before admission. He was admitted to our hospital because of bilateral papilledema and remarkable hydrocephalus diagnosed by CT scan. On admission, no abnormal neurological signs except for bilateral papilledema were noted. Immediately, right ventricular drainage was performed. Pressure of the ventricle was over 300mmH 2 O and CSF was clear. PVG and PEG disclosed an another cavity behind the third ventricle, which was communicated with the third ventricle, and occlusion of aqueduct of Sylvius. Metrizamide CT scan and Conray CT scan showed a communication between this cavity and quadrigeminal and supracerebellar cisterns. On these neuroradiological findings, the diagnosis of obstructive hydrocephalus due to benign aqueduct stenosis accompanied with spontaneous ventriculocisternostomy was obtained. Spontaneous ventriculocisternostomy was noticed to produce arrest of hydrocephalus, but with our case, spontaneous regression of such symptoms did not appeared. By surgical ventriculocisternostomy (method by Torkildsen, Dandy, or Scarff), arrest of hydrocephalus was seen in about 50 to 70 per cent, which was the same results as those of spontaneous ventriculocisternostomy. It is concluded that VP shunt or VA shunt is thought to be better treatment of obstructive hydrocephalus than the various kinds of surgical ventriculocisternostomy. (J.P.N.)

  1. Miniature Time of Flight Mass Spectrometer for Space and Extraterrestrial Applications, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The PI has developed a miniature time-of-flight mass spectrometer (TOF-MS), which can be op-timized for space and extraterrestrial applications, by using a...

  2. A miniature microbial fuel cell with conducting nanofibers-based 3D porous biofilm

    International Nuclear Information System (INIS)

    Jiang, Huawei; Dong, Liang; Halverson, Larry J

    2015-01-01

    Miniature microbial fuel cell (MFC) technology has received growing interest due to its potential applications in high-throughput screening of bacteria and mutants to elucidate mechanisms of electricity generation. This paper reports a novel miniature MFC with an improved output power density and short startup time, utilizing electrospun conducting poly(3,4-ethylenedioxythiophene) (PEDOT) nanofibers as a 3D porous anode within a 12 μl anolyte chamber. This device results in 423 μW cm −3 power density based on the volume of the anolyte chamber, using Shewanella oneidensis MR-1 as a model biocatalyst without any optimization of bacterial culture. The device also excels in a startup time of only 1hr. The high conductivity of the electrospun nanofibers makes them suitable for efficient electron transfer. The mean pore size of the conducting nanofibers is several micrometers, which is favorable for bacterial penetration and colonization of surfaces of the nanofibers. We demonstrate that S. oneidensis can fully colonize the interior region of this nanofibers-based porous anode. This work represents a new attempt to explore the use of electrospun PEDOT nanofibers as a 3D anode material for MFCs. The presented miniature MFC potentially will provide a high-sensitivity, high-throughput tool to screen suitable bacterial species and mutant strains for use in large-size MFCs. (paper)

  3. Disseminated Mycobacterium avium--intracellulare complex infection in a miniature schnauzer.

    Science.gov (United States)

    Miller, M A; Greene, C E; Brix, A E

    1995-01-01

    A two-year-old, spayed female, miniature schnauzer was evaluated for respiratory distress associated with a compressive cervical mass. Generalized mycobacterial infection was diagnosed from aspirates of several enlarged lymph nodes. Tissue specimens further identified Mycobacterium avium--intracellulare using polymerase chain reaction followed by nucleic acid hybridization. Treatment with enrofloxacin, clofazamine, rifampin, and interferon did not result in long-term success.

  4. Regeneration of cervical reserve cell-like cells from human induced pluripotent stem cells (iPSCs): A new approach to finding targets for cervical cancer stem cell treatment.

