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Sample records for spontaneous miniature ipscs

  1. Miniature IPSCs in hippocampal granule cells are triggered by voltage-gated Ca2+ channels via microdomain coupling.

    Science.gov (United States)

    Goswami, Sarit Pati; Bucurenciu, Iancu; Jonas, Peter

    2012-10-10

    The coupling between presynaptic Ca(2+) channels and Ca(2+) sensors of exocytosis is a key determinant of synaptic transmission. Evoked release from parvalbumin (PV)-expressing interneurons is triggered by nanodomain coupling of P/Q-type Ca(2+) channels, whereas release from cholecystokinin (CCK)-containing interneurons is generated by microdomain coupling of N-type channels. Nanodomain coupling has several functional advantages, including speed and efficacy of transmission. One potential disadvantage is that stochastic opening of presynaptic Ca(2+) channels may trigger spontaneous transmitter release. We addressed this possibility in rat hippocampal granule cells, which receive converging inputs from different inhibitory sources. Both reduction of extracellular Ca(2+) concentration and the unselective Ca(2+) channel blocker Cd(2+) reduced the frequency of miniature IPSCs (mIPSCs) in granule cells by ∼50%, suggesting that the opening of presynaptic Ca(2+) channels contributes to spontaneous release. Application of the selective P/Q-type Ca(2+) channel blocker ω-agatoxin IVa had no detectable effects, whereas both the N-type blocker ω-conotoxin GVIa and the L-type blocker nimodipine reduced mIPSC frequency. Furthermore, both the fast Ca(2+) chelator BAPTA-AM and the slow chelator EGTA-AM reduced the mIPSC frequency, suggesting that Ca(2+)-dependent spontaneous release is triggered by microdomain rather than nanodomain coupling. The CB(1) receptor agonist WIN 55212-2 also decreased spontaneous release; this effect was occluded by prior application of ω-conotoxin GVIa, suggesting that a major fraction of Ca(2+)-dependent spontaneous release was generated at the terminals of CCK-expressing interneurons. Tonic inhibition generated by spontaneous opening of presynaptic N- and L-type Ca(2+) channels may be important for hippocampal information processing.

  2. Spontaneous ATM Gene Reversion in A-T iPSC to Produce an Isogenic Cell Line

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    Lucy Lin

    2015-12-01

    Full Text Available A spontaneously reverted iPSC line was identified from an A-T subject with heterozygous ATM truncation mutations. The reverted iPSC line expressed ATM protein and was capable of radiation-induced phosphorylation of CHK2 and H2A.X. Genome-wide SNP analysis confirmed a match to source T cells and also to a distinct, non-reverted iPSC line from the same subject. Rearranged T cell receptor sequences predict that the iPSC culture originated as several independently reprogrammed cells that resolved into a single major clone, suggesting that gene correction likely occurred early in the reprogramming process. Gene expression analysis comparing ATM−/− iPSC lines to unrelated ATM+/− cells identifies a large number of differences, but comparing only the isogenic pair of A-T iPSC lines reveals that the primary pathway affected by loss of ATM is a diminished expression of p53-related mRNAs. Gene reversion in culture, although likely a rare event, provided a novel, reverted cell line for studying ATM function.

  3. Changes of spontaneous miniature excitatory postsynaptic currents in rat hippocampal pyramidal cells induced by aniracetam.

    Science.gov (United States)

    Ghamari-Langroudi, M; Glavinovíc, M I

    1998-01-01

    Spontaneous miniature excitatory postsynaptic currents (mEPSCs) in rat hippocampal pyramidal neurones in slices (CA1 region) were recorded at 35-37 degrees C using the whole-cell patch-clamp technique before and after addition of aniracetam (1 mM) to determine how a partial blockade of desensitization alters the relationship between the amplitude (A) and kinetics of mEPSCs, and to evaluate the factors that determine their variability. The rise time (taur) and the time constant of decay of mEPSCs (taud) are essentially amplitude independent in control conditions, but become clearly amplitude dependent in the presence of aniracetam. The slopes of the best fitting lines to taud:A and taur:A data pairs were (+/- SD; ms/pA; n = 5): (1) (control) 0.07 +/- 0.02 and 0.008 +/- 0.003; (2) (aniracetam) 0.40 +/- 0.19 and 0.22 +/- 0.22. The amplitude-dependent prolongation of taud is explained by the concentration dependence of two related processes, the buffering of glutamate molecules by AMPA receptor channels, and the occupancy of the double-bound activatable states. A slower deactivation makes an amplitude-independent contribution. Desensitization reduces the amplitude dependence of taud by minimizing repeated openings of alpha-amino-3-hydroxy-methyl-isoxazole (AMPA) receptor channels. A greater amplitude dependence of taur probably involves both pre- and postsynaptic factors. The variability of A and taud values did not change significantly, but the factors underlying the variability of taud values were much affected. The greater amplitude dependence and the greater scatter about the best fitting lines to taud:A data pairs are approximately balanced by the greater mean values. The greater scatter of taud about the best fitting lines probably occurs because the saturation of AMPA receptors is not the same at different synapses with different numbers of AMPA receptors.

  4. iPSC Core

    Data.gov (United States)

    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...

  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. Generation of an iPSC line from a patient with tyrosine hydroxylase (TH) deficiency: TH-1 iPSC.

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    Jung-Klawitter, Sabine; Blau, Nenad; Sebe, Attila; Ebersold, Juliane; Göhring, Gudrun; Opladen, Thomas

    2016-11-01

    Fibroblasts from a male patient with compound heterozygous variants in the tyrosine hydroxylase gene (TH; OMIM: 191290; c.[385-C>T]; [692-G>C]/p.[R129*]; [R231P]), the rate-limiting enzyme for dopamine synthesis, were reprogrammed to iPSCs using episomal reprogramming delivering the reprogramming factors Oct3/4, Sox2, L-Myc, Lin28, Klf4 and p53 shRNA Okita et al. (2011). Pluripotency of TH-1 iPSC was verified by immunohistochemistry and RT-PCR analysis. Cells exhibited a normal karyotype and differentiated spontaneously into the 3 germ layers in vitro. TH-1 iPSC represents the first model system to study the pathomechanism of this rare metabolic disease and provides a useful tool for drug testing. Copyright © 2016 Michael Boutros, German Cancer Research Center, Heidelberg, Germany. Published by Elsevier B.V. All rights reserved.

  7. Immunoglobulins from amyotrophic lateral sclerosis patients enhance the frequency of glycine-mediated spontaneous inhibitory postsynaptic currents in rat hypoglossal motoneurons

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    Anđus P.R.

    2007-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a devastating, still incurable neurological disorder affecting upper and lower motoneurons. Passive transfer of the disease occurs when immunoglobulins from ALS patients are injected into experimental animals. It is suggested that ALS IgGs cause excitotoxicity by acting on voltage-gated Ca2+ channels. We reported previously that ALS IgGs increase spontaneous release of glutamate in hippocampal neurons. Since these cells are not normally affected in ALS, we here studied the effect of ALS IgGs on hypoglossal motoneurons in rat brain-stem slices. The frequency of spontaneous glycine-mediated inhibitory postsynaptic currents (sIPSCs was augmented, but not that of miniature ones (mIPSCs, thus pointing to an indirect effect on release.

  8. 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.

  9. Generation of iPSCs as a Pooled Culture Using Magnetic Activated Cell Sorting of Newly Reprogrammed Cells.

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    Wenli Yang

    Full Text Available Although significant advancement has been made in the induced pluripotent stem cell (iPSC field, current methods for iPSC derivation are labor intensive and costly. These methods involve manual selection, expansion, and characterization of multiple clones for each reprogrammed cell sample and therefore significantly hampers the feasibility of studies where a large number of iPSCs need to be derived. To develop higher throughput iPSC reprogramming methods, we generated iPSCs as a pooled culture using rigorous cell surface pluripotent marker selection with TRA-1-60 or SSEA4 antibodies followed by Magnetic Activated Cell Sorting (MACS. We observed that pool-selected cells are similar or identical to clonally derived iPSC lines from the same donor by all criteria examined, including stable expression of endogenous pluripotency genes, normal karyotype, loss of exogenous reprogramming factors, and in vitro spontaneous and lineage directed differentiation potential. This strategy can be generalized for iPSC generation using both integrating and non-integrating reprogramming methods. Our studies provide an attractive alternative to clonal derivation of iPSCs using rigorously selected cell pools and is amenable to automation.

  10. Establishment of induced pluripotent stem cell (iPSC line from a 57-year old patient with sporadic Alzheimer's disease

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    Anna Ochalek

    2016-07-01

    Full Text Available Peripheral blood mononuclear cells (PBMCs were collected from a clinically characterised 57-year old woman with sporadic Alzheimer's disease. 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.

  11. Small molecules facilitate rapid and synchronous iPSC generation

    OpenAIRE

    Bar-Nur, Ori; Brumbaugh, Justin; Verheul, Cassandra; Apostolou, Effie; Pruteanu-Malinici, Iulian; Walsh, Ryan M.; Ramaswamy, Sridhar; Hochedlinger, Konrad

    2014-01-01

    The reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) upon overexpression of OCT4, KLF4, SOX2, and c-MYC (OKSM) provides a powerful system to interrogate basic mechanisms of cell fate change. However, iPSC formation with standard methods is protracted and inefficient, resulting in heterogeneous cell populations. Here we show that exposure of OKSM-expressing cells to both ascorbic acid and a GSK3-beta inhibitor (termed ?AGi?) facilitates more synchronous and rapid iPSC...

  12. 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.

  13. Deficits in human trisomy 21 iPSCs and neurons.

    Science.gov (United States)

    Weick, Jason P; Held, Dustie L; Bonadurer, George F; Doers, Matthew E; Liu, Yan; Maguire, Chelsie; Clark, Aaron; Knackert, Joshua A; Molinarolo, Katharine; Musser, Michael; Yao, Lin; Yin, Yingnan; Lu, Jianfeng; Zhang, Xiaoqing; Zhang, Su-Chun; Bhattacharyya, Anita

    2013-06-11

    Down syndrome (trisomy 21) is the most common genetic cause of intellectual disability, but the precise molecular mechanisms underlying impaired cognition remain unclear. Elucidation of these mechanisms has been hindered by the lack of a model system that contains full trisomy of chromosome 21 (Ts21) in a human genome that enables normal gene regulation. To overcome this limitation, we created Ts21-induced pluripotent stem cells (iPSCs) from two sets of Ts21 human fibroblasts. One of the fibroblast lines had low level mosaicism for Ts21 and yielded Ts21 iPSCs and an isogenic control that is disomic for human chromosome 21 (HSA21). Differentiation of all Ts21 iPSCs yielded similar numbers of neurons expressing markers characteristic of dorsal forebrain neurons that were functionally similar to controls. Expression profiling of Ts21 iPSCs and their neuronal derivatives revealed changes in HSA21 genes consistent with the presence of 50% more genetic material as well as changes in non-HSA21 genes that suggested compensatory responses to oxidative stress. Ts21 neurons displayed reduced synaptic activity, affecting excitatory and inhibitory synapses equally. Thus, Ts21 iPSCs and neurons display unique developmental defects that are consistent with cognitive deficits in individuals with Down syndrome and may enable discovery of the underlying causes of and treatments for this disorder.

  14. Mechanism of Induction: Induced Pluripotent Stem Cells (iPSCs).

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    Singh, Vimal Kishor; Kumar, Neeraj; Kalsan, Manisha; Saini, Abhishek; Chandra, Ramesh

    2015-01-01

    Induced Pluripotent Stem Cells (iPSCs) are self renewable and can differentiate to different types of adult cells, which has shown great promises in the field of regenerative medicine. iPSCs are reprogrammed from human somatic cells through ectopic expression of various transcription factors viz. Oct4, Sox2, Klf4, and c-Myc (OSKM). This novel technology enables derivation of patient specific cells, which possess a potential cure for many diseases. During the last decade, significant progresses have been achieved in enhancing the reprogramming efficiency, safety of iPSCs derivation, development of different delivery techniques by various research groups. Nevertheless, it is important to resolve and define the mechanism underlying the pluripotent stem cells. Major bottleneck which arises during iPSCs generation is the availability of source material (cells/tissues), difficulty to deliver transcription factors with no aberrant genetic modifications and limited reprogramming efficiency. Reprogramming may be achieved by employing different cocktails with number of different transcription factors, application of miRNA and some small molecules such as (Valproic acid, CHiR99021, Sodium butyrate, Vitamin C, Parnate etc). Similarly, various starting source materials have been demonstrated for iPSC based therapies including fibroblasts, cord blood, peripheral blood, keritinocytes, urine, etc., with their specific uses and limitations. Moreover, with the advent of many new reprogramming techniques, various direct delivery methods have been introduced such as using synthetic mRNA expressing pluripotent gene network has been shown to be an appropriate technique to deliver transcription factors and a dozen of small molecules which can replace transcription factors or enhance reprogramming efficiency. This article addresses the iPSCs technology mechanisms, progresses and current perspectives in the field.

  15. Systematic Identification of Barriers to Human iPSC Generation

    OpenAIRE

    Qin, Han; Diaz, Aaron; Blouin, Laure; Lebbink, Robert Jan; Patena, Weronika; Tanbun, Priscilia; LeProust, Emily M.; McManus, Michael T.; Song, Jun S.; Ramalho-Santos, Miguel

    2014-01-01

    Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) holds enormous promise for regenerative medicine, but the underlying mechanisms remain poorly understood. We report a systematic dissection of human cellular reprogramming by combining a genome-wide RNAi screen, innovative computational methods, extensive single-hit validation and mechanistic dissection of relevant pathways and networks. We identify novel reprogramming barriers, including genes involved in transcription,...

  16. 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...

  17. Advancing induced pluripotent stem cell (iPSC) technology by assessing genetic instability and immune response

    OpenAIRE

    Requena Osete, Jordi

    2017-01-01

    [eng] Induced pluripotent stem cells (iPSC) can be made from adult somatic cells by reprogramming them with Oct4, Sox2, Klf4 and c-Myc. IPSC have given rise to a new technology to study and treat human disease (Takahashi et al., 2007). However, before iPSC clinical application, we need to step back and address two main challenges: (i) Genetic stability of iPSC. (ii) Immune response of iPSC-derived cells. To address these key issues, the overall mission of this PhD thesis is to adva...

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

    Science.gov (United States)

    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

  19. 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...... capacity. Here we review the epigenetic changes with a focus on histone modification (methylation and acetylation) and DNA modification (methylation) during iPSC induction. We look at changes in specific epigenetic signatures, aberrations and epigenetic memory during reprogramming and small molecules...... influencing the epigenetic reprogramming of somatic cells. Finally, we discuss how to improve iPSC generation and pluripotency through epigenetic manipulations....

  20. Reflections on Miniature Golf.

    Science.gov (United States)

    Powell, Nancy Norem; And Others

    1994-01-01

    Describes a transformational geometry project in which groups of students explore symmetry, reflections, translations, rotations, and dilations to design and create one hole of miniature golf large enough to play on. Includes unit plan for transformational geometry. (MKR)

  1. Miniature Release Mechanism Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The objective is to design, build and functionally test a miniature release mechanism for CubeSats and other small satellites. The WFF 6U satellite structure will be...

  2. Miniaturization 2007 Issue. Editorial

    Czech Academy of Sciences Publication Activity Database

    Foret, František; Kutter, J. P.

    2007-01-01

    Roč. 28, č. 24 (2007), s. 4509 ISSN 0173-0835 Institutional research plan: CEZ:AV0Z40310501 Keywords : miniaturization * special issue * editorial Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.609, year: 2007

  3. Miniature oxygen resuscitator

    Science.gov (United States)

    Johnson, G.; Teegen, J. T.; Waddell, H.

    1969-01-01

    Miniature, portable resuscitation system is used during evacuation of patients to medical facilities. A carrying case contains a modified resuscitator head, cylinder of oxygen, two-stage oxygen regulator, low pressure tube, and a mask for mouth and nose.

  4. The cholinergic agonist carbachol increases the frequency of spontaneous GABAergic synaptic currents in dorsal raphe serotonergic neurons in the mouse.

    Science.gov (United States)

    Yang, C; Brown, R E

    2014-01-31

    Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons play an important role in feeding, mood control and stress responses. One important feature of their activity across the sleep-wake cycle is their reduced firing during rapid-eye-movement (REM) sleep which stands in stark contrast to the wake/REM-on discharge pattern of brainstem cholinergic neurons. A prominent model of REM sleep control posits a reciprocal interaction between these cell groups. 5-HT inhibits cholinergic neurons, and activation of nicotinic receptors can excite DRN 5-HT neurons but the cholinergic effect on inhibitory inputs is incompletely understood. Here, in vitro, in DRN brain slices prepared from GAD67-GFP knock-in mice, a brief (3 min) bath application of carbachol (50 μM) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in GFP-negative, putative 5-HT neurons but did not affect miniature (tetrodotoxin-insensitive) IPSCs. Carbachol had no direct postsynaptic effect. Thus, carbachol likely increases the activity of local GABAergic neurons which synapse on 5-HT neurons. Removal of dorsal regions of the slice including the ventrolateral periaqueductal gray (vlPAG) region where GABAergic neurons projecting to the DRN have been identified, abolished the effect of carbachol on sIPSCs whereas the removal of ventral regions containing the oral region of the pontine reticular nucleus (PnO) did not. In addition, carbachol directly excited GFP-positive, GABAergic vlPAG neurons. Antagonism of both muscarinic and nicotinic receptors completely abolished the effects of carbachol. We suggest cholinergic neurons inhibit DRN 5-HT neurons when acetylcholine levels are lower i.e. during quiet wakefulness and the beginning of REM sleep periods, in part via excitation of muscarinic and nicotinic receptors located on local vlPAG and DRN GABAergic neurons. Higher firing rates or burst firing of cholinergic neurons associated with attentive wakefulness or phasic REM sleep periods

  5. 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

  6. 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....

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

    Science.gov (United States)

    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.

  8. The Application of Human iPSCs in Neurological Diseases: From Bench to Bedside

    Directory of Open Access Journals (Sweden)

    Nina Xie

    2016-01-01

    Full Text Available In principle, induced pluripotent stem cells (iPSCs are generated from somatic cells by reprogramming and gaining the capacity to self-renew indefinitely as well as the ability to differentiate into cells of different lineages. Human iPSCs have absolute advantages over human embryonic stem cells (ESCs and animal models in disease modeling, drug screening, and cell replacement therapy. Since Takahashi and Yamanaka first described in 2007 that iPSCs can be generated from human adult somatic cells by retroviral transduction of the four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc, disease specific iPSC lines have sprung up worldwide like bamboo shoots after a spring rain, making iPSC one of the hottest and fastest moving topics in modern science. The craze for iPSCs has spread throughout main branches of clinical medicine, covering neurology, hematology, cardiology, endocrinology, hepatology, ophthalmology, and so on. Here in this paper, we will focus on the clinical application of human iPSCs in disease modeling, drug screening, and cell replacement therapy for neurological diseases.

  9. Miniaturization in Biocatalysis

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    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.

  10. Miniaturization in Biocatalysis

    Science.gov (United States)

    Fernandes, Pedro

    2010-01-01

    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. PMID:20479988

  11. 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.

  12. 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...

  13. Miniaturized photoacoustic spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Okandan, Murat; Robinson, Alex; Nielson, Gregory N.; Resnick, Paul J.

    2016-08-09

    A low-power miniaturized photoacoustic sensor uses an optical microphone made by semiconductor fabrication techniques, and optionally allows for all-optical communication to and from the sensor. This allows integration of the photoacoustic sensor into systems with special requirements, such as those that would be reactive in an electrical discharge condition. The photoacoustic sensor can also be operated in various other modes with wide application flexibility.

  14. 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.

  15. 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 ...

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

    Science.gov (United States)

    Brix, Jacob; Zhou, Yan; Luo, Yonglun

    2015-12-20

    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 reprogramming, pluripotency, and differentiation capacity. Here, we review the epigenetic changes with a focus on histone modification (methylation and acetylation) and DNA modification (methylation) during iPSC induction. We look at changes in specific epigenetic signatures, aberrations and epigenetic memory during reprogramming and small molecules influencing the epigenetic reprogramming of somatic cells. Finally, we discuss how to improve iPSC generation and pluripotency through epigenetic manipulations. Copyright © 2015 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Miniature Laser Magnetometer

    Science.gov (United States)

    Slocum, Robert; Brown, Andy

    2011-01-01

    A conceptual design has been developed for a miniature laser magnetometer (MLM) that will measure the scalar magnitude and vector components of near-Earth magnetic fields. The MLM incorporates a number of technical innovations to achieve high-accuracy and high-resolution performance while significantly reducing the size of the laser-pumped helium magnetometer for use on small satellites and unmanned aerial vehicles (UAVs). and electronics sections that has the capability of measuring both the scalar magnetic field magnitude and the vector magnetic field components. Further more, the high-accuracy scalar measurements are used to calibrate and correct the vector component measurements in order to achieve superior vector accuracy and stability. The correction algorithm applied to the vector components for calibration and the same cell for vector and scalar measurements are major innovations. The separate sensor and electronics section of the MLM instrument allow the sensor to be installed on a boom or otherwise located away from electronics and other noisy magnetic components. The MLM s miniaturization will be accomplished through the use of advanced miniaturized components and packaging methods for the MLM sensor and electronics. The MLM conceptual design includes three key innovations. The first is a new non-magnetic laser package that will allow the placement of the laser pump source near the helium cell sensing elements. The second innovation is the design of compact, nested, triaxial Braunbek coils used in the vector measurements that reduce the coil size by a factor of two compared to existing Helmholtz coils with similar field-generation performance. The third innovation is a compact sensor design that reduces the sensor volume by a factor of eight compared to MLM s predecessor.