    Science.gov (United States)

    Sato, Masakazu; Kawana, Kei; Adachi, Katsuyuki; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Ogishima, Juri; Eguchi, Satoko; Yamashita, Aki; Tomio, Kensuke; Wada-Hiraike, Osamu; Oda, Katsutoshi; Nagamatsu, Takeshi; Osuga, Yutaka; Fujii, Tomoyuki

    2017-06-20

    Cervical reserve cells are epithelial progenitor cells that are pathologically evident as the origin of cervical cancer. Thus, investigating the characteristics of cervical reserve cells could yield insight into the features of cervical cancer stem cells (CSCs). In this study, we established a method for the regeneration of cervical reserve cell-like properties from human induced pluripotent stem cells (iPSCs) and named these cells induced reserve cell-like cells (iRCs). Approximately 70% of iRCs were positive for the reserve cell markers p63, CK5 and CK8. iRCs also expressed the SC junction markers CK7, AGR2, CD63, MMP7 and GDA. While iRCs expressed neither ERα nor ERβ, they expressed CA125. These data indicated that iRCs possessed characteristics of cervical epithelial progenitor cells. iRCs secreted higher levels of several inflammatory cytokines such as macrophage migration inhibitory factor (MIF), soluble intercellular adhesion molecule 1 (sICAM-1) and C-X-C motif ligand 10 (CXCL-10) compared with normal cervical epithelial cells. iRCs also expressed human leukocyte antigen-G (HLA-G), which is an important cell-surface antigen for immune tolerance and carcinogenesis. Together with the fact that cervical CSCs can originate from reserve cells, our data suggested that iRCs were potent immune modulators that might favor cervical cancer cell survival. In conclusion, by generating reserve cell-like properties from iPSCs, we provide a new approach that may yield new insight into cervical cancer stem cells and help find new oncogenic targets.

  5. Quantifying emissions from spontaneous combustion

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-09-01

    Spontaneous combustion can be a significant problem in the coal industry, not only due to the obvious safety hazard and the potential loss of valuable assets, but also with respect to the release of gaseous pollutants, especially CO2, from uncontrolled coal fires. This report reviews methodologies for measuring emissions from spontaneous combustion and discusses methods for quantifying, estimating and accounting for the purpose of preparing emission inventories.

  6. Guided-wave high-performance spectrometers for the MEOS miniature earth observation satellite

    Science.gov (United States)

    Kruzelecky, Roman V.; Wong, Brian; Zou, Jing; Jamroz, Wes; Sloan, James; Cloutis, Edward

    2017-11-01

    The MEOS Miniature Earth Observing Satellite is a low-cost mission being developed for the Canadian Space Agency with international collaborations that will innovatively combine remote correlated atmospheric/land-cover measurements with the corresponding atmospheric and ecosystem modelling in near real-time to obtain simultaneous variations in lower tropospheric GHG mixing ratios and the resulting responses of the surface ecosystems. MEOS will provide lower tropospheric CO2, CH4, CO, N2O, H2O and aerosol mixing ratios over natural sources and sinks using two kinds of synergistic observations; a forward limb measurement and a follow-on nadir measurement over the same geographical tangent point. The measurements will be accomplished using separate limb and nadir suites of innovative miniature line-imaging spectrometers and will be spatially coordinated such that the same air mass is observed in both views within a few minutes. The limb data will consist of 16-pixel vertical spectral line imaging to provide 1-km vertical resolution, while the corresponding nadir measurements will view sixteen 5 by 10 km2 ground pixels with a 160-km East-West swath width. To facilitate the mission accommodation on a low-cost microsat with a net payload mass under 22 kg, groundbreaking miniature guided-wave spectrometers with advanced optical filtering and coding technologies will be employed based on MPBC's patented IOSPEC technologies. The data synergy requirements for each view will be innovatively met using two complementary miniature line-imaging spectrometers to provide broad-band measurements from 1200 to 2450 nm at about 1.2 nm/pixel bandwidth using a multislit binary-coded MEMS-IOSPEC and simultaneous high-resolution multiple microchannels at 0.03 nm FWHM using the revolutionary FP-IOSPEC Fabry-Perot guided-wave spectrometer concept. The guided-wave spectrometer integration provides an order of magnitude reduction in the mass and volume relative to traditional bulk

  7. Miniaturized tools and devices for bioanalytical applications: an overview

    DEFF Research Database (Denmark)

    Chudy, M.; Grabowska, I.; Ciosek, P.

    2009-01-01

    This article presents an overview of various miniaturized devices and technologies developed by our group. Innovative, fast and cheap procedures for the fabrication of laboratory microsystems based on commercially available materials are reported and compared with well-established microfabricatio...... optic detectors, potentiometric sensors platforms, microreactors and capillary electrophoresis (CE) microchips as well as integrated microsystems e. g. double detection microanalytical systems, devices for studying enzymatic reactions and a microsystem for cell culture and lysis....

  8. A miniature rigid/flex salinity measurement device fabricated using printed circuit processing techniques

    International Nuclear Information System (INIS)

    Broadbent, H A; Ketterl, T P; Reid, C S

    2010-01-01

    The design, fabrication and initial performance of a single substrate, miniature, low-cost conductivity, temperature, depth (CTD) sensor board with interconnects are presented. In combination these sensors measure ocean salinity. The miniature CTD device board was designed and fabricated as the main component of a 50 mm × 25 mm × 25 mm animal-attached biologger. The board was fabricated using printed circuit processes and consists of two distinct regions on a continuous single liquid crystal polymer substrate: an 18 mm × 28 mm rigid multi-metal sensor section and a 72 mm long flexible interconnect section. The 95% confidence intervals for the conductivity, temperature and pressure sensors were demonstrated to be ±0.083 mS cm −1 , 0.01 °C, and ±0.135 dbar, respectively.

  9. Miniature reciprocating heat pumps and engines

    Science.gov (United States)

    Thiesen, Jack H. (Inventor); Willen, Gary S. (Inventor); Mohling, Robert A. (Inventor)

    2003-01-01

    The present invention discloses a miniature thermodynamic device that can be constructed using standard micro-fabrication techniques. The device can be used to provide cooling, generate power, compress gases, pump fluids and reduce pressure below ambient (operate as a vacuum pump). Embodiments of the invention relating to the production of a cooling effect and the generation of electrical power, change the thermodynamic state of the system by extracting energy from a pressurized fluid. Energy extraction is attained using an expansion process, which is as nearly isentropic as possible for the appropriately chosen fluid. An isentropic expansion occurs when a compressed gas does work to expand, and in the disclosed embodiments, the gas does work by overcoming either an electrostatic or a magnetic force.

  10. Miniature multichannel analyzer for process monitoring

    International Nuclear Information System (INIS)

    Halbig, J.K.; Klosterbuer, S.F.; Russo, P.A.; Sprinkle, J.K. Jr.; Stephens, M.M.; Wiig, L.G.; Ianakiev, K.D.

    1993-01-01

    A new, 4,000-channel analyzer has been developed for gamma-ray spectroscopy applications. A design philosophy of hardware and software building blocks has been combined with design goals of simplicity, compactness, portability, and reliability. The result is a miniature, modular multichannel analyzer (MMMCA), which offers solution to a variety of nondestructive assay (NDA) needs in many areas of general application, independent of computer platform or operating system. Detector-signal analog electronics, the bias supply, and batteries are included in the virtually pocket-size, low-power MMMCA unit. The MMMCA features digital setup and control, automated data reduction, and automated quality assurance. Areas of current NDA applications include on-line continuous (process) monitoring, process material holdup measurements, and field inspections

  11. Closed loop control of the induction heating process using miniature magnetic sensors

    Science.gov (United States)

    Bentley, Anthony E.; Kelley, John Bruce; Zutavern, Fred J.