  20. 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

  1. Proteinuria and lipoprotein lipase activity in Miniature schnauzer dogs with and without hypertriglyceridemia

    OpenAIRE

    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.

    2016-01-01

    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 shnauzers. The aims of this study were to determine ...

  2. Spontaneous pneumothorax

    Directory of Open Access Journals (Sweden)

    Davari R

    1996-07-01

    Full Text Available A case with bilateral spontaneous pneumothorax was presented. Etiology, mechanism, and treatment were discussed on the review of literature. Spontaneous Pneumothorax is a clinical entity resulting from a sudden non traumatic rupture of the lung. Biach reported in 1880 that 78% of 916 patients with spontaneous pneumothorax had tuberculosis. Kjergaard emphasized 1932 the primary importance of subpleural bleb disease. Currently the clinical spectrum of spontaneous pneumothorax seems to have entered a third era with the recognition of the interstitial lung disease and AIDS as a significant etiology. Standard treatment is including: observation, thoracocentesis, tube thoracostomy. Chemical pleurodesis, bullectomy or wedge resection of lung with pleural abrasion and occasionally pleurectomy. Little information has been reported regarding the efficacy of such treatment in spontaneous pneumothorax secondary to non bleb disease

  3. Manipulation of KLF4 Expression Generates iPSCs Paused at Successive Stages of Reprogramming

    Directory of Open Access Journals (Sweden)

    Ken Nishimura

    2014-11-01

    Full Text Available The detailed mechanism of reprogramming somatic cells into induced pluripotent stem cells (iPSCs remains largely unknown. Partially reprogrammed iPSCs are informative and useful for understanding the mechanism of reprogramming but remain technically difficult to generate in a predictable and reproducible manner. Using replication-defective and persistent Sendai virus (SeVdp vectors, we analyzed the effect of decreasing the expression levels of OCT4, SOX2, KLF4, and c-MYC and found that low KLF4 expression reproducibly gives rise to a homogeneous population of partially reprogrammed iPSCs. Upregulation of KLF4 allows these cells to resume reprogramming, indicating that they are paused iPSCs that remain on the path toward pluripotency. Paused iPSCs with different KLF4 expression levels remain at distinct intermediate stages of reprogramming. This SeVdp-based stage-specific reprogramming system (3S reprogramming system is applicable for both mouse and human somatic cells and will facilitate the mechanistic analysis of reprogramming.

  4. Recent advances in iPSC technologies involving cardiovascular and neurodegenerative disease modeling.

    Science.gov (United States)

    Csöbönyeiová, Mária; Danišovič, Ľuboš; Polák, Štefan

    2016-01-01

    Cardiovascular and neurodegenerative diseases are the most common health threats in developed countries. Limited cell derivation and cell number in cardiac tissue makes it difficult to study the cardiovascular disease using the existing cardiac cell model. Regarding the neurodegenerative disorders, the most potential sources of cell therapeutics such as fetal-derived primary neurons and human embryonic stem cells (ESCs) are associated with ethical or technical limitations. The successful derivation of human-induced pluripotent stem cells (iPSCs) by de-differentiation of somatic cells offers significant potential to overcome hurdles in the field of the replacement therapy. Human iPSCs are functionally similar to human embryonic stem cells, and can be derived autologously without the ethical challenges associated with human ESCs. The iPSCs can, in turn, be differentiated into all cell types including neurons, cardiac cells, blood and liver cells, etc. Recently, target tissues derived from human iPSCs such as cardiomyocytes (CMs) or neurons have been used for new disease modeling and regenerative medicine therapies. Diseases models could be advantageous in the development of personalized medicine of various pathological conditions. This paper reviews efforts aimed at both the practical development of iPSCs, differentiation to neural/cardiac lineages, and the further use of these iPSCs-derived cells for disease modeling, as well as drug toxicity testing.

  5. 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

  6. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Orqueda, Andrés Javier; Giménez, Carla Alejandra; Pereyra-Bonnet, Federico

    2016-01-01

    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. 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.

  10. 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

  11. 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...

  12. Central Hypothyroidism in Miniature Schnauzers

    OpenAIRE

    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 possible role of the thyroid-stimulating hormone (TSH)-releasing hormone receptor (TRHR) gene and the TSH beta (TSHB) gene was investigated. Animals: Miniature Schnauzers with proven central...

  13. Miniature Chemical Sensor

    Energy Technology Data Exchange (ETDEWEB)

    Andrew C. R. Pipino

    2004-12-13

    A new chemical detection technology has been realized that addresses DOE environmental management needs. The new technology is based on a variant of the sensitive optical absorption technique, cavity ring-down spectroscopy (CRDS). Termed evanescent-wave cavity ring-down spectroscopy (EW-CRDS), the technology employs a miniature solid-state optical resonator having an extremely high Q-factor as the sensing element, where the high-Q is achieved by using ultra-low-attenuation optical materials, ultra-smooth surfaces, and ultra-high reflectivity coatings, as well as low-diffraction-loss designs. At least one total-internal reflection (TIR) mirror is integral to the resonator permitting the concomitant evanescent wave to probe the ambient environment. Several prototypes have been designed, fabricated, characterized, and applied to chemical detection. Moreover, extensions of the sensing concept have been explored to enhance selectivity, sensitivity, and range of application. Operating primarily in the visible and near IR regions, the technology inherently enables remote detection by optical fiber. Producing 11 archival publications, 5 patents, 19 invited talks, 4 conference proceedings, a CRADA, and a patent-license agreement, the project has realized a new chemical detection technology providing >100 times more sensitivity than comparable technologies, while also providing practical advantages.

  14. Noise in miniature microphones.

    Science.gov (United States)

    Thompson, Stephen C; LoPresti, Janice L; Ring, Eugene M; Nepomuceno, Henry G; Beard, John J; Ballad, William J; Carlson, Elmer V

    2002-02-01

    The internal noise spectrum in miniature electret microphones of the type used in the manufacture of hearing aids is measured. An analogous circuit model of the microphone is empirically fit to the measured data and used to determine the important sources of noise within the microphone. The dominant noise source is found to depend on the frequency. Below 40 Hz and above 9 kHz, the dominant source is electrical noise from the amplifier circuit needed to buffer the electrical signal from the microphone diaphragm. Between approximately 40 Hz and 1 kHz, the dominant source is thermal noise originating in the acoustic flow resistance of the small hole pierced in the diaphragm to equalize barometric pressure. Between approximately 1 kHz and 9 kHz, the noise originates in the acoustic flow resistances of sound entering the microphone and propagating to the diaphragm. To further reduce the microphone internal noise in the audio band requires attacking these sources. A prototype microphone having reduced acoustical noise is measured and discussed.

  15. The road to miniaturization

    International Nuclear Information System (INIS)

    Iwai, Hiroshi; Hei Wong

    2006-01-01

    Silicon microelectronics has revolutionized the way we live, but how long can the relentless down sizing of devices continue? Hei Wong and Hiroshi Iwai describe the challenges facing the semiconductor industry today. For the last four decades the miniaturization of the microchip has been the driving force behind developments in all kinds of technology, from home entertainment to space exploration. At the heart of this revolution lies the metal-oxide-semiconductor (MOS) transistor, which has evolved in two ways. First, it has become smaller, with the latest devices measuring a thousandth of their original size. Second, the number of transistors that can be interconnected on a single chip has risen from a few tens to hundreds of millions. The density of microchips has followed an exponential trend that was famously identified by Gordon Moore of Intel in 1965. Moore predicted that the number of components that could be crammed into an integrated circuit would double every two years for the foreseeable future. In fact, he slightly underestimated the trend, because the average number has actually doubled every 18 months. The question keeping chip manufacturers awake in 2005 is how long this exponential growth can continue. (U.K.)

  16. The road to miniaturization

    International Nuclear Information System (INIS)

    Iwai, Hiroshi; Hei Wong

    2005-01-01

    Silicon microelectronics has revolutionized the way we live, but how long can the relentless downsizing of devices continue? Hei Wong and Hiroshi Iwai describe the challenges facing the semiconductor industry today. For the last four decades the miniaturization of the microchip has been the driving force behind developments in all kinds of technology, from home entertainment to space exploration. At the heart of this revolution lies the metal-oxide-semiconductor (MOS) transistor, which has evolved in two ways. First, it has become smaller, with the latest devices measuring a thousandth of their original size. Second, the number of transistors that can be interconnected on a single chip has risen from a few tens to hundreds of millions. The density of microchips has followed an exponential trend that was famously identified by Gordon Moore of Intel in 1965. Moore predicted that the number of components that could be crammed into an integrated circuit would double every two years for the foreseeable future. In fact, he slightly underestimated the trend, because the average number has actually doubled every 18 months. The question keeping chip manufacturers awake in 2005 is how long this exponential growth can continue. (U.K.)

  17. 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...

  18. 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...

  19. Design principles and fabrication method for a miniaturized fuel gas combustion reactor

    NARCIS (Netherlands)

    Zhao, Yiyuan; Veltkamp, Henk-Willem; de Boer, Meint J.; Zeng, Yaxiang; Groenesteijn, Jarno; Wiegerink, Remco J.; Lötters, Joost Conrad

    2017-01-01

    Wobbe Index meter is widely used to reflect the energy content and gas quality of a fuel gas mixture. It is highly in demand to downscale from the conventionally large Wobbe Index facility to a miniaturized Wobbe Index meter. Therefore spontaneously combustion of the fuel gas/air mixtures on a

  20. 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

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

    International Nuclear Information System (INIS)

    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

    2011-01-01

    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.

  2. 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.

  3. Generation of mouse and human induced pluripotent stem cells (iPSC) from primary somatic cells.

    Science.gov (United States)

    Lorenzo, I M; Fleischer, A; Bachiller, D

    2013-08-01

    Cellular reprogramming consists of the conversion of differentiated cells into pluripotent cells; the so-called induced Pluripotent Stem Cells. iPSC are amenable to in vitro manipulation and, in theory, direct production of any differentiated cell type. Furthermore, iPSC can be obtained from sick individuals and subsequently used for disease modeling, drug discovery and regenerative treatments. iPSC production was first achieved by transducing, with the use of retroviral vectors, four specific transcription factors: Oct4, Klf4, Sox2 and c-Myc (OKSM), into primary cells in culture Takahashi and Yamanaka, (Cell 126(4):663-676, 2006). Many alternative protocols have since been proposed: repeated transfections of expression plasmids containing the four pluripotency-associated genes Okita et al. (Science 322(5903):949-953, 2008), lentiviral delivery of the four factors Sommer et al. (Stem Cells 27(3):543-549, 2009), Sendai virus delivery Fusaki et al. (Proceedings of the Japan Academy. Series B, Physical and Biological Sciences 85(8):348-362, 2009), removal of the reprogramming vectors by 'piggyBac' transposition Woltjen et al. (Nature 458(7239):766-770, 2009); Kaji et al. (Nature 458(7239):771-775, 2009), Cre-recombinase excisable viruses Soldner et al. (Cell 136(5):964-977, 2009), episomal vectors Yu et al. (Science 324(5928):797-801, 2009), cell-penetrating reprogramming proteins Zhou et al. (Stem Cells 4(5):381-384, 2009), mammalian artificial chromosomes Hiratsuka et al. (PLoS One 6(10):e25961, 2011) synthetically modified mRNAs Warren et al. (Scientific Reports 2:657, 2012), miRNA Anokye-Danso et al. (Cell Stem Cell 8(4):376-388, 2009); however, although some of these methods are commercially available, in general they still need to attain the reproducibility and reprogramming efficiency required for routine applications Mochiduki and Okita (Biotechnol Journal 7(6):789-797, 2012). Herein we explain, in four detailed protocols, the isolation of mouse and human

  4. Miniature X-Ray Tubes

    Science.gov (United States)

    Bearman, Gregory H.

    1995-01-01

    Miniature x-ray tubes proposed for use in portable instruments used to analyze minerals. Electrons from field emitter (instead of thermionic emitter) accelerated to target to generate x-rays. Fabricated from silicon wafers, micromachined field emitters (MFEs) not subject to breakage or restrictions on lifetimes, and tolerate vacuums that filaments cannot. Miniature x-ray tubes very robust, immune to shock and vibration, and permanently sealed with getter for continued pumping. Combined with solid-state x-ray detectors for analysis of x-ray fluorescence.

  5. Functional Gene Correction for Cystic Fibrosis in Lung Epithelial Cells Generated from Patient iPSCs

    Directory of Open Access Journals (Sweden)

    Amy L. Firth

    2015-09-01

    Full Text Available Lung disease is a major cause of death in the United States, with current therapeutic approaches serving only to manage symptoms. The most common chronic and life-threatening genetic disease of the lung is cystic fibrosis (CF caused by mutations in the cystic fibrosis transmembrane regulator (CFTR. We have generated induced pluripotent stem cells (iPSCs from CF patients carrying a homozygous deletion of F508 in the CFTR gene, which results in defective processing of CFTR to the cell membrane. This mutation was precisely corrected using CRISPR to target corrective sequences to the endogenous CFTR genomic locus, in combination with a completely excisable selection system, which significantly improved the efficiency of this correction. The corrected iPSCs were subsequently differentiated to mature airway epithelial cells where recovery of normal CFTR expression and function was demonstrated. This isogenic iPSC-based model system for CF could be adapted for the development of new therapeutic approaches.

  6. 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.

  7. 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.

  8. 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

  9. A miniature thermoacoustic stirling engine

    International Nuclear Information System (INIS)

    Zhou Gang; Li Qing; Li Zhengyu; Li Qiang

    2008-01-01

    A miniature thermoacoustic stirling engine was simulated and designed, having overall size of length 0.65 m and height of 0.22 m. The acoustic field generated in this miniature system has been described and analyzed. Some efforts had been paid to coupling and matching, and a miniature thermoacoustic engine and some extra experimental components have been constructed. Analysis and experimental results showed that to obtain better performance of the engine, the diameter of the resonance tube must be chosen appropriately according to the looped tube dimension and the input heating power. It provided an effective way to miniaturize the thermoacoustic stirling heat engine. The experimental results showed that the engine had low onset temperature and high pressure amplitude and ratio. With the filling helium gas of 2 MPa and heating power of 637 W, the maximal peak to peak pressure amplitude and pressure ratio reached 2.2 bar and 1.116, respectively, which was able to drive a refrigerator, a heat pump or a linear electrical generator. The operating frequency of the engine was steady at 282 Hz

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

    Science.gov (United States)

    Nagode, Daniel A; Tang, Ai-Hui; Karson, Miranda A; Klugmann, Matthias; Alger, Bradley E

    2011-01-01

    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 may be a

  11. 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...

  12. All Roads Lead to Induced Pluripotent Stem Cells: The Technologies of iPSC Generation

    Science.gov (United States)

    2014-01-01

    Generation of induced pluripotent stem cells (iPSCs) via the ectopic expression of reprogramming factors is a simple, advanced, yet often perplexing technology due to low efficiency, slow kinetics, and the use of numerous distinct systems for factor delivery. Scientists have used almost all available approaches for the delivery of reprogramming factors. Even the well-established retroviral vectors confuse some scientists due to different tropisms in use. The canonical virus-based reprogramming poses many problems, including insertional mutagenesis, residual expression and re-activation of reprogramming factors, uncontrolled silencing of transgenes, apoptosis, cell senescence, and strong immunogenicity. To eliminate or alleviate these problems, scientists have tried various other approaches for factor delivery and transgene removal. These include transient transfection, nonintegrating viral vectors, Cre-loxP excision of transgenes, excisable transposon, protein transduction, RNA transfection, microRNA transfection, RNA virion, RNA replicon, nonintegrating replicating episomal plasmids, minicircles, polycistron, and preintegration of inducible reprogramming factors. These alternative approaches have their own limitations. Even iPSCs generated with RNA approaches should be screened for possible transgene insertions mediated by active endogenous retroviruses in the human genome. Even experienced researchers may encounter difficulty in selecting and using these different technologies. This survey presents overviews of iPSC technologies with the intention to provide a quick yet comprehensive reference for both new and experienced reprogrammers. PMID:24524728

  13. 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

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Derivation of iPSCs after culture of human dental pulp cells under defined conditions.

    Directory of Open Access Journals (Sweden)

    Tomoko Takeda-Kawaguchi

    Full Text Available Human dental pulp cells (hDPCs are a promising resource for regenerative medicine and tissue engineering and can be used for derivation of induced pluripotent stem cells (iPSCs. However, current protocols use reagents of animal origin (mainly fetal bovine serum, FBS that carry the potential risk of infectious diseases and unwanted immunogenicity. Here, we report a chemically defined protocol to isolate and maintain the growth and differentiation potential of hDPCs. hDPCs cultured under these conditions showed significantly less primary colony formation than those with FBS. Cell culture under stringently defined conditions revealed a donor-dependent growth capacity; however, once established, the differentiation capabilities of the hDPCs were comparable to those observed with FBS. DNA array analyses indicated that the culture conditions robustly altered hDPC gene expression patterns but, more importantly, had little effect on neither pluripotent gene expression nor the efficiency of iPSC induction. The chemically defined culture conditions described herein are not perfect serum replacements, but can be used for the safe establishment of iPSCs and will find utility in applications for cell-based regenerative medicine.

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

    Science.gov (United States)

    Milagre, Inês; Stubbs, Thomas M; King, Michelle R; Spindel, Julia; Santos, Fátima; Krueger, Felix; Bachman, Martin; Segonds-Pichon, Anne; Balasubramanian, Shankar; Andrews, Simon R; Dean, Wendy; Reik, Wolf

    2017-01-31

    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. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. A Comparative View on Easy to Deploy non-Integrating Methods for Patient-Specific iPSC Production

    OpenAIRE

    Manzini, Stefano; Viiri, Leena E.; Marttila, Suvi; Aalto-Set?l?, Katriina

    2015-01-01

    Induced pluripotent stem cells (iPSCs) are routinely produced from dermal fibroblasts, with potential applications ranging from in vitro disease models to drug discovery and regenerative medicine. The need of eliminating the remaining reprogramming factors after iPSC production spurred the development of non-integrating viruses such as Sendai and other methods to deliver episomal vectors, which are progressively lost upon cell division. We compared four widespread methods (Sendai virus, Nucle...

  20. Alcohol Increases Liver Progenitor Populations and Induces Disease Phenotypes in Human IPSC-Derived Mature Stage Hepatic Cells

    OpenAIRE

    Tian, Lipeng; Deshmukh, Abhijeet; Prasad, Neha; Jang, Yoon-Young

    2016-01-01

    Alcohol consumption has long been a global problem affecting human health, and has been found to influence both fetal and adult liver functions. However, how alcohol affects human liver development and liver progenitor cells remains largely unknown. Here, we used human induced pluripotent stem cells (iPSCs) as a model to examine the effects of alcohol, on multi-stage hepatic cells including hepatic progenitors, early and mature hepatocyte-like cells derived from human iPSCs. While alcohol has...

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. 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.

  4. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Ribeiro, Diana; Andersson, Eva-Marie; Heath, Nikki; Persson-Kry, Anette; Collins, Richard; Hicks, Ryan; Dekker, Niek; Forslöw, Anna

    2017-01-01

    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.

  7. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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...

  10. Spontaneous body movements in spatial cognition

    Directory of Open Access Journals (Sweden)

    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.

  11. 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)

  12. Gammaretroviral vector encoding a fluorescent marker to facilitate detection of reprogrammed human fibroblasts during iPSC generation

    Directory of Open Access Journals (Sweden)

    Narasimhachar Srinivasakumar

    2013-12-01

    Full Text Available Induced pluripotent stem cells (iPSCs are becoming mainstream tools to study mechanisms of development and disease. They have a broad range of applications in understanding disease processes, in vitro testing of novel therapies, and potential utility in regenerative medicine. Although the techniques for generating iPSCs are becoming more straightforward, scientists can expend considerable resources and time to establish this technology. A major hurdle is the accurate determination of valid iPSC-like colonies that can be selected for further cloning and characterization. In this study, we describe the use of a gammaretroviral vector encoding a fluorescent marker, mRFP1, to not only monitor the efficiency of initial transduction but also to identify putative iPSC colonies through silencing of mRFP1 gene as a consequence of successful reprogramming.