    2003-05-20

    A method and system for providing real-time, closed-loop control of the induction hardening process. A miniature magnetic sensor located near the outer surface of the workpiece measures changes in the surface magnetic field caused by changes in the magnetic properties of the workpiece as it heats up during induction heating (or cools down during quenching). A passive miniature magnetic sensor detects a distinct magnetic spike that appears when the saturation field, B.sub.sat, of the workpiece has been exceeded. This distinct magnetic spike disappears when the workpiece's surface temperature exceeds its Curie temperature, due to the sudden decrease in its magnetic permeability. Alternatively, an active magnetic sensor can measure changes in the resonance response of the monitor coil when the excitation coil is linearly swept over 0-10 MHz, due to changes in the magnetic permeability and electrical resistivity of the workpiece as its temperature increases (or decreases).

  12. Development of a miniature Taylor-Couette extractor column for nuclear solvent extraction

    International Nuclear Information System (INIS)

    Shekhar Kumar; Sivakumar, D.; Bijendra Kumar; Kamachi Mudali, U.; Natarajan, R.

    2012-01-01

    Miniature annular centrifugal contactors are nearly perfect for shielded hot-cell applications during flowsheet evaluation but these contactors require complex maintenance of electrical drive-motors during radioactive experiments. To reduce the number of electrical drives in the shielded cell, an indigenous design of miniature Taylor Couette (TC) mixing based countercurrent differential extraction column has been developed. In this paper, results of mass transfer experiments for an indigenously developed TC column with 30% TBP/aqueous nitric acid solutions are reported. The developed device worked perfectly in counter-current differential mode and demonstrated equivalence to multiple-extraction stages while working with a single electrical drive. The developed TC unit demonstrated operation with a reduced efficiency without flooding even in absence of rotor rotation. This observation is a vital step towards designing of robust contactors, which do not flood during temporary power failure or failure of drive mechanism. (author)

  13. Increased Cortical Inhibition in Autism-Linked Neuroligin-3R451C Mice Is Due in Part to Loss of Endocannabinoid Signaling.

    Science.gov (United States)

    Speed, Haley E; Masiulis, Irene; Gibson, Jay R; Powell, Craig M

    2015-01-01

    A single, maternally inherited, X-linked point mutation leading to an arginine to cysteine substitution at amino acid 451 (R451C) of Neuroligin 3 (NLGN3R451C) is a likely cause of autism in two brothers. Knockin mice expressing the Nlgn3R451C mutation in place of wild-type Nlgn3 demonstrate increased inhibitory synaptic strength in somatosensory cortex, resulting in an excitatory/inhibitory (E/I) imbalance that is potentially relevant for autism-associated behavioral deficits characteristic of these mice. We have replicated the increase in evoked inhibitory postsynaptic currents (eIPSCs) onto layer II/III cortical pyramidal neurons. We also find that increased frequency of spontaneous mIPSCs in Nlgn3R451C mice occurs in the absence of action potential-driven transmission. This suggests the E/I imbalance is due to changes at the synapse level, as opposed to the network level. Next, we use paired whole-cell recordings in an attempt to identify specific interneuron subtypes affected by the Nlgn3R451C mutation. Curiously, we observe no change in the amplitude of cell-to-cell, unitary IPSCs (uIPSCs) from parvalbumin-positive (PV) or somatostatin-positive (SOM) interneurons onto pyramidal neurons. We also observe no change in the number or density of PV and SOM interneurons in LII/III of somatosensory cortex. This effectively rules out a role for these particular interneurons in the increased inhibitory synaptic transmission, pointing to perhaps alternative interneuron subtypes. Lastly, impaired endocannabinoid signaling has been implicated in hippocampal synaptic dysfunction in Nlgn3R451C mice, but has not been investigated at cortical synapses. We find that bath application of the CB1 antagonist, AM 251 in WT mice eliminates the Nlgn3R451C increase in eIPSC amplitude and mIPSC frequency, indicating that increased inhibitory transmission in mutant mice is due, at least in part, to a loss of endocannabinoid signaling through CB1 receptors likely acting at interneurons

  14. Increased Cortical Inhibition in Autism-Linked Neuroligin-3R451C Mice Is Due in Part to Loss of Endocannabinoid Signaling.