  13. Functional Characterization of IPSC-Derived Brain Cells as a Model for X-Linked Adrenoleukodystrophy.

    Directory of Open Access Journals (Sweden)

    Mauhamad Baarine

    Full Text Available X-ALD is an inherited neurodegenerative disorder where mutations in the ABCD1 gene result in clinically diverse phenotypes: the fatal disorder of cerebral childhood ALD (cALD or a milder disorder of adrenomyeloneuropathy (AMN. The various models used to study the pathobiology of X-ALD disease lack the appropriate presentation for different phenotypes of cALD vs AMN. This study demonstrates that induced pluripotent stem cells (IPSC derived brain cells astrocytes (Ast, neurons and oligodendrocytes (OLs express morphological and functional activities of the respective brain cell types. The excessive accumulation of saturated VLCFA, a "hallmark" of X-ALD, was observed in both AMN OLs and cALD OLs with higher levels observed in cALD OLs than AMN OLs. The levels of ELOVL1 (ELOVL Fatty Acid Elongase 1 mRNA parallel the VLCFA load in AMN and cALD OLs. Furthermore, cALD Ast expressed higher levels of proinflammatory cytokines than AMN Ast and control Ast with or without stimulation with lipopolysaccharide. These results document that IPSC-derived Ast and OLs from cALD and AMN fibroblasts mimic the respective biochemical disease phenotypes and thus provide an ideal platform to investigate the mechanism of VLCFA load in cALD OLs and VLCFA-induced inflammatory disease mechanisms of cALD Ast and thus for testing of new therapeutics for AMN and cALD disease of X-ALD.

  14. 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.

  15. Nanog-Independent Reprogramming to iPSCs with Canonical Factors

    Directory of Open Access Journals (Sweden)

    Ava C. Carter

    2014-02-01

    Full Text Available It has been suggested that the transcription factor Nanog is essential for the establishment of pluripotency during the derivation of embryonic stem cells and induced pluripotent stem cells (iPSCs. However, successful reprogramming to pluripotency with a growing list of divergent transcription factors, at ever-increasing efficiencies, suggests that there may be many distinct routes to a pluripotent state. Here, we have investigated whether Nanog is necessary for reprogramming murine fibroblasts under highly efficient conditions using the canonical-reprogramming factors Oct4, Sox2, Klf4, and cMyc. In agreement with prior results, the efficiency of reprogramming Nanog−/− fibroblasts was significantly lower than that of control fibroblasts. However, in contrast to previous findings, we were able to reproducibly generate iPSCs from Nanog−/− fibroblasts that effectively contributed to the germline of chimeric mice. Thus, whereas Nanog may be an important mediator of reprogramming, it is not required for establishing pluripotency in the mouse, even under standard conditions.

  16. 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.

  17. Generation of neural cells using iPSCs from sleep bruxism patients with 5-HT2A polymorphism.

    Science.gov (United States)

    Hoashi, Yurie; Okamoto, Satoshi; Abe, Yuka; Matsumoto, Takashi; Tanaka, Junichi; Yoshida, Yuya; Imaizumi, Kent; Mishima, Kenji; Akamatsu, Wado; Okano, Hideyuki; Baba, Kazuyoshi

    2017-07-01

    Sleep bruxism (SB) is classified as a sleep-related movement disorder characterized by grinding and clenching of the teeth during sleep, which is responsible for a variety of clinical problems such as abnormal tooth attrition and fracture of teeth or roots. Little is known about the etiology of SB. Our previous study identified a genomic association of the serotonin 2A receptor (5-HT2A) single nucleotide polymorphism (SNP), rs6313 C>T, with SB, where the C allele carrier is associated with a 4.25-fold increased risk of SB. Based on this finding, the aim of this study was to generate of neural cells using SB patient-specific induced pluripotent stem cells (iPSCs). Two SB patients with C/C genotype of rs6313 and two controls with T/T genotype were screened by laboratory-based polysomnographic recordings and the TaqMan genotyping assay. Four lines of iPSCs, two from SB patients and two from controls, were established from peripheral blood mononuclear cells by introduction of reprogramming factors. We performed quality control assays on iPSCs using expression of markers for undifferentiated pluripotent cells, immunostaining for pluripotency markers, a three-germ layer assay, and karyotype analysis. The established iPSCs were differentiated into neurons using the neurosphere culture system. 5-HT2A gene expression in these neurons was evaluated by quantitative real-time PCR. Patient-specific iPSCs were successfully differentiated into neurons expressing 5-HT2A. This report is the first successful generation of neural cells using iPSCs from sleep bruxism patients with 5-HT2A polymorphism, which has the potential to elucidate the etiology and underlying mechanism of SB. Copyright © 2016 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  18. Peripheral blood derived induced pluripotent stem cells (iPSCs from a female with familial hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Samantha Barratt Ross

    2017-04-01

    Full Text Available Induced pluripotent stem cells (iPSCs were generated from peripheral blood mononuclear cells (PBMCs obtained from a 62-year-old female with familial hypertrophic cardiomyopathy (HCM. PBMCs were reprogrammed to a pluripotent state following transfection with non-integrative episomal vectors carrying reprogramming factors OCT4, SOX2, LIN28, KLF4 and L-MYC. iPSCs were shown to express pluripotency markers, possess trilineage differentiation potential, carry rare variants identified in DNA isolated directly from the patient's whole blood, have a normal karyotype and no longer carry episomal vectors for reprogramming. This line is a useful resource for identifying unknown genetic causes of HCM.

  19. Generation of Xeno-Free, cGMP-Compliant Patient-Specific iPSCs from Skin Biopsy.

    Science.gov (United States)

    Wiley, Luke A; Anfinson, Kristin R; Cranston, Cathryn M; Kaalberg, Emily E; Collins, Malia M; Mullins, Robert F; Stone, Edwin M; Tucker, Budd A

    2017-08-14

    This unit describes protocols for the generation of clinical-grade patient-specific induced pluripotent stem cell (iPSC)-derived retinal cells from patients with inherited retinal degenerative blindness. Specifically, we describe how, using xeno-free reagents in an ISO class 5 environment, one can isolate and culture dermal fibroblasts, generate iPSCs, and derive autologous retinal cells via 3-D differentiation. The universal methods described herein for the isolation of dermal fibroblasts and generation of iPSCs can be employed regardless of disease, tissue, or cell type of interest. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  20. Glomerular Lesions in Proteinuric Miniature Schnauzer Dogs

    OpenAIRE

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

    2016-01-01

    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 l...

  1. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H266

    DEFF Research Database (Denmark)

    Marthaler, Adele Gabriele; Tubsuwan, Alisa; Schmid, Benjamin

    2016-01-01

    (iPSC) lines of SCA2 patients in order to study a disease-specific phenotype. Here, we demonstrate the gene correction of the iPSC line H266 clone 10 where we have exchanged the expanded CAG repeat of the ATXN2 gene with the normal length found in healthy alleles. This gene corrected cell line...

  2. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H196

    DEFF Research Database (Denmark)

    Marthaler, Adele Gabriele; Schmid, Benjamin; Tubsuwan, Alisa

    2016-01-01

    (iPSC) lines of SCA2 patients in order to study a disease-specific phenotype. Here, we demonstrate the gene correction of the iPSC line H196 clone 7 where we have exchanged the expanded CAG repeat of the ATXN2 gene with the normal length found in healthy alleles. This gene corrected cell line...

  3. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H271

    DEFF Research Database (Denmark)

    Marthaler, Adele Gabriele; Schmid, Benjamin; Tubsuwan, Alisa

    2016-01-01

    (iPSC) lines of SCA2 patients in order to study a disease-specific phenotype. Here, we demonstrate the gene correction of the iPSC line H271 clone 1 where we have exchanged the expanded CAG repeat of the ATXN2 gene with the normal length found in healthy alleles. This gene corrected cell line...

  4. 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.

  5. Advances in Miniaturized Instruments for Genomics

    Science.gov (United States)

    2014-01-01

    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. PMID:25114919

  6. Comparative effects of pentobarbital on spontaneous and evoked transmitter release from inhibitory and excitatory nerve terminals in rat CA3 neurons.

    Science.gov (United States)

    Shin, Min-Chul; Wakita, Masahito; Iwata, Satomi; Nonaka, Kiku; Kotani, Naoki; Akaike, Norio

    2013-01-01

    Pentobarbital (PB) modulates GABA(A) receptor-mediated postsynaptic responses through various mechanisms, and can directly activate the channel at higher doses. These channels exist both pre- and postsynaptically, and on the soma outside the synapse. PB also inhibits voltage-dependent Na⁺ and Ca²⁺ channels to decrease excitatory synaptic transmission. Just how these different sites of action combine to contribute to the overall effects of PB on inhibitory and excitatory synaptic transmission is less clear. To compare these pre- and postsynaptic actions of PB, we used a 'synaptic bouton' preparation of isolated rat hippocampal CA3 pyramidal neurons where we could measure in single neurons the effects of PB on spontaneous and single bouton evoked GABAergic inhibitory and glutamatergic excitatory postsynaptic currents (sIPSCs, sEPSCs, eIPSCs and eEPSCs), respectively. Low (sedative) concentrations (3-10 μM) of PB increased the frequency and amplitude of sIPSCs and sEPSCs, and also presynaptically increased the amplitude of both eIPSCs and eEPSCs. There was no change in current kinetics at this low concentration. At higher concentrations (30-300 μM), PB decreased the frequency, and increased the amplitude of sIPSCs, and presynaptically decreased the amplitude of eIPSCs. The current decay phase of sIPSCs and eIPSCs was increased. An increase in both frequency and amplitude was seen for sEPSCs, while the eIPSCs was also decreased by a bicuculline-sensitive presynaptic effect. The results confirm the multiple sites of action of PB on inhibitory and excitatory transmission and demonstrate that the most sensitive site of action is on transmitter release, via effects on presynaptic GABA(A) receptors. At low concentrations, however, both glutamate and GABA release is similarly enhanced, making the final effects on neuronal excitability difficult to predict and dependent on the particular systems involved and/or on subtle differences in susceptibility amongst

  7. Studying arrhythmogenic right ventricular dysplasia with patient-specific iPSCs.

    Science.gov (United States)

    Kim, Changsung; Wong, Johnson; Wen, Jianyan; Wang, Shirong; Wang, Cheng; Spiering, Sean; Kan, Natalia G; Forcales, Sonia; Puri, Pier Lorenzo; Leone, Teresa C; Marine, Joseph E; Calkins, Hugh; Kelly, Daniel P; Judge, Daniel P; Chen, Huei-Sheng Vincent

    2013-02-07

    Cellular reprogramming of somatic cells to patient-specific induced pluripotent stem cells (iPSCs) enables in vitro modelling of human genetic disorders for pathogenic investigations and therapeutic screens. However, using iPSC-derived cardiomyocytes (iPSC-CMs) to model an adult-onset heart disease remains challenging owing to the uncertainty regarding the ability of relatively immature iPSC-CMs to fully recapitulate adult disease phenotypes. Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited heart disease characterized by pathological fatty infiltration and cardiomyocyte loss predominantly in the right ventricle, which is associated with life-threatening ventricular arrhythmias. Over 50% of affected individuals have desmosome gene mutations, most commonly in PKP2, encoding plakophilin-2 (ref. 9). The median age at presentation of ARVD/C is 26 years. We used previously published methods to generate iPSC lines from fibroblasts of two patients with ARVD/C and PKP2 mutations. Mutant PKP2 iPSC-CMs demonstrate abnormal plakoglobin nuclear translocation and decreased β-catenin activity in cardiogenic conditions; yet, these abnormal features are insufficient to reproduce the pathological phenotypes of ARVD/C in standard cardiogenic conditions. Here we show that induction of adult-like metabolic energetics from an embryonic/glycolytic state and abnormal peroxisome proliferator-activated receptor gamma (PPAR-γ) activation underlie the pathogenesis of ARVD/C. By co-activating normal PPAR-alpha-dependent metabolism and abnormal PPAR-γ pathway in beating embryoid bodies (EBs) with defined media, we established an efficient ARVD/C in vitro model within 2 months. This model manifests exaggerated lipogenesis and apoptosis in mutant PKP2 iPSC-CMs. iPSC-CMs with a homozygous PKP2 mutation also had calcium-handling deficits. Our study is the first to demonstrate that induction of adult-like metabolism has a critical role in establishing an

  8. 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.

  9. Alcohol Increases Liver Progenitor Populations and Induces Disease Phenotypes in Human IPSC-Derived Mature Stage Hepatic Cells.

    Science.gov (United States)

    Tian, Lipeng; Deshmukh, Abhijeet; Prasad, Neha; Jang, Yoon-Young

    2016-01-01

    Alcohol consumption has long been a global problem affecting human health, and has been found to influence both fetal and adult liver functions. However, how alcohol affects human liver development and liver progenitor cells remains largely unknown. Here, we used human induced pluripotent stem cells (iPSCs) as a model to examine the effects of alcohol, on multi-stage hepatic cells including hepatic progenitors, early and mature hepatocyte-like cells derived from human iPSCs. While alcohol has little effect on endoderm development from iPSCs, it reduces formation of hepatic progenitor cells during early hepatic specification. The proliferative activities of early and mature hepatocyte-like cells are significantly decreased after alcohol exposure. Importantly, at a mature stage of hepatocyte-like cells, alcohol treatment increases two liver progenitor subsets, causes oxidative mitochondrial injury and results in liver disease phenotypes (i.e., steatosis and hepatocellular carcinoma associated markers) in a dose dependent manner. Some of the phenotypes were significantly improved by antioxidant treatment. This report suggests that fetal alcohol exposure may impair generation of hepatic progenitors at early stage of hepatic specification and decrease proliferation of fetal hepatocytes; meanwhile alcohol injury in post-natal or mature stage human liver may contribute to disease phenotypes. This human iPSC model of alcohol-induced liver injury can be highly valuable for investigating alcoholic injury in the fetus as well as understanding the pathogenesis and ultimately developing effective treatment for alcoholic liver disease in adults.

  10. Derivation of Human Induced Pluripotent Stem Cell (iPSC) Lines and Mechanism of Pluripotency: Historical Perspective and Recent Advances.

    Science.gov (United States)

    Chhabra, Arvind

    2017-12-01

    Derivation of human embryonic stem cell (hES) lines in 1998 was not only a major technological breakthrough in the field of regenerative medicine; it also triggered a passionate debate about the ethical issues associated with the utilization of human embryos for derivation of hESC lines. Successful derivation of induced pluripotent stem cell (iPS) lines from human somatic cells with defined reprogramming factors by Shinya Yamanaka`s group in 2007 was another breakthrough that generated enormous excitement and hope for the development of donor-specific personalized cell replacement therapies (CRT) without the ethical dilemma associated with it. As we approach twentieth anniversary of derivation of hESC lines and the tenth anniversary of isolation of donor-specific iPSC lines, this manuscript summarizes the key advances in pluripotent stem cell (PSC) research field that led to derivation of human iPSC lines, different methodologies for derivation iPSC lines and characterization of the mechanism of reprogramming. We will also review progress towards generating donor-specific somatic cell lineages from iPSC lines, especially the functional immune cell lineages, and progress towards advancing these findings to the clinic. Finally, we will discuss the challenges, such as genome instability and inherent immunogenicity of hPSC lines that need to be addressed to develop safe and effective iPSC-based CRT.

  11. Establishment of a human iPSC line (IISHDOi001-A from a patient with McArdle disease

    Directory of Open Access Journals (Sweden)

    María del Carmen Ortuño-Costela

    2017-08-01

    Full Text Available Human iPSC line IISHDOi001-A was generated from fibroblasts of a patient with McArdle disease harbouring the mutation, c.148C>T; p.Arg50Ter, in the PYGM gene. Reprogramming factors Oct3/4, Sox2, Klf4, and c-Myc were delivered using Sendai virus.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Generation of iPSCs from genetically corrected Brca2 hypomorphic cells: implications in cell reprogramming and stem cell therapy.

    Science.gov (United States)

    Navarro, S; Moleiro, V; Molina-Estevez, F J; Lozano, M L; Chinchon, R; Almarza, E; Quintana-Bustamante, O; Mostoslavsky, G; Maetzig, T; Galla, M; Heinz, N; Schiedlmeier, B; Torres, Y; Modlich, U; Samper, E; Río, P; Segovia, J C; Raya, A; Güenechea, G; Izpisua-Belmonte, J C; Bueren, J A

    2014-02-01

    Fanconi anemia (FA) is a complex genetic disease associated with a defective DNA repair pathway known as the FA pathway. In contrast to many other FA proteins, BRCA2 participates downstream in this pathway and has a critical role in homology-directed recombination (HDR). In our current studies, we have observed an extremely low reprogramming efficiency in cells with a hypomorphic mutation in Brca2 (Brca2(Δ) (27/) (Δ27)), that was associated with increased apoptosis and defective generation of nuclear RAD51 foci during the reprogramming process. Gene complementation facilitated the generation of Brca2(Δ) (27/) (Δ27) induced pluripotent stem cells (iPSCs) with a disease-free FA phenotype. Karyotype analyses and comparative genome hybridization arrays of complemented Brca2(Δ) (27/) (Δ27) iPSCs showed, however, the presence of different genetic alterations in these cells, most of which were not evident in their parental Brca2(Δ) (27/) (Δ27) mouse embryonic fibroblasts. Gene-corrected Brca2(Δ) (27/) (Δ27) iPSCs could be differentiated in vitro toward the hematopoietic lineage, although with a more limited efficacy than WT iPSCs or mouse embryonic stem cells, and did not engraft in irradiated Brca2(Δ) (27/) (Δ27) recipients. Our results are consistent with previous studies proposing that HDR is critical for cell reprogramming and demonstrate that reprogramming defects characteristic of Brca2 mutant cells can be efficiently overcome by gene complementation. Finally, based on analysis of the phenotype, genetic stability, and hematopoietic differentiation potential of gene-corrected Brca2(Δ) (27/) (Δ) (27) iPSCs, achievements and limitations in the application of current reprogramming approaches in hematopoietic stem cell therapy are also discussed. © AlphaMed Press.

  15. 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.

  16. 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.

  17. Scanning Miniature Microscopes without Lenses

    Science.gov (United States)

    Wang, Yu

    2009-01-01

    The figure schematically depicts some alternative designs of proposed compact, lightweight optoelectronic microscopes that would contain no lenses and would generate magnified video images of specimens. Microscopes of this type were described previously in Miniature Microscope Without Lenses (NPO - 20218), NASA Tech Briefs, Vol. 22, No. 8 (August 1998), page 43 and Reflective Variants of Miniature Microscope Without Lenses (NPO 20610), NASA Tech Briefs, Vol. 26, No. 9 (September 1999), page 6a. To recapitulate: In the design and construction of a microscope of this type, the focusing optics of a conventional microscope are replaced by a combination of a microchannel filter and a charge-coupled-device (CCD) image detector. Elimination of focusing optics reduces the size and weight of the instrument and eliminates the need for the time-consuming focusing operation. The microscopes described in the cited prior articles contained two-dimensional CCDs registered with two-dimensional arrays of microchannels and, as such, were designed to produce full two-dimensional images, without need for scanning. The microscopes of the present proposal would contain one-dimensional (line image) CCDs registered with linear arrays of microchannels. In the operation of such a microscope, one would scan a specimen along a line perpendicular to the array axis (in other words, one would scan in pushbroom fashion). One could then synthesize a full two-dimensional image of the specimen from the line-image data acquired at one-pixel increments of position along the scan. In one of the proposed microscopes, a beam of unpolarized light for illuminating the specimen would enter from the side. This light would be reflected down onto the specimen by a nonpolarizing beam splitter attached to the microchannels at their lower ends. A portion of the light incident on the specimen would be reflected upward, through the beam splitter and along the microchannels, to form an image on the CCD. If the

  18. Miniaturized High Performance Optical Gyroscope Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose a new approach for to the design and fabrication of miniaturized Interferometric Fiber Optical Gyroscope (FOG) that enables the production of smaller IRU...

  19. Miniature Laser Magnetometer (MLM), Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This 2009 NASA SBIR Phase 1 proposal for an innovative Miniature Laser Magnetometer (MLM) is a response to subtopic S1.06 Particles and Field Sensors and Instrument...

  20. Miniaturized Airborne Imaging Central Server System Project

    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 Project

    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. 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,...

  3. Miniature Laser Magnetometer (MLM), Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — This 2009 NASA SBIR Phase 2 proposal for an innovative Miniature Laser Magnetometer (MLM) is a response to subtopic S1.06 Particles and Field Sensors and Instrument...

  4. Accurate, Miniature Attitude Determination System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The overall goal of this project is to design, develop, and demonstrate using a flight test, a miniature, high accuracy attitude determination system (ADS) for use...

  5. Development of miniature bending fatigue specimens

    International Nuclear Information System (INIS)

    Rao, G.R.; Chin, B.A.; Rowcliffe, A.

    1991-01-01

    Two new miniaturized bending fatigue specimens have been designed and developed to aid in the scoping of materials for fusion first-wall and blanket structural applications. One of these is rectangular in shape with a gauge section 6.35 mm in length, while the other is cut from a 3 mm transmission electron microscopy (TEM) disk and has a gauge length of 1.5 mm. Test rules for unirradiated annealed type 316 stainless steel tested at room temperature, 550deg C and 650deg C are presented. A good correlation between miniature and standard subsize fatigue specimen results was obtained. The miniature specimen results show the same dependence of strain range on cycles to failure as the standard subsize specimens with the miniature-disk specimen results falling below all the other results. The results indicate that these specimens provide reliable data that can be used to scope fatigue properties for fusion applications. (orig.)

  6. 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...

  7. Miniature Sensor for Aerosol Mass Measurements Project

    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...

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

    Science.gov (United States)

    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

  9. 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.

  10. 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...

  11. Design and performance optimization of miniature heat pipes in LTCC

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Peter Z; Chua, K M; Wong, Stephen C K; Tan, Y M [Singapore Institute of Manufacturing Technology 71 Nanyang Drive, Singapore 638075 (Singapore)

    2006-04-01

    In this paper, performance evaluation of miniature heat pipes in LTCC was made by numerical analysis, and the optimum miniature heat pipe design was defined. The effect of the groove depth, width and vapor space on the heat transfer capacity of miniature heat pipes was analyzed. Prototypes of the miniature heat pipes in LTCC were fabricated. Preliminary charging, sealing and thermal measurement of the miniature heat pipes were performed, and the challenges were discussed.

  12. A miniature electrical capacitance tomograph

    Science.gov (United States)

    York, T. A.; Phua, T. N.; Reichelt, L.; Pawlowski, A.; Kneer, R.

    2006-08-01

    The paper describes a miniature electrical capacitance tomography system. This is based on a custom CMOS silicon integrated circuit comprising eight channels of signal conditioning electronics to source drive signals and measure voltages. Electrodes are deposited around a hole that is fabricated, using ultrasonic drilling, through a ceramic substrate and has an average diameter of 0.75 mm. The custom chip is interfaced to a host computer via a bespoke data acquisition system based on a microcontroller, field programmable logic device and wide shift register. This provides fast capture of up to 750 frames of data prior to uploading to the host computer. Data capture rates of about 6000 frames per second have been achieved for the eight-electrode sensor. This rate could be increased but at the expense of signal to noise. Captured data are uploaded to a PC, via a RS232 interface, for off-line imaging. Initial tests are reported for the static case involving 200 µm diameter rods that are placed in the sensor and for the dynamic case using the dose from an inhaler.

  13. Drilling miniature holes, Part III

    Energy Technology Data Exchange (ETDEWEB)

    Gillespie, L.K.

    1978-07-01

    Miniature components for precision electromechanical mechanisms such as switches, timers, and actuators typically require a number of small holes. Because of the precision required, the workpiece materials, and the geometry of the parts, most of these holes must be produced by conventional drilling techniques. The use of such techniques is tedious and often requires considerable trial and error to prevent drill breakage, minimize hole mislocation and variations in hole diameter. This study of eight commercial drill designs revealed that printed circuit board drills produced better locational and size repeatability than did other drills when centerdrilling was not used. Boring holes 1 mm in dia, or less, as a general rule did not improve hole location in brass or stainless steel. Hole locations of patterns of 0.66-mm holes can be maintained within 25.4-..mu..m diametral positional tolerance if setup misalignments can be eliminated. Size tolerances of +- 3.8 ..mu..m can be maintained under some conditions when drilling flat plates. While these levels of precision are possible with existing off-the-shelf drills, they may not be practical in many cases.

  14. Spontaneous pneumothorax in weightlifters.

    Science.gov (United States)

    Marnejon, T; Sarac, S; Cropp, A J

    1995-06-01

    Spontaneous pneumothorax is infrequently caused by strenuous exertion. To our knowledge there has only been one case of spontaneous pneumothorax associated with weightlifting reported in the medical literature. We describe three consecutive cases of spontaneous pneumothorax associated with weightlifting. We postulate that spontaneous pneumothorax in these patients may be secondary to improper breathing techniques. It is important that physicians and weight trainers be aware of the association between weight lifting and spontaneous pneumothorax and assure that proper instruction is given to athletes who work with weights.

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

    DEFF Research Database (Denmark)

    Wierda, Keimpe D B; Sørensen, Jakob Balslev

    2014-01-01

    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......EPSC frequencies were increased by a factor of four in the synaptotagmin-1-null neurons, which is in line with data obtained from mixed cultures. The effect persisted after incubation with BAPTA-AM. We conclude that spontaneous GABA release exerts control over mEPSC release, and GABAergic innervation...

  16. Using Oct4:MerCreMer Lineage Tracing to Monitor Endogenous Oct4 Expression During the Reprogramming of Fibroblasts into Induced Pluripotent Stem Cells (iPSCs).

    Science.gov (United States)

    Greder, Lucas V; Post, Jason; Dutton, James R

    2016-01-01

    The reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) using a combination of defined transcription factors has become one of the most widely used techniques in stem cell biology. A critical, early event in iPSC reprogramming is the induction of the endogenous transcription factor network that maintains pluripotency in iPSCs. Here we describe using a transgenic, conditional Oct4-Cre construct to investigate the spatial and temporal induction of endogenous Oct4 expression during the reprogramming of mouse fibroblasts into iPS cells.

  17. 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 dogs with HTG and absent from all dogs without HTG (P dogs were not azotemic or hypoalbuminemic. Dogs with HTG had a 65% reduction in LPL activity relative to dogs without HTG (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.

  18. Miniature EVA Software Defined Radio

    Science.gov (United States)

    Pozhidaev, Aleksey

    2012-01-01

    As NASA embarks upon developing the Next-Generation Extra Vehicular Activity (EVA) Radio for deep space exploration, the demands on EVA battery life will substantially increase. The number of modes and frequency bands required will continue to grow in order to enable efficient and complex multi-mode operations including communications, navigation, and tracking applications. Whether conducting astronaut excursions, communicating to soldiers, or first responders responding to emergency hazards, NASA has developed an innovative, affordable, miniaturized, power-efficient software defined radio that offers unprecedented power-efficient flexibility. This lightweight, programmable, S-band, multi-service, frequency- agile EVA software defined radio (SDR) supports data, telemetry, voice, and both standard and high-definition video. Features include a modular design, an easily scalable architecture, and the EVA SDR allows for both stationary and mobile battery powered handheld operations. Currently, the radio is equipped with an S-band RF section. However, its scalable architecture can accommodate multiple RF sections simultaneously to cover multiple frequency bands. The EVA SDR also supports multiple network protocols. It currently implements a Hybrid Mesh Network based on the 802.11s open standard protocol. The radio targets RF channel data rates up to 20 Mbps and can be equipped with a real-time operating system (RTOS) that can be switched off for power-aware applications. The EVA SDR's modular design permits implementation of the same hardware at all Network Nodes concept. This approach assures the portability of the same software into any radio in the system. It also brings several benefits to the entire system including reducing system maintenance, system complexity, and development cost.

  19. Induced pluripotent stem cells (iPSCs derived from cerebrotendinous xanthomatosis (CTX patient's fibroblasts carrying a R395S mutation

    Directory of Open Access Journals (Sweden)

    Philip Höflinger

    2016-09-01

    Full Text Available Induced pluripotent stem cells (iPSCs were generated from dermal fibroblasts from a 60-year-old cerebrotendinous xanthomatosis (CTX patient, carrying a homozygous mutation c. [1183C>A]; p. R395S in CYP27A1. Episomal plasmids encoding the pluripotency genes OCT4, SOX2, KLF4, L-MYC and LIN28 were introduced via electroporation. The generated line iPS-CTX-R395S has no sign of plasmid integration or chromosomal aberration and retained the mutation site in CYP27A1. Furthermore, iPSCs express pluripotency markers and are able to differentiate in all germ layers in vitro. The generated line may be a useful tool for disease modelling of CTX.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. Utilizing induced pluripotent stem cells (iPSCs) to understand the actions of estrogens in human neurons.

    Science.gov (United States)

    Shum, Carole; Macedo, Sara C; Warre-Cornish, Katherine; Cocks, Graham; Price, Jack; Srivastava, Deepak P

    2015-08-01

    This article is part of a Special Issue "Estradiol and Cognition". Over recent years tremendous progress has been made towards understanding the molecular and cellular mechanism by which estrogens exert enhancing effects on cognition, and how they act as a neuroprotective or neurotrophic agent in disease. Currently, much of this work has been carried out in animal models with only a limited number of studies using native human tissue or cells. Recent advances in stem cell technology now make it possible to reprogram somatic cells from humans into induced pluripotent stem cells (iPSCs), which can subsequently be differentiated into neurons of specific lineages. Importantly, the reprogramming of cells allows for the generation of iPSCs that retain the genetic "makeup" of the donor. Therefore, it is possible to generate iPSC-derived neurons from patients diagnosed with specific diseases, that harbor the complex genetic background associated with the disorder. Here, we review the iPSC technology and how it's currently being used to model neural development and neurological diseases. Furthermore, we explore whether this cellular system could be used to understand the role of estrogens in human neurons, and present preliminary data in support of this. We further suggest that the use of iPSC technology offers a novel system to not only further understand estrogens' effects in human cells, but also to investigate the mechanism by which estrogens are beneficial in disease. Developing a greater understanding of these mechanisms in native human cells will also aid in the development of safer and more effective estrogen-based therapeutics. Copyright © 2015. Published by Elsevier Inc.

  3. 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....

  4. Naive-like ESRRB+ iPSCs with the Capacity for Rapid Neural Differentiation

    Directory of Open Access Journals (Sweden)

    Fumihiko Kisa

    2017-12-01

    Full Text Available Summary: Several groups have reported the existence of a form of pluripotency that resembles that of mouse embryonic stem cells (mESCs, i.e., a naive state, in human pluripotent stem cells; however, the characteristics vary between reports. The nuclear receptor ESRRB is expressed in mESCs and plays a significant role in their self-renewal, but its expression has not been observed in most naive-like human induced pluripotent stem cells (hiPSCs. In this study, we modified several methods for converting hiPSCs into a naive state through the transgenic expression of several reprogramming factors. The resulting cells express the components of the core transcriptional network of mESCs, including ESRRB, at high levels, which suggests the existence of naive-state hiPSCs that are similar to mESCs. We also demonstrate that these cells differentiate more readily into neural cells than do conventional hiPSCs. These features may be beneficial for their use in disease modeling and regenerative medicine. : Kisa et al. modified several methods for converting human induced pluripotent stem cells (hiPSCs into a naive state, a form of pluripotency that exists in mouse embryonic stem cells (ESCs. Converted cells express components of the core transcriptional network upregulated in mouse ESCs, including ESRRB. They also show that these cells differentiate more readily into neural cells than do conventional hiPSCs. Keywords: naive pluripotency, human iPSC, reprogramming, neural differentiation

  5. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  7. The miR-302-Mediated Induction of Pluripotent Stem Cells (iPSC): Multiple Synergistic Reprogramming Mechanisms.

    Science.gov (United States)

    Ying, Shao-Yao; Fang, William; Lin, Shi-Lung

    2018-01-01

    Pluripotency represents a unique feature of embryonic stem cells (ESCs). To generate ESC-like-induced pluripotent stem cells (iPSCs) derived from somatic cells, the cell genome needs to be reset and reprogrammed to express the ESC-specific transcriptome. Numerous studies have shown that genomic DNA demethylation is required for epigenetic reprogramming of somatic cell nuclei to form iPSCs; yet, the mechanism remains largely unclear. In ESCs, the reprogramming process goes through two critical stages: germline and zygotic demethylation, both of which erase genomic DNA methylation sites and hence allow for different gene expression patterns to be reset into a pluripotent state. Recently, miR-302, an ESC-specific microRNA (miRNA), was found to play an essential role in four aspects of this reprogramming mechanism-(1) initiating global genomic DNA demethylation, (2) activating ESC-specific gene expression, (3) inhibiting developmental signaling, and (4) preventing stem cell tumorigenicity. In this review, we will summarize miR-302 functions in all four reprogramming aspects and further discuss how these findings may improve the efficiency and safety of the current iPSC technology.

  8. The ROSA26-iPSC Mouse: A Conditional, Inducible, and Exchangeable Resource for Studying Cellular (DeDifferentiation

    Directory of Open Access Journals (Sweden)

    Lieven Haenebalcke

    2013-02-01

    Full Text Available Control of cellular (dedifferentiation in a temporal, cell-specific, and exchangeable manner is of paramount importance in the field of reprogramming. Here, we have generated and characterized a mouse strain that allows iPSC generation through the Cre/loxP conditional and doxycycline/rtTA-controlled inducible expression of the OSKM reprogramming factors entirely from within the ROSA26 locus. After reprogramming, these factors can be replaced by genes of interest—for example, to enhance lineage-directed differentiation—with the use of a trap-coupled RMCE reaction. We show that, similar to ESCs, Dox-controlled expression of the cardiac transcriptional regulator Mesp1 together with Wnt inhibition enhances the generation of functional cardiomyocytes upon in vitro differentiation of such RMCE-retargeted iPSCs. This ROSA26-iPSC mouse model is therefore an excellent tool for studying both cellular reprogramming and lineage-directed differentiation factors from the same locus and will greatly facilitate the identification and ease of functional characterization of the genetic/epigenetic determinants involved in these complex processes.

  9. Distinct and Shared Determinants of Cardiomyocyte Contractility in Multi-Lineage Competent Ethnically Diverse Human iPSCs.

    Science.gov (United States)

    Tomov, Martin L; Olmsted, Zachary T; Dogan, Haluk; Gongorurler, Eda; Tsompana, Maria; Otu, Hasan H; Buck, Michael; Chang, Eun-Ah; Cibelli, Jose; Paluh, Janet L

    2016-12-05

    The realization of personalized medicine through human induced pluripotent stem cell (iPSC) technology can be advanced by transcriptomics, epigenomics, and bioinformatics that inform on genetic pathways directing tissue development and function. When possible, population diversity should be included in new studies as resources become available. Previously we derived replicate iPSC lines of African American, Hispanic-Latino and Asian self-designated ethnically diverse (ED) origins with normal karyotype, verified teratoma formation, pluripotency biomarkers, and tri-lineage in vitro commitment. Here we perform bioinformatics of RNA-Seq and ChIP-seq pluripotency data sets for two replicate Asian and Hispanic-Latino ED-iPSC lines that reveal differences in generation of contractile cardiomyocytes but similar and robust differentiation to multiple neural, pancreatic, and smooth muscle cell types. We identify shared and distinct genes and contributing pathways in the replicate ED-iPSC lines to enhance our ability to understand how reprogramming to iPSC impacts genes and pathways contributing to cardiomyocyte contractility potential.

  10. In situ genetic correction of F8 intron 22 inversion in hemophilia A patient-specific iPSCs.

    Science.gov (United States)

    Wu, Yong; Hu, Zhiqing; Li, Zhuo; Pang, Jialun; Feng, Mai; Hu, Xuyun; Wang, Xiaolin; Lin-Peng, Siyuan; Liu, Bo; Chen, Fangping; Wu, Lingqian; Liang, Desheng

    2016-01-08

    Nearly half of severe Hemophilia A (HA) cases are caused by F8 intron 22 inversion (Inv22). This 0.6-Mb inversion splits the 186-kb F8 into two parts with opposite transcription directions. The inverted 5' part (141 kb) preserves the first 22 exons that are driven by the intrinsic F8 promoter, leading to a truncated F8 transcript due to the lack of the last 627 bp coding sequence of exons 23-26. Here we describe an in situ genetic correction of Inv22 in patient-specific induced pluripotent stem cells (iPSCs). By using TALENs, the 627 bp sequence plus a polyA signal was precisely targeted at the junction of exon 22 and intron 22 via homologous recombination (HR) with high targeting efficiencies of 62.5% and 52.9%. The gene-corrected iPSCs retained a normal karyotype following removal of drug selection cassette using a Cre-LoxP system. Importantly, both F8 transcription and FVIII secretion were rescued in the candidate cell types for HA gene therapy including endothelial cells (ECs) and mesenchymal stem cells (MSCs) derived from the gene-corrected iPSCs. This is the first report of an efficient in situ genetic correction of the large inversion mutation using a strategy of targeted gene addition.

  11. 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.

  12. Integration-free reprogramming of human somatic cells to induced pluripotent stem cells (iPSCs) without viral vectors, recombinant DNA, and genetic modification.

    Science.gov (United States)

    Heng, Boon Chin; Fussenegger, Martin

    2014-01-01

    Stem cells are envisaged to be integral components of multicellular systems engineered for therapeutic applications. The reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) via recombinant expression of a limited number of transcription factors, which was first achieved by Yamanaka and colleagues in 2007, heralded a major breakthrough in the stem cell field. Since then, there has been rapid progress in the field of iPSC generation, including the identification of various small molecules that can enhance reprogramming efficiency and reduce the number of different transcription factors required for reprogramming. Nevertheless, the major obstacles facing clinical applications of iPSCs are safety concerns associated with the use of viral vectors and recombinant DNA for expressing the appropriate transcription factors during reprogramming. In particular, permanent genetic modifications to newly reprogrammed iPSCs have to be avoided in order to meet stringent safety requirements for clinical therapy. These safety challenges can be overcome by new technology platforms that enable cellular reprogramming to iPSCs without the need to utilize either recombinant DNA or viral vectors. The use of recombinant cell-penetrating peptides and direct transfection of synthetic mRNA encoding appropriate transcription factors have both been shown to successfully reprogram somatic cells to iPSCs. It has also been shown more recently that the direct transfection of certain miRNA species can reprogram somatic cells to pluripotency without the need for any of the transcription factors commonly utilized for iPSC generation. This chapter describes protocols for iPSC generation with these new techniques, which would obviate the use of recombinant DNA and viral vectors in cellular reprogramming, thus avoiding permanent genetic modification to the reprogrammed cells.

  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. 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.

  15. A Laser Interferometric Miniature Sensor

    Energy Technology Data Exchange (ETDEWEB)

    Carr, Dustin W., PhD.; Baldwin, Patrick C.; Milburn, Howard; Robinson, David

    2011-09-12

    This is the second year of a Phase II Small Business Innovation Research (SBIR) contract geared towards the development of a new seismic sensor. Ground-based seismic monitoring systems have proven to be very capable in identifying nuclear tests, and can provide somewhat precise information on the location and yield of the explosive device. Making these measurements, however, currently requires very expensive and bulky seismometers that are difficult to deploy in places where they are most needed. A high performance, compact device can enable rapid deployment of large scale arrays, which can in turn be used to provide higher quality data during times of critical need. The use of a laser interferometer-based device has shown considerable promise, while also presenting significant challenges. The greatest strength of this optical readout technique is the ability to decouple the mechanical design from the transducer, thus enabling a miniaturized design that is not accessible with conventional sensing techniques. However, the nonlinearity in the optical response must be accounted for in the sensor output. Previously, we had proposed using a force-feedback approach to position the sensor at a point of maximum linearity. However, it can be shown that the combined nonlinearities of the optical response and the force-feedback curve necessarily results in a significant amount of unwanted noise at low frequencies. Having realized this, we have developed a new approach that eliminates force feedback, allowing the proof mass to move freely at all times. This takes advantage of some advanced optical spatial filtering that was developed at Symphony Acoustics for other types of sensors, and was recently adapted to this work. After processing the signals in real time, the digital output of the device is intrinsically linear, and the sensor can operate at any orientation with the same level of resolution, while instantly adapting to significant changes in orientation. Ultimately, we

  16. Towards optimisation of induced pluripotent cell culture: Extracellular acidification results in growth arrest of iPSC prior to nutrient exhaustion.