    Directory of Open Access Journals (Sweden)

    Haley E Speed

    Full Text Available A single, maternally inherited, X-linked point mutation leading to an arginine to cysteine substitution at amino acid 451 (R451C of Neuroligin 3 (NLGN3R451C is a likely cause of autism in two brothers. Knockin mice expressing the Nlgn3R451C mutation in place of wild-type Nlgn3 demonstrate increased inhibitory synaptic strength in somatosensory cortex, resulting in an excitatory/inhibitory (E/I imbalance that is potentially relevant for autism-associated behavioral deficits characteristic of these mice. We have replicated the increase in evoked inhibitory postsynaptic currents (eIPSCs onto layer II/III cortical pyramidal neurons. We also find that increased frequency of spontaneous mIPSCs in Nlgn3R451C mice occurs in the absence of action potential-driven transmission. This suggests the E/I imbalance is due to changes at the synapse level, as opposed to the network level. Next, we use paired whole-cell recordings in an attempt to identify specific interneuron subtypes affected by the Nlgn3R451C mutation. Curiously, we observe no change in the amplitude of cell-to-cell, unitary IPSCs (uIPSCs from parvalbumin-positive (PV or somatostatin-positive (SOM interneurons onto pyramidal neurons. We also observe no change in the number or density of PV and SOM interneurons in LII/III of somatosensory cortex. This effectively rules out a role for these particular interneurons in the increased inhibitory synaptic transmission, pointing to perhaps alternative interneuron subtypes. Lastly, impaired endocannabinoid signaling has been implicated in hippocampal synaptic dysfunction in Nlgn3R451C mice, but has not been investigated at cortical synapses. We find that bath application of the CB1 antagonist, AM 251 in WT mice eliminates the Nlgn3R451C increase in eIPSC amplitude and mIPSC frequency, indicating that increased inhibitory transmission in mutant mice is due, at least in part, to a loss of endocannabinoid signaling through CB1 receptors likely acting at

  15. Applications of Silicon-on-Insulator Photonic Crystal Structures in Miniature Spectrometer Designs

    Science.gov (United States)

    Gao, Boshen

    Optical spectroscopy is one of the most important fundamental scientific techniques. It has been widely adopted in physics, chemistry, biology, medicine and many other research fields. However, the size and weight of a spectrometer as well as the difficulty to align and maintain it have long limited spectroscopy to be a laboratory-only procedure. With the recent advancement in semiconductor electronics and photonics, miniaturized spectrometers have been introduced to complete many tasks in daily life where mobility and portability are necessary. This thesis focuses on the study of several photonic crystal (PC) nano-structures potentially suitable for miniaturized on-chip spectrometer designs. Chapter 1 briefly introduces the concept of PCs and their band structures. By analyzing the band structure, the origin of the superprism effect is explained. Defect-based PC nano-cavities are also discussed, as well as a type of coupled cavity waveguides (CCW) composed of PC nano-cavities. Chapter 2 is devoted to the optimization of a flat-band superprism structure for spectroscopy application using numerical simulations. Chapter 3 reports a fabricated broad-band superprism and the experimental characterization of its wavelength resolving performance. In chapter 4, the idea of composing a miniature spectrometer based on a single tunable PC nano-cavity is proposed. The rest of this chapter discusses the experimental study of this design. Chapter 5 examines the slow-light performance of a CCW and discusses its potential application in slow-light interferometry. Chapter 6 serves as a conclusion of this thesis and proposes directions for possible future work to follow up.

  16. Specific fetometric formulas of ICC and BP for calculating the parturition date in the miniature breeds of canine.

    Science.gov (United States)

    Socha, P; Janowski, T

    2018-04-01

    The aim of this study was to derive the growth curves of the inner chorionic cavity and the biparietal distance in miniature dog breeds by ultrasonographic fetometry and present new specific formulas for prediction of parturition date. In this study, foetal biometry parameters were obtained using serial ultrasonographic examinations in 24 pregnant bitches of six different miniature breeds (≤5 kg). The mating time was unknown. Overall, 25 inner chorionic cavity diameter (ICC) and 22 biparietal diameter (BP) measurements were taken. The relationship between ICC or BP growth and days to parturition was analysed by linear regression. The results showed a significant relationship between days before delivery and ICC or BP. The equations derived from the growth curves can be used in practical prediction of parturition date in miniature dog breeds. © 2018 Blackwell Verlag GmbH.