    Science.gov (United States)

    Wilmes, Anja; Rauch, Caroline; Carta, Giada; Kern, Georg; Meier, Florian; Posch, Wilfried; Wilflingseder, Doris; Armstrong, Lyle; Lako, Majlinda; Beilmann, Mario; Gstraunthaler, Gerhard; Jennings, Paul

    2017-12-01

    Human induced pluripotent stem cells (iPSC) have the potential to radically reduce the number of animals used in both toxicological science and disease elucidation. One initial obstacle culturing iPSC is that they require daily medium exchange. This study attempts to clarify why and propose some practical solutions. Two iPSC lineages were fed at different intervals in a full growth area (FGA) or a restricted growth area (RGA). The FGA consisted of a well coated with Matrigel™ and the RGA consisted of a coated coverslip placed in a well. Glucose, lactate, extracellular pH and cell cycle phases were quantified. Without daily feeding, FGA cultured iPSC had significantly reduced growth rates by day 2 and began to die by day 3. In contrast, RGA cultured cells grew to confluence over 3days. Surprisingly, glucose was not exhausted under any condition. However, extracellular pH reached 6.8 after 72h in FGA cultures. Artificially reducing medium pH to 6.8 also inhibited glycolysis and initiated an increase in G0/G1 phase of the cell cycle, while adding an additional 10mM bicarbonate to the medium increased glycolysis rates. This study demonstrates that iPSC are highly sensitive to extracellular acidification, a likely limiting factor in maintenance of proliferative and pluripotent status. Culturing iPSC in RGA prevents rapid extracellular acidification, while still maintaining pluripotency and allowing longer feeding cycles. Copyright © 2017. Published by Elsevier Ltd.

  17. 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.

  18. 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.

  19. Design and fabrication of miniature combination lock

    International Nuclear Information System (INIS)

    Yang Gao; Wei Su

    2006-01-01

    Design and fabrication of a miniature combination lock is reported. The prototype's outline size is less than 15mm x 20mm x 25mm, with the function of 24 steps single-try discrimination. Two miniature application-specific electromagnetic motors are used to drive a counter meshing gears (CMG) mechanism. Ratchet-pawl mechanism is respectively attached to each CMG gears assembly, to insure it step forward at accurate angles in company with motor driving circuit. Main functional components of the lock are fabricated by UV-LIGA micromachining process, including the motor's stator with 4-level planar coils. Handcraft assembling process and control circuit design are also briefly introduced. The prototype had already endured more than 1000 times of unlocking and 100 times of manually unlocking. It is proved that micro-motor and micromachining technologies are very useful in miniaturization of such a surety device

  20. Batch fabrication of precision miniature permanent magnets

    Science.gov (United States)

    Christenson, Todd R.; Garino, Terry J.; Venturini, Eugene L.

    2002-01-01

    A new class of processes for fabrication of precision miniature rare earth permanent magnets is disclosed. Such magnets typically have sizes in the range 0.1 to 10 millimeters, and dimensional tolerances as small as one micron. Very large magnetic fields can be produced by such magnets, lending to their potential application in MEMS and related electromechanical applications, and in miniature millimeter-wave vacuum tubes. This abstract contains simplifications, and is supplied only for purposes of searching, not to limit or alter the scope or meaning of any claims herein.

  1. Spontaneous uterine rupture

    African Journals Online (AJOL)

    ABSTRACT. Rupture of a gravid uterus is a surgical emergency. Predisposing factors include a scarred uterus. Spontaneous rupture of an unscarred uterus during pregnancy is a rare occurrence. We hereby present the case of a spontaneous complete uterine rupture at a gestational age of 34 weeks in a 35 year old patient ...

  2. 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.

  3. Adventitious shoot regeneration from leaf explants of miniature paprika

    African Journals Online (AJOL)

    STORAGESEVER

    2010-05-10

    May 10, 2010 ... A simple and efficient protocol was developed for in vitro propagation of two miniature paprika cultivars. Seeds of miniature paprika ... cultivars against bacteria, fungi, virus and pest. Plant regeneration via ... Plant materials, culture media and experimental conditions. Seeds of miniature paprikas (C.

  4. Two Views of Islam: Ceramic Tile Design and Miniatures.

    Science.gov (United States)

    Macaulay, Sara Grove

    2001-01-01

    Describes an art project focusing on Islamic art that consists of two parts: (1) ceramic tile design; and (2) Islamic miniatures. Provides background information on Islamic art and step-by-step instructions for designing the Islamic tile and miniature. Includes learning objectives and resources on Islamic tile miniatures. (CMK)

  5. Miniaturized Planar Split-Ring Resonator Antenna

    DEFF Research Database (Denmark)

    Kim, Oleksiy S.; Breinbjerg, Olav

    2009-01-01

    A miniaturized planar antenna based on a broadside-coupled split ring resonator excited by an arc-shaped dipole is presented. The excitation dipole acts as a small tuning capacitor in series with a parallel RLC circuit represented by the SRR. The antenna resonance frequency and dimensions...

  6. 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

  7. Antenna Miniaturization with MEMS Tunable Capacitors

    DEFF Research Database (Denmark)

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

    2014-01-01

    and their characteristics are used in this investigation. This paper uses field simulations to highlight the trade-offs between the design of the tuner and the design of the antenna, especially the impact of the location of the tuner and the degree of miniaturization. Co-designing the tuner and the antenna is essential...

  8. 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...

  9. 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…

  10. MODIFIED EDGE FED SIERPINSKI CARPET MINIATURIZED ...

    African Journals Online (AJOL)

    This paper presented a modified edge fed Sierpinski carpet microstrip patch antenna for antenna miniaturization. The proposed design was etched as Sierpinski carpet to lower the antenna resonant frequency, which is used to reduce the conventional patch antenna size. After the Sierpinski carpet second iteration, the ...

  11. Miniature Paintings: Small Size, Big Impact!

    Science.gov (United States)

    Hicks, Bill

    2011-01-01

    This article describes a miniature painting project that allows students to research a master painter and then replicate the work on a smaller scale. This lesson focuses on the students' ability to learn to identify style, subject matter, themes, and content in painting through the study of historical paintings, and the application of various…

  12. 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.

  13. 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.

  14. 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.

  15. Generation of Hermansky–Pudlak Syndrome Type 1 (HPS1 induced pluripotent stem cells (iPSCs

    Directory of Open Access Journals (Sweden)

    Jean Ann Maguire

    2016-03-01

    Full Text Available Hermansky–Pudlak syndrome (HPS is a rare autosomal recessive disorder characterized by deficiencies in lysosome-related organelles such as melanosomes and platelet-dense granules. The disorder is classified into nine different subtypes (HPS1–HPS9 based on genetic mutations in 9 unique genes. Here we describe the generation of an HPS1 iPSC line (CHOPHPS1 using a Cre-excisable polycistronic STEMCCA lentivirus. This line was derived from human fibroblasts isolated from a patient carrying a duplicative mutation in the HPS1 gene. The patient presented with oculocutaneous albinism, early pulmonary fibrosis, and hemorrhagic diathesis.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. 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.

  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. Miniature Heat Transport System for Nanosatellite Technology

    Science.gov (United States)

    Douglas, Donya M,

    1999-01-01

    The scientific understanding of key physical processes between the Sun and the Earth require simultaneous measurements from many vantage points in space. Nano-satellite technologies will enable a class of constellation missions for the NASA Space Science Sun-Earth Connections. This recent emphasis on the implementation of smaller satellites leads to a requirement for development of smaller subsystems in several areas. Key technologies under development include: advanced miniaturized chemical propulsion; miniaturized sensors; highly integrated, compact electronics; autonomous onboard and ground operations; miniatures low power tracking techniques for orbit determination; onboard RF communications capable of transmitting data to the ground from far distances; lightweight efficient solar array panels; lightweight, high output battery cells; lightweight yet strong composite materials for the nano-spacecraft and deployer-ship structures. These newer smaller systems may have higher power densities and higher thermal transport requirements than seen on previous small satellites. Furthermore, the small satellites may also have a requirement to maintain thermal control through extended earth shadows, possibly up to 8 hours long. Older thermal control technology, such as heaters, thermostats, and heat pipes, may not be sufficient to meet the requirements of these new systems. Conversely, a miniature two-phase heat transport system (Mini-HTS) such as a Capillary Pumped Loop (CPL) or Loop Heat Pipe (LBP) is a viable alternative. A Mini-HTS can provide fine temperature control, thermal diode action, and a highly efficient means of heat transfer. The Mini-HTS would have power capabilities in the range of tens of watts or less and provide thermal control over typical spacecraft ranges. The Mini-HTS would allow the internal portion of the spacecraft to be thermally isolated from the external radiator, thus protecting the internal components from extreme cold temperatures during an

  1. Myelogenous leukemia in adult inbred MHC-defined miniature swine: a model for human myeloid leukemias.

    Science.gov (United States)

    Duran-Struuck, Raimon; Cho, Patricia S; Teague, Alexander G S; Fishman, Brian; Fishman, Aaron S; Hanekamp, John S; Moran, Shannon G; Wikiel, Krzysztof J; Ferguson, Kelly K; Lo, Diana P; Duggan, Michael; Arn, J Scott; Billiter, Bob; Horner, Ben; Houser, Stuart; Yeap, Beow Yong; Westmoreland, Susan V; Spitzer, Thomas R; McMorrow, Isabel M; Sachs, David H; Bronson, Roderick T; Huang, Christene A

    2010-06-15

    This manuscript reports on five cases of spontaneous myelogenous leukemia, similar to human disease, occurring within highly inbred, histocompatible sublines of Massachusetts General Hospital (MGH) MHC-defined miniature swine. In cases where a neoplasm was suspected based on clinical observations, samples were obtained for complete blood count, peripheral blood smear, and flow cytometric analysis. Animals confirmed to have neoplasms were euthanized and underwent necropsy. Histological samples were obtained from abnormal tissues and suspect lesions. The phenotype of the malignancies was assessed by flow cytometric analysis of processed peripheral blood mononuclear cells and affected tissues. Five cases of spontaneous myeloid leukemia were identified in adult animals older than 30 months of age. All animals presented with symptoms of weight loss, lethargy, and marked leukocytosis. At autopsy, all animals had systemic disease involvement and presented with severe hepatosplenomegaly. Three of the five myelogenous leukemias have successfully been expanded in vitro. The clustered incidence of disease in this closed herd suggests that genetic factors may be contributing to disease development. Myelogenous leukemia cell lines established from inbred sublines of MGH MHC-defined miniature swine have the potential to be utilized as a model to evaluate therapies of human leukemia. Copyright 2009 Elsevier B.V. All rights reserved.

  2. Miniature synthetic-aperture radar system

    Science.gov (United States)

    Stockton, Wayne; Stromfors, Richard D.

    1990-11-01

    Loral Defense Systems-Arizona has developed a high-performance synthetic-aperture radar (SAR) for small aircraft and unmanned aerial vehicle (UAV) reconnaissance applications. This miniature radar, called Miniature Synthetic-Aperture Radar (MSAR), is packaged in a small volume and has low weight. It retains key features of large SAR systems, including high-resolution imaging and all-weather operation. The operating frequency of MSAR can optionally be selected to provide foliage penetration capability. Many imaging radar configurations can be derived using this baseline system. MSAR with a data link provides an attractive UAV sensor. MSAR with a real-time image formation processor is well suited to installations where onboard processing and immediate image analysis are required. The MSAR system provides high-resolution imaging for short-to-medium range reconnaissance applications.

  3. 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

  4. Miniature Cavity-Enhanced Diamond Magnetometer

    Science.gov (United States)

    Chatzidrosos, Georgios; Wickenbrock, Arne; Bougas, Lykourgos; Leefer, Nathan; Wu, Teng; Jensen, Kasper; Dumeige, Yannick; Budker, Dmitry

    2017-10-01

    We present a highly sensitive miniaturized cavity-enhanced room-temperature magnetic-field sensor based on nitrogen-vacancy centers in diamond. The magnetic resonance signal is detected by probing absorption on the 1042-nm spin-singlet transition. To improve the absorptive signal the diamond is placed in an optical resonator. The device has a magnetic-field sensitivity of 28 pT /√{Hz } , a projected photon shot-noise-limited sensitivity of 22 pT /√{Hz } , and an estimated quantum projection-noise-limited sensitivity of 0.43 pT /√{Hz } with the sensing volume of ˜390 μ m ×4500 μ m2 . The presented miniaturized device is the basis for an endoscopic magnetic-field sensor for biomedical applications.

  5. Miniaturized Retrodirective Arrays for a Nanosatellite Platform

    Science.gov (United States)

    2012-01-01

    Miniaturized Retrodirective Arrays for a Nanosatellite Platform NIA Sb. GRANT NUMBER N00014-1 0-1-0056 Sc. PROGRAM ELEMENT NUMBER . NIA 6. AUTHOR(S) Sd...into a mobile platfonn, such as a nanosatellite , presents unique challenges due to the platform’s restrictions in terms of size, weight, and power...of power detection and null scanning. 1S. SUBJECT TERMS Retrodirective Array, Nanosatellite 16. SECURITY CLASSIFICATION OF: a. REPORT b. ABSTRACT

  6. 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.)

  7. Miniature thermoelectric coolers for semiconductor lasers

    International Nuclear Information System (INIS)

    Semenyuk, V.A.; Pilipenko, T.V.; Albright, G.C.; Ioffe, L.A.; Rolls, W.H.

    1994-01-01

    The problem of matching thermoelectric coolers and semiconductor lasers with respect to heat flow densities and electrical currents is discussed. It is shown that the solution of this problem is accomplished by the reduction of thermoelement dimensions to the submillimeter level. Assembled with extruded thermoelectric materials, miniature coolers with a thermoelement length as short as 0.1 mm and a cross section of 0.2x0.2 mm 2 are demonstrated. Using 0.5 mm thick aluminum ceramic plates, the overall height of these miniature coolers can be as low as 1.1 mm. The devices are designed for cooling and thermally stabilizing miniature optoelectronic elements, especially semiconductor lasers. The results of device testing over a wide range of temperature and heat loads are given. This novel approach in thermoelectric cooler design represents a new step in miniaturization and reduced current requirements, with little or no loss in maximum attainable temperature difference. A ΔT max of 68 K is demonstrated with input current of 200 mA. Due to the small thermoelement length, extremely large heat flow densities at cold junctions are practical (up to 100 W/cm 2 at ΔT=0), making these devices ideal for heat intensive local sources such as injection laser diodes. Due to the extremely small sizes, these coolers have a high speed of response where a ΔT of 35 K in specimens with the thermoelement length of 0.1 mm is approximately 150 milliseconds. These micro coolers are ideal for use within the semiconductor device housing and under conditions where limitations of power, size, and electrical current predominate. copyright 1995 American Institute of Physics

  8. DNA methylation alterations in iPSC- and hESC-derived neurons: potential implications for neurological disease modeling.

    Science.gov (United States)

    de Boni, Laura; Gasparoni, Gilles; Haubenreich, Carolin; Tierling, Sascha; Schmitt, Ina; Peitz, Michael; Koch, Philipp; Walter, Jörn; Wüllner, Ullrich; Brüstle, Oliver

    2018-01-01

    Genetic predisposition and epigenetic alterations are both considered to contribute to sporadic neurodegenerative diseases (NDDs) such as Parkinson's disease (PD). Since cell reprogramming and the generation of induced pluripotent stem cells (iPSCs) are themselves associated with major epigenetic remodeling, it remains unclear to what extent iPSC-derived neurons lend themselves to model epigenetic disease-associated changes. A key question to be addressed in this context is whether iPSC-derived neurons exhibit epigenetic signatures typically observed in neurons derived from non-reprogrammed human embryonic stem cells (hESCs). Here, we compare mature neurons derived from hESC and isogenic human iPSC generated from hESC-derived neural stem cells. Genome-wide 450 K-based DNA methylation and HT12v4 gene array expression analyses were complemented by a deep analysis of selected genes known to be involved in NDD. Our studies show that DNA methylation and gene expression patterns of isogenic hESC- and iPSC-derived neurons are markedly preserved on a genome-wide and single gene level. Overall, iPSC-derived neurons exhibit similar DNA methylation patterns compared to isogenic hESC-derived neurons. Further studies will be required to explore whether the epigenetic patterns observed in iPSC-derived neurons correspond to those detectable in native brain neurons.

  9. Genes Associated with Pancreas Development and Function Maintain Open Chromatin in iPSCs Generated from Human Pancreatic Beta Cells

    Directory of Open Access Journals (Sweden)

    Matthias Thurner

    2017-11-01

    Full Text Available Current in vitro islet differentiation protocols suffer from heterogeneity and low efficiency. Induced pluripotent stem cells (iPSCs derived from pancreatic beta cells (BiPSCs preferentially differentiate toward endocrine pancreas-like cells versus those from fibroblasts (FiPSCs. We interrogated genome-wide open chromatin in BiPSCs and FiPSCs via ATAC-seq and identified ∼8.3k significant, differential open chromatin sites (DOCS between the two iPSC subtypes (false discovery rate [FDR] < 0.05. DOCS where chromatin was more accessible in BiPSCs (Bi-DOCS were significantly enriched for known regulators of endodermal development, including bivalent and weak enhancers, and FOXA2 binding sites (FDR < 0.05. Bi-DOCS were associated with genes related to pancreas development and beta-cell function, including transcription factors mutated in monogenic diabetes (PDX1, NKX2-2, HNF1A; FDR < 0.05. Moreover, Bi-DOCS correlated with enhanced gene expression in BiPSC-derived definitive endoderm and pancreatic progenitor cells. Bi-DOCS therefore highlight genes and pathways governing islet-lineage commitment, which can be exploited for differentiation protocol optimization, diabetes disease modeling, and therapeutic purposes.

  10. An iPSC Line from Human Pancreatic Ductal Adenocarcinoma Undergoes Early to Invasive Stages of Pancreatic Cancer Progression

    Directory of Open Access Journals (Sweden)

    Jungsun Kim

    2013-06-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC carries a dismal prognosis and lacks a human cell model of early disease progression. When human PDAC cells are injected into immunodeficient mice, they generate advanced-stage cancer. We hypothesized that if human PDAC cells were converted to pluripotency and then allowed to differentiate back into pancreatic tissue, they might undergo early stages of cancer. Although most induced pluripotent stem cell (iPSC lines were not of the expected cancer genotype, one PDAC line, 10–22 cells, when injected into immunodeficient mice, generated pancreatic intraepithelial neoplasia (PanIN precursors to PDAC that progressed to the invasive stage. The PanIN-like cells secrete or release proteins from many genes that are known to be expressed in human pancreatic cancer progression and that predicted an HNF4α network in intermediate-stage lesions. Thus, rare events allow iPSC technology to provide a live human cell model of early pancreatic cancer and insights into disease progression.

  11. Culture of iPSCs Derived Pancreatic β-Like Cells In Vitro Using Decellularized Pancreatic Scaffolds: A Preliminary Trial

    Directory of Open Access Journals (Sweden)

    Jian Wan

    2017-01-01

    Full Text Available Diabetes mellitus is a disease which has affected 415 million patients in 2015. In an effort to replace the significant demands on transplantation and morbidity associated with transplantation, the production of β-like cells differentiated from induced pluripotent stem cells (iPSCs was evaluated. This approach is associated with promising decellularized scaffolds with natural extracellular matrix (ECM and ideal cubic environment that will promote cell growth in vivo. Our efforts focused on combining decellularized rat pancreatic scaffolds with mouse GFP+-iPSCs-derived pancreatic β-like cells, to evaluate whether decellularized scaffolds could facilitate the growth and function of β-like cells. β-like cells were differentiated from GFP+-iPSCs and evaluated via cultivating in the dynamic circulation perfusion device. Our results demonstrated that decellularized pancreatic scaffolds display favorable biochemical properties. Furthermore, not only could the scaffolds support the survival of β-like cells, but they also accelerated the expression of the insulin as compared to plate-based cell culture. In conclusion, these results suggest that decellularized pancreatic scaffolds could provide a suitable platform for cellular activities of β-like cells including survival and insulin secretion. This study provides preliminary support for regenerating insulin-secreting organs from the decellularized scaffolds combined with iPSCs derived β-like cells as a potential clinical application.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  14. 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.

  15. Generation of induced pluripotent stem cell (iPSC line from a 21-year-old X-linked adrenoleukodystrophy (X-ALD patient

    Directory of Open Access Journals (Sweden)

    Young Rang You

    2017-12-01

    Full Text Available X-linked Adrenoleukodystrophy (X-ALD is a genetic disease that caused by mutations in adenosine triphosphate [ATP]-binding-cassette transporter superfamily D member 1 (ABCD1 gene. We generated an induced pluripotent stem cell (iPSC line from a 21-year-old male X-ALD patient-derived fibroblasts by Sendai virus mediated reprogramming. Established iPSCs stably expanded while maintaining immunoreactivity for various pluripotency markers and alkaline phosphatase, as well as normal 44 + XY karyotype. Under the differentiation condition, the cells gave rise to cells of three germ layers.