  17. Miniaturized heat flux sensor for high enthalpy plasma flow characterization

    International Nuclear Information System (INIS)

    Gardarein, Jean-Laurent; Battaglia, Jean-Luc; Lohlec, Stefan; Jullien, Pierre; Van Ootegemd, Bruno; Couzie, Jacques; Lasserre, Jean-Pierre

    2013-01-01

    An improved miniaturized heat flux sensor is presented aiming at measuring extreme heat fluxes of plasma wind tunnel flows. The sensor concept is based on an in-depth thermocouple measurement with a miniaturized design and an advanced calibration approach. Moreover, a better spatial estimation of the heat flux profile along the flow cross section is realized with this improved small sensor design. Based on the linearity assumption, the heat flux is determined using the impulse response of the sensor relating the heat flux to the temperature of the embedded thermocouple. The non-integer system identification (NISI) procedure is applied that allows a calculation of the impulse response from transient calibration measurements with a known heat flux of a laser source. The results show that the new sensor leads to radially highly resolved heat flux measurement for a flow with only a few centimetres in diameter, the so far not understood non-symmetric heat flux profiles do not occur with the new sensor design. It is shown that this former effect is not a physical effect of the flow, but a drawback of the classical sensor design. (authors)

  18. Miniature mechanical transfer optical coupler

    Science.gov (United States)

    Abel, Philip [Overland Park, KS; Watterson, Carl [Kansas City, MO

    2011-02-15

    A miniature mechanical transfer (MT) optical coupler ("MMTOC") for optically connecting a first plurality of optical fibers with at least one other plurality of optical fibers. The MMTOC may comprise a beam splitting element, a plurality of collimating lenses, and a plurality of alignment elements. The MMTOC may optically couple a first plurality of fibers disposed in a plurality of ferrules of a first MT connector with a second plurality of fibers disposed in a plurality of ferrules of a second MT connector and a third plurality of fibers disposed in a plurality of ferrules of a third MT connector. The beam splitting element may allow a portion of each beam of light from the first plurality of fibers to pass through to the second plurality of fibers and simultaneously reflect another portion of each beam of light from the first plurality of fibers to the third plurality of fibers.

  19. Miniature neutron-alpha activation spectrometer

    International Nuclear Information System (INIS)

    Rhodes, Edgar; Goldsten, John; Holloway, James Paul; He, Zhong

    2002-01-01

    We are developing a miniature neutron-alpha activation spectrometer for in-situ analysis of chem-bio samples, including rocks, fines, ices, and drill cores, suitable for a lander or Rover platform for Mars or outer-planet missions. In the neutron-activation mode, penetrating analysis will be performed of the whole sample using a γ spectrometer and in the α-activation mode, the sample surface will be analyzed using Rutherford-backscatter and x-ray spectrometers. Novel in our approach is the development of a switchable radioactive neutron source and a small high-resolution γ detector. The detectors and electronics will benefit from remote unattended operation capabilities resulting from our NEAR XGRS heritage and recent development of a Ge γ detector for MESSENGER. Much of the technology used in this instrument can be adapted to portable or unattended terrestrial applications for detection of explosives, chemical toxins, nuclear weapons, and contraband

  20. Spontaneous calf haematoma: case report.

    Science.gov (United States)

    Zubaidah, N H; Liew, N C

    2014-02-01

    Spontaneous calf haematoma is a rare condition and few case reports have been published in the English literature. Common conditions like deep vein thrombosis and traumatic gastrocnemius muscle tear need to be considered when a patient presents with unilateral calf swelling and tenderness. Ultrasound and Magnetic Resonance Imaging are essential for confirmation of diagnosis. The purpose of this paper is to report on a rare case of spontaneous calf hematoma and its diagnosis and management.