  16. Generation of two induced pluripotent stem cell (iPSC lines from X-linked adrenoleukodystrophy (X-ALD patients with adrenomyeloneuropathy (AMN

    Directory of Open Access Journals (Sweden)

    Daryeon Son

    2017-12-01

    Full Text Available X-linked adrenoleukodystrophy (X-ALD is an inherited disorder caused by a mutation in the ATP-binding cassette transporter subfamily D member 1 (ABCD1 gene. We generated two induced pluripotent stem cell (iPSC lines from X-ALD patients with adrenomyeloneuropathy (AMN by Sendai virus containing OCT4, SOX2, KLF4 and c-MYC. Established iPSC lines expressed various pluripotency markers, had differentiation potential of three germ layers in vitro, had normal karyotype and retained ABCD1 mutation.

  17. Generation and characterization of a human iPSC line from a patient with propionic acidemia due to defects in the PCCA gene

    Directory of Open Access Journals (Sweden)

    Esmeralda Alonso-Barroso

    2017-08-01

    Full Text Available Human induced pluripotent stem cell (iPSC line was generated from fibroblasts of a patient with propionic acidemia carrying mutations in the PCCA gene: c.1899+4_1899+7delAGTA; p.(Cys616_Val633del and c.1430−−?_1643+?del; p.(Gly477Glufs*9. Reprogramming factors OCT3/4, SOX2, KLF4 and c-MYC were delivered using a non-integrative method based on the Sendai virus. Once established, iPSCs have shown full pluripotency, differentiation capacity and genetic stability.

  18. Generation and characterization of a human iPSC line from a patient with propionic acidemia due to defects in the PCCA gene.

    Science.gov (United States)

    Alonso-Barroso, Esmeralda; Brasil, Sandra; Briso-Montiano, Álvaro; Navarrete, Rosa; Pérez-Cerdá, Celia; Ugarte, Magdalena; Pérez, Belén; Desviat, Lourdes R; Richard, Eva

    2017-08-01

    Human induced pluripotent stem cell (iPSC) line was generated from fibroblasts of a patient with propionic acidemia carrying mutations in the PCCA gene: c.1899+4_1899+7delAGTA; p.(Cys616_Val633del) and c.1430--?_1643+?del; p.(Gly477Glufs*9). Reprogramming factors OCT3/4, SOX2, KLF4 and c-MYC were delivered using a non-integrative method based on the Sendai virus. Once established, iPSCs have shown full pluripotency, differentiation capacity and genetic stability. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. 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......, 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...

  20. Spontaneous Atraumatic Mediastinal Hemorrhage

    Directory of Open Access Journals (Sweden)

    Morkos Iskander BSc, BMBS, MRCS, PGCertMedEd

    2013-04-01

    Full Text Available Spontaneous atraumatic mediastinal hematomas are rare. We present a case of a previously fit and well middle-aged lady who presented with acute breathlessness and an increasing neck swelling and spontaneous neck bruising. On plain chest radiograph, widening of the mediastinum was noted. The bruising was later confirmed to be secondary to mediastinal hematoma. This life-threatening diagnostic conundrum was managed conservatively with a multidisciplinary team approach involving upper gastrointestinal and thoracic surgeons, gastroenterologists, radiologists, intensivists, and hematologists along with a variety of diagnostic modalities. A review of literature is also presented to help surgeons manage such challenging and complicated cases.

  1. 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.

  2. Conformal Ultracapacitor Power Source Technology for the Miniature Kill Vehicle

    National Research Council Canada - National Science Library

    2004-01-01

    .... The conformal ultracapacitor power source will be attached to the inside available surface of the individual miniature kill vehicle, The ultracapacitor will be charged through a charging system...

  3. Spontaneous Appendicocutaneous Fistula I

    African Journals Online (AJOL)

    M T0k0de* MB, BS and. Dr 0. A. AWOj0bi+ FMCS (Nig). ABSTRACT. Ruptured appendicitis is not a common cause of spontaneous enterocutaneous fistula. A case of ruptured retrocaecal appendicitis presenting as an enterocutaneous fistula in a Nigerian woman is presented. The literature on this disorder is also reviewed.

  4. [Spontaneous bacterial peritonitis].

    Science.gov (United States)

    Strauss, Edna; Caly, Wanda Regina

    2003-01-01

    Spontaneous bacterial peritonitis occurs in 30% of patients with ascites due to cirrhosis leading to high morbidity and mortality rates. The pathogenesis of spontaneous bacterial peritonitis is related to altered host defenses observed in end-stage liver disease, overgrowth of microorganisms, and bacterial translocation from the intestinal lumen to mesenteric lymph nodes. Clinical manifestations vary from severe to slight or absent, demanding analysis of the ascitic fluid. The diagnosis is confirmed by a number of neutrophils over 250/mm3 associated or not to bacterial growth in culture of an ascites sample. Enterobacteriae prevail and Escherichia coli has been the most frequent bacterium reported. Mortality rates decreased markedly in the last two decades due to early diagnosis and prompt antibiotic treatment. Third generation intravenous cephalosporins are effective in 70% to 95% of the cases. Recurrence of spontaneous bacterial peritonitis is common and can be prevented by the continuous use of oral norfloxacin. The development of bacterial resistance demands the search for new options in the prophylaxis of spontaneous bacterial peritonitis; probiotics are a promising new approach, but deserve further evaluation. Short-term antibiotic prophylaxis is recommended for patients with cirrhosis and ascites shortly after an acute episode of gastrointestinal bleeding.

  5. Spontaneous Grammar Explanations.

    Science.gov (United States)

    Tjoo, Hong Sing; Lewis, Marilyn

    1998-01-01

    Describes one New Zealand university language teacher's reflection on her own grammar explanations to university-level students of Bahasa Indonesian. Examines form-focused instruction through the teacher's spontaneous answers to students' questions about the form of the language they are studying. The teacher's experiences show that it takes time…

  6. EDITORIAL SPONTANEOUS BACTERIAL PERITONITIS ...

    African Journals Online (AJOL)

    hi-tech

    Spontaneous bacterial peritonitis (SBP) frequent]y occurs in patients with liver cirrhosis and ascites. It is defined as an infection of previously sterile ascitic fluid without any demonstrable intrabdominal source of infection. It is now internationally agreed that a polymorphonuclear (PMN) cell count in the ascitic fluid of over 250 ...

  7. Spontaneous dimensional reduction?

    Science.gov (United States)

    Carlip, Steven

    2012-10-01

    Over the past few years, evidence has begun to accumulate suggesting that spacetime may undergo a "spontaneous dimensional reduction" to two dimensions near the Planck scale. I review some of this evidence, and discuss the (still very speculative) proposal that the underlying mechanism may be related to short-distance focusing of light rays by quantum fluctuations.

  8. 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

  9. Newly introduced sample preparation techniques: towards miniaturization.

    Science.gov (United States)

    Costa, Rosaria

    2014-01-01

    Sampling and sample preparation are of crucial importance in an analytical procedure, representing quite often a source of errors. The technique chosen for the isolation of analytes greatly affects the success of a chemical determination. On the other hand, growing concerns about environmental and human safety, along with the introduction of international regulations for quality control, have moved the interest of scientists towards specific needs. Newly introduced sample preparation techniques are challenged to meet new criteria: (i) miniaturization, (ii) higher sensitivity and selectivity, and (iii) automation. In this survey, the most recent techniques introduced in the field of sample preparation will be described and discussed, along with many examples of applications.

  10. 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).

  11. Differentiation of control and ALS mutant human iPSCs into functional skeletal muscle cells, a tool for the study of neuromuscolar diseases

    Directory of Open Access Journals (Sweden)

    Jessica Lenzi

    2016-07-01

    Full Text Available Amyotrophic Lateral Sclerosis (ALS is a severe and fatal neurodegenerative disease characterized by progressive loss of motoneurons, muscle atrophy and paralysis. Recent evidence suggests that ALS should be considered as a multi-systemic disease, in which several cell types contribute to motoneuron degeneration. In this view, mutations in ALS linked genes in other neural and non-neural cell types may exert non-cell autonomous effects on motoneuron survival and function. Induced Pluripotent Stem Cells (iPSCs have been recently derived from several patients with ALS mutations and it has been shown that they can generate motoneurons in vitro, providing a valuable tool to study ALS. However, the potential of iPSCs could be further valorized by generating other cell types that may be relevant to the pathology. In this paper, by taking advantage of a novel inducible system for MyoD expression, we show that both control iPSCs and iPSCs carrying mutations in ALS genes can generate skeletal muscle cells. We provide evidence that both control and mutant iPSC-derived myotubes are functionally active. This in vitro system will be instrumental to dissect the molecular and cellular pathways impairing the complex motoneuron microenvironment in ALS.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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...

  14. 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.

  15. 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.

  16. Induced pluripotent stem cells (iPSCs) derived from a patient with frontotemporal dementia caused by a P301L mutation in microtubule-associated protein tau (MAPT)

    DEFF Research Database (Denmark)

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

    2016-01-01

    SOX2, hKLF2, hL-MYC,hLIN-28 and shP53. iPSCs were free of genomically integrated reprogramming genes, contained the expected c.902C>T substitution in exon 10 of the MAPT gene, expressed the expected pluripotency markers, displayed in vitro differentiation potential to the three germ layers and had...

  17. 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, hL-MYC...

  18. 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...

  19. 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...

  20. 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.

  1. 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

  2. Creep test with use of miniaturized specimens

    Science.gov (United States)

    Chvostová, E.; Džugan, J.

    2017-02-01

    Application of the mini samples methods is very common especially for residual service life assessment of the components operating in the energy sector. Residual lifetime of operating device can be evaluated using standard tests, but these usually cannot be performed due to limited material amount that can be extracted from the components. It is possible to use in these cases a semi destructive sampling of materials and testing methods employing miniature specimens. This article deals with comparison of the creep results obtained with the use of on standard test bars and sub sized samples such as Small Punch Test and newly proposed miniature samples that are axially loaded. The experiment was performed on steam line steel CSN 15 128 after operation. Emphasis was put to practical use of the test results and therefore residual life was assessed with the use of standard and new mini specimens. The results obtained for standard and mini samples exhibit very good agreement without necessity of any correlation as in the case of SPT and thus much more straight forward approach can be applied even for “unknown materials”.

  3. Miniaturized optical neuroimaging in unrestrained animals.

    Science.gov (United States)

    Yu, Hang; Senarathna, Janaka; Tyler, Betty M; Thakor, Nitish V; Pathak, Arvind P

    2015-06-01

    The confluence of technological advances in optics, miniaturized electronic components and the availability of ever increasing and affordable computational power have ushered in a new era in functional neuroimaging, namely, an era in which neuroimaging of cortical function in unrestrained and unanesthetized rodents has become a reality. Traditional optical neuroimaging required animals to be anesthetized and restrained. This greatly limited the kinds of experiments that could be performed in vivo. Now one can assess blood flow and oxygenation changes resulting from functional activity and image functional response in disease models such as stroke and seizure, and even conduct long-term imaging of tumor physiology, all without the confounding effects of anesthetics or animal restraints. These advances are shedding new light on mammalian brain organization and function, and helping to elucidate loss of this organization or 'dysfunction' in a wide array of central nervous system disease models. In this review, we highlight recent advances in the fabrication, characterization and application of miniaturized head-mounted optical neuroimaging systems pioneered by innovative investigators from a wide array of disciplines. We broadly classify these systems into those based on exogenous contrast agents, such as single- and two-photon microscopy systems; and those based on endogenous contrast mechanisms, such as multispectral or laser speckle contrast imaging systems. Finally, we conclude with a discussion of the strengths and weaknesses of these approaches along with a perspective on the future of this exciting new frontier in neuroimaging. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Spontaneous healing of spontaneous coronary artery dissection.

    Science.gov (United States)

    Almafragi, Amar; Convens, Carl; Heuvel, Paul Van Den

    2010-01-01

    Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome and sudden cardiac death. It should be suspected in every healthy young woman without cardiac risk factors, especially during the peripartum or postpartum periods. It is important to check for a history of drug abuse, collagen vascular disease or blunt trauma of the chest. Coronary angiography is essential for diagnosis and early management. We wonder whether thrombolysis might aggravate coronary dissection. All types of treatment (medical therapy, percutaneous intervention or surgery) improve the prognosis without affecting survival times if used appropriately according to the clinical stability and the angiographic features of the involved coronary arteries. Prompt recognition and targeted treatment improve outcomes. We report a case of SCAD in a young female free of traditional cardiovascular risk factors, who presented six hours after thrombolysis for ST elevation myocardial infarction. Coronary angiography showed a dissection of the left anterior descending and immediate branch. She had successful coronary artery bypass grafting, with complete healing of left anterior descending dissection.

  5. Spontaneous spinal epidural abscess.

    LENUS (Irish Health Repository)

    Ellanti, P

    2011-10-01

    Spinal epidural abscess is an uncommon entity, the frequency of which is increasing. They occur spontaneously or as a complication of intervention. The classical triad of fever, back pain and neurological symptoms are not always present. High index of suspicion is key to diagnosis. Any delay in diagnosis and treatment can have significant neurological consequences. We present the case of a previously well man with a one month history of back pain resulting from an epidural abscess.

  6. Characterization of a novel miniature cell culture device

    Science.gov (United States)

    Moore, Sandra K.; Kleis, Stanley J.

    2008-05-01

    Recent advancements in the field of microfluidics have generated much interest in the advent of a miniaturized cell culture device. In this study, we developed a novel miniature culture system (cells, either prokaryotic or eukaryotic in type, for both 1 g and microgravity applications. The miniature culture system may advance the development of microanalytical remote monitoring tools such as biological sentinels, biosensors, and lab-on-a-chip. Integrating the autonomous miniature culture system with a microanalytical device makes a powerful biological tool. Cells can be cultured long-term, harvested, and released directly into an analytical tool without the need for human interaction through fluid dynamic manipulations. This work characterizes the miniature bioreactor system through numerical and experimental proof of concept studies.

  7. Miniature photovoltaic energy system for lighting

    International Nuclear Information System (INIS)

    Awais, M.

    1999-01-01

    In this project a miniature photovoltaic energy system has been designed and developed, that may be used in remote areas and villages for lighting purposes. System sizing is the important part of the project because it affects the cost of the system. Therefore, first of all system sizing has been done. For conversion of dc voltage of the battery into ac voltage, an inverter has been designed. To charge the battery when the sun is not shining, a standby system has been developed using a bicycle and dynamo. To indicate the battery's state of charge and discharge, a battery monitoring circuit has also been developed. Similarly, to protect the battery from over discharging, a battery protection circuit has been designed. In order to measure how much energy is going from standby system to the battery, an efficient dc electronic energy meter has been designed and developed. The working of the overall system has been tested and found to give good performance. (author)

  8. Self-folding miniature elastic electric devices

    International Nuclear Information System (INIS)

    Miyashita, Shuhei; Meeker, Laura; Rus, Daniela; Tolley, Michael T; Wood, Robert J

    2014-01-01

    Printing functional materials represents a considerable impact on the access to manufacturing technology. In this paper we present a methodology and validation of print-and-self-fold miniature electric devices. Polyvinyl chloride laminated sheets based on metalized polyester film show reliable self-folding processes under a heat application, and it configures 3D electric devices. We exemplify this technique by fabricating fundamental electric devices, namely a resistor, capacitor, and inductor. Namely, we show the development of a self-folded stretchable resistor, variable resistor, capacitive strain sensor, and an actuation mechanism consisting of a folded contractible solenoid coil. Because of their pre-defined kinematic design, these devices feature elasticity, making them suitable as sensors and actuators in flexible circuits. Finally, an RLC circuit obtained from the integration of developed devices is demonstrated, in which the coil based actuator is controlled by reading a capacitive strain sensor. (paper)

  9. Portable, miniaturized, fibre delivered, multimodal CARS exoscope.

    Science.gov (United States)

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

    2013-07-15

    We demonstrate for the first time, a portable multimodal coherent anti-Stokes Raman scattering microscope (exoscope) for minimally invasive in-vivo imaging of tissues. This device is based around a micro-electromechanical system scanning mirror and miniaturized optics with light delivery accomplished by a photonic crystal fibre. A single Ti:sapphire femtosecond pulsed laser is used as the light source to produce CARS, two photon excitation fluorescence and second harmonic generation images. The high resolution and distortion-free images obtained from various resolution and bio-samples, particularly in backward direction (epi) successfully demonstrate proof of concept, and pave the path towards future non or minimally-invasive in vivo imaging.

  10. Miniature Trailing Edge Effector for Aerodynamic Control

    Science.gov (United States)

    Lee, Hak-Tae (Inventor); Bieniawski, Stefan R. (Inventor); Kroo, Ilan M. (Inventor)

    2008-01-01

    Improved miniature trailing edge effectors for aerodynamic control are provided. Three types of devices having aerodynamic housings integrated to the trailing edge of an aerodynamic shape are presented, which vary in details of how the control surface can move. A bucket type device has a control surface which is the back part of a C-shaped member having two arms connected by the back section. The C-shaped section is attached to a housing at the ends of the arms, and is rotatable about an axis parallel to the wing trailing edge to provide up, down and neutral states. A flip-up type device has a control surface which rotates about an axis parallel to the wing trailing edge to provide up, down, neutral and brake states. A rotating type device has a control surface which rotates about an axis parallel to the chord line to provide up, down and neutral states.

  11. An automated miniature robotic vehicle inspection system

    International Nuclear Information System (INIS)

    Dobie, Gordon; Summan, Rahul; MacLeod, Charles; Pierce, Gareth; Galbraith, Walter

    2014-01-01

    A novel, autonomous reconfigurable robotic inspection system for quantitative NDE mapping is presented. The system consists of a fleet of wireless (802.11g) miniature robotic vehicles, each approximately 175 × 125 × 85 mm with magnetic wheels that enable them to inspect industrial structures such as storage tanks, chimneys and large diameter pipe work. The robots carry one of a number of payloads including a two channel MFL sensor, a 5 MHz dry coupled UT thickness wheel probe and a machine vision camera that images the surface. The system creates an NDE map of the structure overlaying results onto a 3D model in real time. The authors provide an overview of the robot design, data fusion algorithms (positioning and NDE) and visualization software

  12. An automated miniature robotic vehicle inspection system

    Energy Technology Data Exchange (ETDEWEB)

    Dobie, Gordon; Summan, Rahul; MacLeod, Charles; Pierce, Gareth; Galbraith, Walter [Centre for Ultrasonic Engineering, University of Strathclyde, 204 George Street, Glasgow, G1 1XW (United Kingdom)

    2014-02-18

    A novel, autonomous reconfigurable robotic inspection system for quantitative NDE mapping is presented. The system consists of a fleet of wireless (802.11g) miniature robotic vehicles, each approximately 175 × 125 × 85 mm with magnetic wheels that enable them to inspect industrial structures such as storage tanks, chimneys and large diameter pipe work. The robots carry one of a number of payloads including a two channel MFL sensor, a 5 MHz dry coupled UT thickness wheel probe and a machine vision camera that images the surface. The system creates an NDE map of the structure overlaying results onto a 3D model in real time. The authors provide an overview of the robot design, data fusion algorithms (positioning and NDE) and visualization software.

  13. Power Electronics for a Miniaturized Arcjet

    Science.gov (United States)

    Pinero, Luis R.; Bowers, Glen E.

    1997-01-01

    A 0.3 kW Power Processing Unit (PPU) was designed, tested on resistive loads, and then integrated with a miniaturized arcjet. The main goal of the design was to minimize size and mass while maintaining reasonable efficiency. In order to obtain the desired reductions in mass, simple topologies and control methods were considered. The PPU design incorporates a 50 kHz, current-mode-control, pulse-width-modulated (PWM), push-pull topology. An input voltage of 28 +/- 4V was chosen for compatibility with typical unregulated low voltage busses anticipated for smallsats. An efficiency of 0.90 under nominal operating conditions was obtained. The component mass of the PPU was 0.475 kg and could be improved by optimization of the output filter design. The estimated mass for a flight PPU based on this design is less than a kilogram.

  14. Characteristics of a miniature vacuum spark

    Science.gov (United States)

    Wong, C. S.; Ong, C. X.; Chin, O. H.; Lee, S.; Choi, P.

    1989-12-01

    The characteristics of a miniature vacuum spark device are investigated. It is powered by a 2-stage 50 kV Marx and operated without an external triggering source. Discharge initiation is effected by an electron beam produced by the Pseudospark effect behind the hollow cathode. For discharges performed in air at a pressure of below 10-2 mbar, intense X-ray is detected. Although this X-ray has been found to consist of predominantly the Fe-Kα line produced by the electron beam bombardment of the stainless steel anode, its high intensity, singly-pulsed short-duration temporal structure and nearly monochromatic spectrum make the present vacuum spark an ideal pulsed X-ray source for many applications. The device is also compact, low cost and easy to operate. As an example of its applications, the contact radiography of a living lizard has been obtained using this X-ray source.

  15. 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.

  16. A miniature high repetition rate shock tube

    Science.gov (United States)

    Tranter, R. S.; Lynch, P. T.

    2013-09-01

    A miniature high repetition rate shock tube with excellent reproducibility has been constructed to facilitate high temperature, high pressure, gas phase experiments at facilities such as synchrotron light sources where space is limited and many experiments need to be averaged to obtain adequate signal levels. The shock tube is designed to generate reaction conditions of T > 600 K, P < 100 bars at a cycle rate of up to 4 Hz. The design of the apparatus is discussed in detail, and data are presented to demonstrate that well-formed shock waves with predictable characteristics are created, repeatably. Two synchrotron-based experiments using this apparatus are also briefly described here, demonstrating the potential of the shock tube for research at synchrotron light sources.

  17. Miniaturized ASIC-based multichannel scaler instrument

    Science.gov (United States)

    Ericson, M. N.; Turner, G. W.; McMillan, D. E.; Hoffheins, B. S.; Todd, R. A.; Hiller, J. M.

    1994-08-01

    A miniaturized multichannel scaler instrument has been developed to address size and operational constraints for data acquisition in a portable laser-induced luminescence system. The multichannel scaling (MCS) function is implemented as a programmable application specific integrated circuit (ASIC) with standard interfaces for control and data acquisition. The instrument is microcontroller-based with sufficient computing power for data manipulation and algorithmic processing. The unit includes electronics for laser control and amplification and pulse height discrimination of PMT pulses. Modification of the instrument should allow use in nuclear, chemical, and spectroscopy-related applications including Mossbauer experiments (left bracket) 1,2 (right bracket). Interfaces are incorporated allowing both computer-controlled and stand-alone operation. Implementation of the MCS function as an ASIC and comparison with conventional implementations are discussed. Full characterization of the MCS is presented including differential non-linearity (DNL), bin dead time, and bandwidth measurements.

  18. Spontaneous Thigh Compartment Syndrome

    Directory of Open Access Journals (Sweden)

    Khan, Sameer K

    2011-02-01

    Full Text Available A young man presented with a painful and swollen thigh, without any history of trauma, illness, coagulopathic medication or recent exertional exercise. Preliminary imaging delineated a haematoma in the anterior thigh, without any fractures or muscle trauma. Emergent fasciotomies were performed. No pathology could be identified intra-operatively, or on follow-up imaging. A review of thigh compartment syndromes described in literature is presented in a table. Emergency physicians and traumatologists should be cognisant of spontaneous atraumatic presentations of thigh compartment syndrome, to ensure prompt referral and definitive management of this limb-threatening condition. [West J Emerg Med. 2011;12(1:134-138].

  19. 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.

  20. Spontaneous Tumor Lysis Syndrome

    Directory of Open Access Journals (Sweden)

    Alicia C. Weeks MD

    2015-08-01

    Full Text Available Tumor lysis syndrome (TLS is a known complication of malignancy and its treatment. The incidence varies on malignancy type, but is most common with hematologic neoplasms during cytotoxic treatment. Spontaneous TLS is thought to be rare. This case study is of a 62-year-old female admitted with multisystem organ failure, with subsequent diagnosis of aggressive B cell lymphoma. On admission, laboratory abnormalities included renal failure, elevated uric acid (20.7 mg/dL, and 3+ amorphous urates on urinalysis. Oliguric renal failure persisted despite aggressive hydration and diuretic use, requiring initiation of hemodialysis prior to chemotherapy. Antihyperuricemic therapy and hemodialysis were used to resolve hyperuricemia. However, due to multisystem organ dysfunction syndrome with extremely poor prognosis, the patient ultimately expired in the setting of a terminal ventilator wean. Although our patient did not meet current TLS criteria, she required hemodialysis due to uric acid nephropathy, a complication of TLS. This poses the clinical question of whether adequate diagnostic criteria exist for spontaneous TLS and if the lack of currently accepted guidelines has resulted in the underestimation of its incidence. Allopurinol and rasburicase are commonly used for prevention and treatment of TLS. Although both drugs decrease uric acid levels, allopurinol mechanistically prevents formation of the substrate rasburicase acts to solubilize. These drugs were administered together in our patient, although no established guidelines recommend combined use. This raises the clinical question of whether combined therapy is truly beneficial or, conversely, detrimental to patient outcomes.

  1. 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.

  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.

    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

  3. Generation and characterization of the human iPSC line PBMC1-iPS4F1 from adult peripheral blood mononuclear cells

    Directory of Open Access Journals (Sweden)

    Rosa Montes

    2015-11-01

    Full Text Available Here we describe the generation and characterization of the human induced pluripotent stem cell (iPSC line PBMC1-iPS4F1 from peripheral blood mononuclear cells from a healthy female with Spanish background. We used heat sensitive, non-integrative Sendai viruses containing the reprogramming factors Oct3/4, Sox2, Klf4 and c-Myc, whose expression was silenced in the established iPSC line. Characterization of the PBMC1-iPS4F1 cell line included analysis of typical pluripotency-associated factors at mRNA and protein level, alkaline phosphatase enzymatic activity, and in vivo and in vitro differentiation studies.

  4. 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....

  5. 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....

  6. DNA Damage and Oxidative Stress in Dyskeratosis Congenita: Analysis of Pathways and Therapeutic Stategies Using CPISPR and iPSC Model Systems

    Science.gov (United States)

    2017-06-01

    AWARD NUMBER: W81XWH-15-1-0099 TITLE: DNA Damage and Oxidative Stress in Dyskeratosis Congenita: Analysis of Pathways and Therapeutic...Oxidative Stress in Dyskeratosis Congenita: Analysis of Pathways and Therapeutic Stategies Using CPISPR and iPSC Model Systems 5c. PROGRAM ELEMENT...NUMBER 6. AUTHOR(S) Frederick Goldman, MD 5d. PROJECT NUMBER Erik Westin, PhD 5e. TASK NUMBER E-Mail: fgoldman@peds.uab.edu 5f. WORK UNIT NUMBER

  7. 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.

  8. 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.

  9. 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

    -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...

  10. iPhemap: an atlas of phenotype to genotype relationships of human iPSC models of neurological diseases.

    Science.gov (United States)

    Hollingsworth, Ethan W; Vaughn, Jacob E; Orack, Josh C; Skinner, Chelsea; Khouri, Jamil; Lizarraga, Sofia B; Hester, Mark E; Watanabe, Fumihiro; Kosik, Kenneth S; Imitola, Jaime

    2017-12-01

    Disease modeling with induced pluripotent stem cells (iPSCs) is creating an abundance of phenotypic information that has become difficult to follow and interpret. Here, we report a systematic analysis of research practices and reporting bias in neurological disease models from 93 published articles. We find heterogeneity in current research practices and a reporting bias toward certain diseases. Moreover, we identified 663 CNS cell-derived phenotypes from 243 patients and 214 controls, which varied by mutation type and developmental stage in vitro We clustered these phenotypes into a taxonomy and characterized these phenotype-genotype relationships to generate a phenogenetic map that revealed novel correlations among previously unrelated genes. We also find that alterations in patient-derived molecular profiles associated with cellular phenotypes, and dysregulated genes show predominant expression in brain regions with pathology. Last, we developed the iPS cell phenogenetic map project atlas (iPhemap), an open submission, online database to continually catalog disease phenotypes. Overall, our findings offer new insights into the phenogenetics of iPSC-derived models while our web tool provides a platform for researchers to query and deposit phenotypic information of neurological diseases. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  11. 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.

  12. 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.

  13. Evaluation of a miniature electromagnetic position tracker.

    Science.gov (United States)

    Hummel, Johann; Figl, Michael; Kollmann, Christian; Bergmann, Helmar; Birkfellner, Wolfgang

    2002-10-01

    The advent of miniaturized electromagnetic digitizers opens a variety of potential clinical applications for computer aided interventions using flexible instruments; endoscopes or catheters can easily be tracked within the body. With respect to the new applications, the systematic distortions induced by various materials such as closed metallic loops, wire guides, catheters, and ultrasound scan heads were systematically evaluated in this paper for a new commercial tracking system. We employed the electromagnetic tracking system Aurora (Mednetix/CH, NDI/Can); data were acquired using the serial port of a PC running SuSE Linux 7.1 (SuSE, Gmbh, Nürnberg). Objects introduced into the digitizer volume included wire loops of different diameters, wire guides, optical tracking tools, an ultrasonic (US) scan head, an endoscope with radial ultrasound scan head and various other objects used in operating rooms and interventional suites. Beyond this, we determined the influence of a C-arm fluoroscopy unit. To quantify the reliability of the system, the miniaturized sensor was mounted on a nonmetallic measurement rack while the transmitter was fixed at three different distances within the digitizer range. The tracker was shown to be more sensitive to distortions caused by materials close to the emitter (average distortion error 13.6 mm +/- 16.6 mm for wire loops positioned at a distance between 100 mm and 200 mm from the emitter). Distortions caused by materials near the sensor (distances smaller than 100 mm) are small (typical error 2.2 mm +/- 1.9 mm). The C-arm fluoroscopy unit caused considerable distortions and limits the reliability of the tracker (distortion error 18.6 mm +/- 24.9 mm). Distortions resulting from the US scan head are high at distances smaller than about 100 mm from the emitter. The distortions also increase when the scan head is positioned horizontally and close to the sensor (average error 4.1 mm +/- 1.5 mm when the scan head is positioned within a

  14. Miniaturized Airborne Imaging Central Server System

    Science.gov (United States)

    Sun, Xiuhong

    2011-01-01

    In recent years, some remote-sensing applications require advanced airborne multi-sensor systems to provide high performance reflective and emissive spectral imaging measurement rapidly over large areas. The key or unique problem of characteristics is associated with a black box back-end system that operates a suite of cutting-edge imaging sensors to collect simultaneously the high throughput reflective and emissive spectral imaging data with precision georeference. This back-end system needs to be portable, easy-to-use, and reliable with advanced onboard processing. The innovation of the black box backend is a miniaturized airborne imaging central server system (MAICSS). MAICSS integrates a complex embedded system of systems with dedicated power and signal electronic circuits inside to serve a suite of configurable cutting-edge electro- optical (EO), long-wave infrared (LWIR), and medium-wave infrared (MWIR) cameras, a hyperspectral imaging scanner, and a GPS and inertial measurement unit (IMU) for atmospheric and surface remote sensing. Its compatible sensor packages include NASA s 1,024 1,024 pixel LWIR quantum well infrared photodetector (QWIP) imager; a 60.5 megapixel BuckEye EO camera; and a fast (e.g. 200+ scanlines/s) and wide swath-width (e.g., 1,920+ pixels) CCD/InGaAs imager-based visible/near infrared reflectance (VNIR) and shortwave infrared (SWIR) imaging spectrometer. MAICSS records continuous precision georeferenced and time-tagged multisensor throughputs to mass storage devices at a high aggregate rate, typically 60 MB/s for its LWIR/EO payload. MAICSS is a complete stand-alone imaging server instrument with an easy-to-use software package for either autonomous data collection or interactive airborne operation. Advanced multisensor data acquisition and onboard processing software features have been implemented for MAICSS. With the onboard processing for real time image development, correction, histogram-equalization, compression, georeference, and

  15. Rhesus iPSC Safe Harbor Gene-Editing Platform for Stable Expression of Transgenes in Differentiated Cells of All Germ Layers.

    Science.gov (United States)

    Hong, So Gun; Yada, Ravi Chandra; Choi, Kyujoo; Carpentier, Arnaud; Liang, T Jake; Merling, Randall K; Sweeney, Colin L; Malech, Harry L; Jung, Moonjung; Corat, Marcus A F; AlJanahi, Aisha A; Lin, Yongshun; Liu, Huimin; Tunc, Ilker; Wang, Xujing; Palisoc, Maryknoll; Pittaluga, Stefania; Boehm, Manfred; Winkler, Thomas; Zou, Jizhong; Dunbar, Cynthia E

    2017-01-04

    Nonhuman primate (NHP) induced pluripotent stem cells (iPSCs) offer the opportunity to investigate the safety, feasibility, and efficacy of proposed iPSC-derived cellular delivery in clinically relevant in vivo models. However, there is need for stable, robust, and safe labeling methods for NHP iPSCs and their differentiated lineages to study survival, proliferation, tissue integration, and biodistribution following transplantation. Here we investigate the utility of the adeno-associated virus integration site 1 (AAVS1) as a safe harbor for the addition of transgenes in our rhesus macaque iPSC (RhiPSC) model. A clinically relevant marker gene, human truncated CD19 (hΔCD19), or GFP was inserted into the AAVS1 site in RhiPSCs using the CRISPR/Cas9 system. Genetically modified RhiPSCs maintained normal karyotype and pluripotency, and these clones were able to further differentiate into all three germ layers in vitro and in vivo. In contrast to transgene delivery using randomly integrating viral vectors, AAVS1 targeting allowed stable transgene expression following differentiation. Off-target mutations were observed in some edited clones, highlighting the importance of careful characterization of these cells prior to downstream applications. Genetically marked RhiPSCs will be useful to further advance clinically relevant models for iPSC-based cell therapies. Published by Elsevier Inc.

  16. 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.

  17. Infrared hyperspectral imaging miniaturized for UAV applications

    Science.gov (United States)

    Hinnrichs, Michele; Hinnrichs, Bradford; McCutchen, Earl

    2017-02-01

    Pacific Advanced Technology (PAT) has developed an infrared hyperspectral camera, both MWIR and LWIR, small enough to serve as a payload on a miniature unmanned aerial vehicles. The optical system has been integrated into the cold-shield of the sensor enabling the small size and weight of the sensor. This new and innovative approach to infrared hyperspectral imaging spectrometer uses micro-optics and will be explained in this paper. The micro-optics are made up of an area array of diffractive optical elements where each element is tuned to image a different spectral region on a common focal plane array. The lenslet array is embedded in the cold-shield of the sensor and actuated with a miniature piezo-electric motor. This approach enables rapid infrared spectral imaging with multiple spectral images collected and processed simultaneously each frame of the camera. This paper will present our optical mechanical design approach which results in an infrared hyper-spectral imaging system that is small enough for a payload on a mini-UAV or commercial quadcopter. Also, an example of how this technology can easily be used to quantify a hydrocarbon gas leak's volume and mass flowrates. The diffractive optical elements used in the lenslet array are blazed gratings where each lenslet is tuned for a different spectral bandpass. The lenslets are configured in an area array placed a few millimeters above the focal plane and embedded in the cold-shield to reduce the background signal normally associated with the optics. We have developed various systems using a different number of lenslets in the area array. Depending on the size of the focal plane and the diameter of the lenslet array will determine the spatial resolution. A 2 x 2 lenslet array will image four different spectral images of the scene each frame and when coupled with a 512 x 512 focal plane array will give spatial resolution of 256 x 256 pixel each spectral image. Another system that we developed uses a 4 x 4

  18. Miniaturized Interrogation System for Marsupial Rover Sensing Tether, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Luna proposes to continue development of its marsupial rover sensing tether (MaRS Tether) technology by miniaturizing the sensor's interrogation system. Luna is...

  19. Miniaturized fiber inline Fabry-Perot interferometer for chemical sensing.

    Science.gov (United States)

    2010-01-01

    This paper demonstrates the chemical sensing capability of a miniaturized fiber inline Fabry-Prot sensor fabricated by femtosecond : laser. Its accessible cavity enables the device to measure the refractive index within the cavity. The refractive i...

  20. 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...

  1. A Miniaturized and Robust FTS Sensor, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Vescent Photonics determined the feasibility of a miniaturized, robust, Fourier transform spectrometer (FTS) for either in-situ or remote chemical and spectral...

  2. A Miniaturized and Robust FTS Sensor, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Vescent Photonics details a miniaturized and robust Fourier transform spectrometer(FTS) for in-situ chemical and spectral analysis. Phase I research will focus on...

  3. Miniaturized Airborne Instrument for N2O, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Nitrous Oxide (N2O) is an important greenhouse gas, as well as a tracer for stratospheric air mass. We propose to design a miniaturized N2O detector based on direct...

  4. Miniature paint-spray gun for recessed areas

    Science.gov (United States)

    Vanasse, M. A.

    1968-01-01

    Miniature spray gun regulates paints and other liquids to spray at close range, facilitating spraying of remote or recessed areas. Individual valves for regulating air pressure and paint maximizes atomization for low pressure spraying.

  5. Miniature Space Dosimeter Based on Semiconductor Oxides Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Space Micro and Clemson University have teamed for a miniature, ultra low power, space radiation dosimeter. We project this unit, "MicroRad", to be 50X...

  6. 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...

  7. Miniature sonar for obstacle detection on samll AUV Maya

    Digital Repository Service at National Institute of Oceanography (India)

    Afzulpurkar, S.; Desa, E.; Navelkar, G.; Mascarenhas, A.A.M.Q.; Maurya, P.K.; Martins, H.; Madhan, R.; Prabhudesai, S.; Pinto, R.; Marchon, N.

    tasks. In this paper we describe the use of miniature two-dimensional scanning sonar, Micron, to generate obstacle information for Maya, the small AUV designed and built at National Institute of Oceanography, India. Micron is completely programmable...

  8. An Investigation Into the Performance of a Miniature Diesel Engine

    Science.gov (United States)

    Stevenson, P. W.

    1970-01-01

    Reports the procedures and results of a student investigation of the performance of a miniature diesel engine. The experiments include (1) torque measurement, (2) power measurement, and (3) variation of power output with applied load. Bibliography. (LC)

  9. 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...

  10. 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...

  11. 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....

  12. Miniature Nontoxic Nitrous Oxide-Propane (MINNOP) Propulsion Project

    Data.gov (United States)

    National Aeronautics and Space Administration — ORBITEC proposes to develop the Miniature Nontoxic Nitrous Oxide-Propane (MINNOP) propulsion system, a small bipropellant propulsion system which we offer as an...

  13. Simulation of translational piezoelectric microactuators with application in miniaturized robots

    Directory of Open Access Journals (Sweden)

    Marta Vílchez Monge

    2012-11-01

    Full Text Available In the design of miniaturized robots, different types of microelectromechanical actuators must be evaluated to determine the most appropriate one for each specific function as well as the best actuation effect for the size, force, supply voltage, energy, precision and degrees of freedom required.The piezoelectric effect is one of the most promising effects to incorporate microactuators in miniaturized robots. This paper presents a brief comparison on actuation methods for translational displacement and discusses its feasibility for application in miniaturized robots. The specific case of evaluation of a translational piezoelectric actuator using COMSOL Multiphysics is described, as well as an application example for a microgripper to be incorporated in a miniaturized robot for grasping submicrometric objects.

  14. Spontaneous Intracranial Hypotension

    International Nuclear Information System (INIS)

    Joash, Dr.

    2015-01-01

    Epidemiology is not only rare but an important cause of new daily persistent headaches among young & middle age individuals. The Etiology & Pathogenesis is generally caused by spinal CSF leak. Precise cause remains largely unknown, underlying structural weakness of spinal meninges is suspected. There are several MR Signs of Intracranial Hypotension that include:- diffuse pachymeningeal (dural) enhancement; bilateral subdural, effusion/hematomas; Downward displacement of brain; enlargement of pituitary gland; Engorgement of dural venous sinuses; prominence of spinal epidural venous plexus and Venous sinus thrombosis & isolated cortical vein thrombosis. The sum of volumes of intracranial blood, CSF & cerebral tissue must remain constant in an intact cranium. Treatment in Many cases can be resolved spontaneously or by use Conservative approach that include bed rest, oral hydration, caffeine intake and use of abdominal binder. Imaging Modalities for Detection of CSF leakage include CT myelography, Radioisotope cisternography, MR myelography, MR imaging and Intrathecal Gd-enhanced MR

  15. Spontaneous wave packet reduction

    International Nuclear Information System (INIS)

    Ghirardi, G.C.

    1994-06-01

    There are taken into account the main conceptual difficulties met by standard quantum mechanics in dealing with physical processes involving macroscopic system. It is stressed how J.A.Wheeler's remarks and lucid analysis have been relevant to pinpoint and to bring to its extreme consequences the puzzling aspects of quantum phenomena. It is shown how the recently proposed models of spontaneous dynamical reduction represent a consistent way to overcome the conceptual difficulties of the standard theory. Obviously, many nontrivial problems remain open, the first and more relevant one being that of generalizing the model theories considered to the relativistic case. This is the challenge of the dynamical reduction program. 43 refs, 2 figs

  16. The use of miniature implants as orthodontic anchorage in dogs

    OpenAIRE

    Toru, DEGUCHI; Ryuzo, KANOMI; Lawerence, GARETTO P.; Eugene, ROBERTS W.; Teruko, TAKANO; Department of Orthodontics, Okayama University Graduate School of Medicine and Dentistry; Kanomi Dental Clinic; Department of Oral Facial Development, Indiana University School of Dentistry; Department of Oral Facial Development, Indiana University School of Dentistry; Department of Orthodontics, Okayama University Graduate School of Medicine and Dentistry

    2002-01-01

    In the past decade, there have been many attempts to use implants as anchorage devices. Unfortunately, previous reports limit the use of these implants for anchorage because of their large size. Clinically, in cases such as intrusion of molars are necessary, small implants placed between the roots of teeth would be a great benefit for the orthodontist. The objective of this study was to histomorphometrically (static) analyze the use of miniature implants. A total of 20 miniature implants (1.0...

  17. Evaluation of BJTs as Closing Switch of Miniaturized Marx Generator

    OpenAIRE

    Yamada, Chiemi; Ueno, Takahisa; Namihira, Takao; Sakugawa, Takashi; Katsuki, Sunao; Akiyama, Hidenori; ヤマダ, チエミ; ウエノ, タカヒサ; ナミヒラ, タカオ; サクガワ, タカシ; カツキ, スナオ; アキヤマ, ヒデノリ; 山田, 千恵美; 上野, 崇寿; 浪平, 隆男

    2007-01-01

    The micro plasma technology is used in various fieldssuch as processing or chemical analysis of minutematerial, short-wavelength light source, and plasmafunction device. The plasmas can be generated by anelectric discharge. The miniaturized generator was used toproduce these plasmas in the micro-scale area. For suchbackground, the miniaturized Marx generator which hasBipolar Junction Transistors (BJTs) as closing switcheswas developed to generate micro plasmas. In theminiaturized Marx generat...

  18. Reestablishment of radiographic kidney size in Miniature Schnauzer dogs

    OpenAIRE

    SOHN, Jungmin; YUN, Sookyung; LEE, Jeosoon; CHANG, Dongwoo; CHOI, Mincheol; YOON, Junghee

    2016-01-01

    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 ...

  19. 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

  20. A photodiode based miniature sun sensor

    International Nuclear Information System (INIS)

    Lü, Xiaozhou; Tao, Yebo; Xie, Kai; Wang, Songlin; Li, Xiaoping; Bao, Weimin; Chen, Renjie

    2017-01-01

    The solar vector is one of the most important parameters for attitude control of nanosatellites. This attitude control must be achieved without the sensors adding significantly to its size or mass. This paper presents a photodiode-based miniature sun sensor, which consists of two triangular pyramidal sensor unit structures, with each unit comprising three micro-silicon photodiodes. The two sensor units are installed on the diagonal of the nanosatellite to form a complete sun sensor capable of achieving a full-field range of solar vector measurements. In this paper, the mathematical model of the short-circuit currents of the silicon photodiodes as a function of the solar vector coordinates is deduced. A sensor sample was built and installed on a nanosatellite model, and the temperature compensation coefficient of the silicon photodiodes was obtained experimentally. The dynamic characteristic, linearity, hysteresis and repeatability of the component were measured. The sun sensor introduced in this paper can be placed on any satellite platform to allow a full range solar vector measurement, and this would result in an increase of only 1.86 g and 0.9 cm 3 of the satellite’s mass and volume, respectively. (paper)

  1. Computational investigation of miniature trailing edge effectors

    Science.gov (United States)

    Lee, Hak-Tae

    Miniature trailing edge effectors (MiTEs) are small flaps (typically 1% to 5% chord) actuated with deflection angles of up to 90 degrees. The small size, combined with little required power and good control authority, enables the device to be used for high bandwidth control as well as conventional attitude control. However, some of the aerodynamic characteristics of these devices are complex and poorly understood. This research investigated the aerodynamics of MiTEs using incompressible Navier-Stokes flow solvers, INS2D and INS3D. To understand the flow structure and establish a parametric database, two dimensional steady-state computations were performed for MiTEs with various geometries and flow conditions. Time accurate computations were used to resolve the unsteady characteristics including transient response and vortex shedding phenomena. The frequency response was studied to fully identify the dynamics of MiTEs. Three dimensional computations show the change in control effectiveness with respect to the spanwise length of MiTEs as well as the spanwise lift distribution induced by these devices. Based on the CFD results, an approximate vortex panel model was developed for design purposes that reproduces the key characteristics of MiTEs. Two application areas for MiTEs were explored. Flutter suppression was demonstrated by combining a finite element structural model with the vortex panel model. The application of MiTEs to augment maximum lift and improve the post stall behavior of an airfoil was also investigated.

  2. Recent Advances in Miniaturized Optical Gyroscopes

    Science.gov (United States)

    Dell'Olio, F.; Tatoli, T.; Ciminelli, C.; Armenise, M. N.

    2014-03-01

    Low-cost chip-scale optoelectronic gyroscopes having a resolution ≤ 10 °/h and a good reliability also in harsh environments could have a strong impact on the medium/high performance gyro market, which is currently dominated by well-established bulk optical angular velocity sensors. The R&D activity aiming at the demonstration of those miniaturized sensors is crucial for aerospace/defense industry, and thus it is attracting an increasing research effort and notably funds. In this paper the recent technological advances on the compact optoelectronic gyroscopes with low weight and high energy saving are reviewed. Attention is paid to both the so-called gyroscope-on-a-chip, which is a novel sensor, at the infantile stage, whose optical components are monolithically integrated on a single indium phosphide chip, and to a new ultra-high Q ring resonator for gyro applications with a configuration including a 1D photonic crystal in the resonant path. The emerging field of the gyros based on passive ring cavities, which have already shown performance comparable with that of optical fiber gyros, is also discussed.

  3. Miniaturization and globalization of clinical laboratory activities.

    Science.gov (United States)

    Melo, Murilo R; Clark, Samantha; Barrio, Daniel

    2011-04-01

    Clinical laboratories provide an invaluable service to millions of people around the world in the form of quality diagnostic care. Within the clinical laboratory industry the impetus for change has come from technological development (miniaturization, nanotechnology, and their collective effect on point-of-care testing; POCT) and the increasingly global nature of laboratory services. Potential technological gains in POCT include: the development of bio-sensors, microarrays, genetics and proteomics testing, and enhanced web connectivity. In globalization, prospective opportunities lie in: medical tourism, the migration of healthcare workers, cross-border delivery of testing, and the establishment of accredited laboratories in previously unexplored markets. Accompanying these impressive opportunities are equally imposing challenges. Difficulty transitioning from research to clinical use, poor infrastructure in developing countries, cultural differences and national barriers to global trade are only a few examples. Dealing with the issues presented by globalization and the impact of developing technology on POCT, and on the clinical laboratory services industry in general, will be a daunting task. Despite such concerns, with appropriate countermeasures it will be possible to address the challenges posed. Future laboratory success will be largely dependent on one's ability to adapt in this perpetually shifting landscape.

  4. A locust-inspired miniature jumping robot.

    Science.gov (United States)

    Zaitsev, Valentin; Gvirsman, Omer; Ben Hanan, Uri; Weiss, Avi; Ayali, Amir; Kosa, Gabor

    2015-11-25

    Unmanned ground vehicles are mostly wheeled, tracked, or legged. These locomotion mechanisms have a limited ability to traverse rough terrain and obstacles that are higher than the robot's center of mass. In order to improve the mobility of small robots it is necessary to expand the variety of their motion gaits. Jumping is one of nature's solutions to the challenge of mobility in difficult terrain. The desert locust is the model for the presented bio-inspired design of a jumping mechanism for a small mobile robot. The basic mechanism is similar to that of the semilunar process in the hind legs of the locust, and is based on the cocking of a torsional spring by wrapping a tendon-like wire around the shaft of a miniature motor. In this study we present the jumping mechanism design, and the manufacturing and performance analysis of two demonstrator prototypes. The most advanced jumping robot demonstrator is power autonomous, weighs 23 gr, and is capable of jumping to a height of 3.35 m, covering a distance of 1.37 m.

  5. 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

  6. 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

  7. Spontaneous Pneumomediastinum: Hamman Syndrome

    Directory of Open Access Journals (Sweden)

    Tushank Chadha, BS

    2018-04-01

    significant fat stranding. The image also showed an intraluminal stent traversing the gastric antrum and gastric pylorus with no indication of obstruction. Circumferential mural thickening of the gastric antrum and body were consistent with the patient’s history of gastric adenocarcinoma. The shotty perigastric lymph nodes with associated fat stranding, along the greater curvature of the distal gastric body suggested local regional nodal metastases and possible peritoneal carcinomatosis. The thoracic CT scans showed extensive pneumomediastinum that tracked into the soft tissues of the neck, which given the history of vomiting also raised concern for esophageal perforation. There was still no evidence of mediastinal abscess or fat stranding. Additionally, a left subclavian vein port catheter, which terminates with tip at the cavoatrial junction of the superior vena cava can also be seen on the image. Discussion: Spontaneous Pneumomediastinum, also known as Hamman syndrome, is defined by the uncommon incidence of free air in the mediastinum due to the bursting of alveoli, as a result of extended spells of shouting, coughing, or vomiting.1,2 The condition is diagnosed when a clear cause (aerodigestive rupture, barotrauma, infection secondary to gas-forming organisms3 for pneumomediastinum cannot be clearly identified on diagnostic studies. Macklin and Macklin were the first to note the pathogenesis of the syndrome and explained that the common denominator to spontaneous pneumomediastinum was that increased alveolar pressure leads to alveolar rupture.3 Common clinical findings for spontaneous pneumomediastinum include: chest pain, dyspnea, cough, and emesis.4 The condition is not always readily recognized on initial presentation in part for its rare incidence, estimated to be approximately 1 in every 44,500 ED patients3and also because of the non-specific presenting symptoms. For this patient, there was no clear singular cause, and therefore she received care for spontaneous

  8. A miniature magnetic waveguide for cold atoms

    International Nuclear Information System (INIS)

    Key, M.G.

    2000-09-01

    This thesis presents the first demonstration of a guide for cold atoms based on a miniature structure of four current-carrying wires. The four wires are embedded within a hollow silica fibre. Atoms are guided along the centre of a fifth hole on the axis of the fibre by the Stern-Gerlach force. A vapour cell Magneto Optical Trap (MOT), formed 1 cm above the mouth of the waveguide is the source of cold 85 Rb atoms. After cooling the atoms to 25 μK in optical molasses they fall under the influence of gravity through a magnetic funnel into the waveguide. After propagating for 2 cm, the atoms are reflected by the field of a small pinch coil wound around the base of the guide. The atoms then travel back up the fibre and out into the funnel, where they can be imaged either in fluorescence or by recapturing in the MOT. A video sequence of atoms falling into the guide and re-emerging after reflection from the pinch coil graphically illustrates the operation of the guide. The coupling efficiency and transverse temperature of the atoms is measured experimentally and in a Monte-Carlo simulation. We find an optimum coupling efficiency of 12% and we measure the spatial extent of the cloud within the fibre to be of order 100 μm. We find good agreement between experimental data and results from the numerical simulation. We have also been able to observe different thresholds for the reflection of different positive m F levels. In another experiment we are able to trap the atoms in an elongated Ioffe trap for up to two seconds, increasing the distance over which the atoms are guided. We are able to guide the atoms over distances of 40 cm with a loss rate indistinguishable from the free space loss rate. (author)

  9. Spontaneous breaking of supersymmetry

    Energy Technology Data Exchange (ETDEWEB)

    Zumino, B.

    1981-12-01

    There has been recently a revival of interest in supersymmetric gauge theories, stimulated by the hope that supersymmetry might help in clarifying some of the questions which remain unanswered in the so called Grand Unified Theories and in particular the gauge hierarchy problem. In a Grand Unified Theory one has two widely different mass scales: the unification mass M approx. = 10/sup 15/GeV at which the unification group (e.g. SU(5)) breaks down to SU(3) x SU(2) x U(1) and the mass ..mu.. approx. = 100 GeV at which SU(2) x U(1) is broken down to the U(1) of electromagnetism. There is at present no theoretical understanding of the extreme smallness of the ratio ..mu../M of these two numbers. This is the gauge hierarchy problem. This lecture attempts to review the various mechanisms for spontaneous supersymmetry breaking in gauge theories. Most of the discussions are concerned with the tree approximation, but what is presently known about radiative correction is also reviewed.

  10. Spontaneous intracranial hypotension

    International Nuclear Information System (INIS)

    Haritanti, A.; Karacostas, D.; Drevelengas, A.; Kanellopoulos, V.; Paraskevopoulou, E.; Lefkopoulos, A.; Economou, I.; Dimitriadis, A.S.

    2009-01-01

    Spontaneous intracranial hypotension (SIH) is an uncommon but increasingly recognized syndrome. Orthostatic headache with typical findings on magnetic resonance imaging (MRI) are the key to diagnosis. Delayed diagnosis of this condition may subject patients to unnecessary procedures and prolong morbidity. We describe six patients with SIH and outline the important clinical and neuroimaging findings. They were all relatively young, 20-54 years old, with clearly orthostatic headache, minimal neurological signs (only abducent nerve paresis in two) and diffuse pachymeningeal gadolinium enhancement on brain MRI, while two of them presented subdural hygromas. Spinal MRI was helpful in detecting a cervical cerebrospinal fluid leak in three patients and dilatation of the vertebral venous plexus with extradural fluid collection in another. Conservative management resulted in rapid resolution of symptoms in five patients (10 days-3 weeks) and in one who developed cerebral venous sinus thrombosis, the condition resolved in 2 months. However, this rapid clinical improvement was not accompanied by an analogous regression of the brain MR findings that persisted on a longer follow-up. Along with recent literature data, our patients further point out that SIH, to be correctly diagnosed, necessitates increased alertness by the attending physician, in the evaluation of headaches

  11. Spontaneous lateral temporal encephalocele.

    Science.gov (United States)

    Tuncbilek, Gokhan; Calis, Mert; Akalan, Nejat

    2013-01-01

    A spontaneous encephalocele is one that develops either because of embryological maldevelopment or from a poorly understood postnatal process that permits brain herniation to occur. We here report a rare case of lateral temporal encephalocele extending to the infratemporal fossa under the zygomatic arch. At birth, the infant was noted to have a large cystic mass in the right side of the face. After being operated on initially in another center in the newborn period, the patient was referred to our clinic with a diagnosis of temporal encephalocele. He was 6 months old at the time of admission. Computerized tomography scan and magnetic resonance imaging studies revealed a 8 × 9 cm fluid-filled, multiloculated cystic mass at the right infratemporal fossa. No intracranial pathology or connection is seen. The patient was operated on to reduce the distortion effect of the growing mass. The histopathological examination of the sac revealed well-differentiated mature glial tissue stained with glial fibrillary acid protein. This rare clinical presentation of encephaloceles should be taken into consideration during the evaluation of the lateral facial masses in the infancy period, and possible intracranial connection should be ruled out before surgery to avoid complications.

  12. Bilateral spontaneous carotid artery dissection.

    Science.gov (United States)

    Townend, Bradley Scott; Traves, Laura; Crimmins, Denis

    2005-06-01

    Bilateral internal carotid artery dissections have been reported, but spontaneous bilateral dissections are rare. Internal carotid artery dissection can present with a spectrum of symptoms ranging from headache to completed stroke. Two cases of spontaneous bilateral carotid artery dissection are presented, one with headache and minimal symptoms and the other with a stroke syndrome. No cause could be found in either case, making the dissections completely spontaneous. Bilateral internal carotid artery dissection (ICAD) should be considered in young patients with unexplained head and neck pain with or without focal neurological symptoms and signs. The increasing availability of imaging would sustain the higher index of suspicion.

  13. Mini Mass Spectrometer Integrated with a Miniature Ion Funnel.

    Science.gov (United States)

    Zhai, Yanbing; Zhang, Xiaohua; Xu, Hualei; Zheng, Yongchang; Yuan, Tao; Xu, Wei

    2017-04-04

    Previously, a continuous atmospheric pressure interfaced miniature mass spectrometer was developed in our lab. The continuous atmospheric pressure interface improves system robustness, stability, and scan speed, but it also results in limited ion transfer efficiency and reduced mass resolution. To solve these problems, a miniature ion funnel was designed and integrated into the miniature mass spectrometer for the first time. Besides ion transfer efficiency, dimension and power consumption of the ion funnel also need to be considered throughout the design process. After a systematic optimization, the designed miniature ion funnel could increase ion transfer efficiency by more than 10 times, while lowering the background pressure of ion trap by ∼2 times. As a result, sensitivity and mass resolution of the second generation miniature mass spectrometer were improved by 20 times and ∼2 times, respectively, while maintaining its high scan speed and stability. A sensitive and robust mini-MS, capable of coupling with ambient ionization sources would meet the needs of many on-site chemical analysis applications, such as in food, drug, and agricultural administrations, forensic science, homeland security, and etc.

  14. 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.

  15. Effect of temperature on a miniaturized microbial fuel cell (MFC)

    Science.gov (United States)

    Ren, Hao; Jiang, Chenming; Chae, Junseok

    2017-12-01

    A microbial fuel cell (MFC) is a bioinspired energy converter which directly converts biomass into electricity through the catalytic activity of a specific species of bacteria. The effect of temperature on a miniaturized microbial fuel cell with Geobacter sulfurreducens dominated mixed inoculum is investigated in this paper for the first time. The miniaturized MFC warrants investigation due to its small thermal mass, and a customized setup is built for the temperature effect characterization. The experiment demonstrates that the optimal temperature for the miniaturized MFC is 322-326 K (49-53 °C). When the temperature is increased from 294 to 322 K, a remarkable current density improvement of 282% is observed, from 2.2 to 6.2 Am-2. Furthermore, we perform in depth analysis on the effect of temperature on the miniaturized MFC, and found that the activation energy for the current limiting mechanism of the MFC is approximately between 0.132 and 0.146 eV, and the result suggest that the electron transfer between cytochrome c is the limiting process for the miniaturized MFC.

  16. A miniature forward-imaging optical coherence tomography (OCT) probe

    Science.gov (United States)

    Joos, Karen M.; Shen, Jin-Hui

    2012-03-01

    Optical coherence tomography (OCT) has had a tremendous global health impact upon the current ability to diagnose, treat, and monitor multiple eye diseases. We propose that a miniature forward-imaging OCT probe can be developed for real-time ocular imaging. A miniature 25-gauge forward-imaging probe was designed and developed to use with an 850 nm spectral-domain optical coherence tomography (SDOCT) system (Bioptigen, Inc. Durham, NC). Imaging parameters were determined. Ocular tissues were examined with the miniature OCT probe. A miniature SDOCT probe was developed with the scanning driver within the hand piece. The SDOCT fiber-scanning probe maximally transmitted power of 800 μW. The scanning range was 3 mm when the probe tip was held 3 to 5 mm from the tissue surface. The axial resolution was 6 μm and the lateral resolution was 30-35 μm. The 25-gauge forward-imaging probe was used to image cellophane tape, eyelid skin, cornea, conjunctiva, sclera, iris, anterior lens, anterior chamber angle, retina, retinal tear, retinal detachment, optic nerve head, and optic nerve sheath. Images obtained from the miniature probe appeared similar to images from a 3 mm scanning range of a commercial large handheld OCT probe (Bioptigen, Inc. Durham, NC).

  17. 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.

  18. 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

  19. Spontaneous ischaemic stroke in dogs

    DEFF Research Database (Denmark)

    Gredal, Hanne Birgit; Skerritt, G. C.; Gideon, P.

    2013-01-01

    Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms.......Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms....

  20. Spontaneity and international marketing performance

    OpenAIRE

    Souchon, Anne L.; Hughes, Paul; Farrell, Andrew M.; Nemkova, Ekaterina; Oliveira, Joao S.

    2016-01-01

    The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Purpose – The purpose of this paper is to ascertain how today’s international marketers can perform better on the global scene by harnessing spontaneity. Design/methodology/approach – The authors draw on contingency theory to develop a model of the spontaneity – international marketing performance relationship, and identify three potential m...

  1. Differential calcium dependence in basal and forskolin-potentiated spontaneous transmitter release in basolateral amygdala neurons.

    Science.gov (United States)

    Miura, Yuki; Naka, Masamitsu; Matsuki, Norio; Nomura, Hiroshi

    2012-10-31

    Action potential-independent transmitter release, or spontaneous release, is postulated to produce multiple postsynaptic effects (e.g., maintenance of dendritic spines and suppression of local dendritic protein synthesis). Potentiation of spontaneous release may contribute to the precise modulation of synaptic function. However, the expression mechanism underlying potentiated spontaneous release remains unclear. In this study, we investigated the involvement of extracellular and intracellular calcium in basal and potentiated spontaneous release. Miniature excitatory postsynaptic currents (mEPSCs) of the basolateral amygdala neurons in acute brain slices were recorded. Forskolin, an adenylate cyclase activator, increased mEPSC frequency, and the increase lasted at least 25 min after washout. Removal of the extracellular calcium decreased mEPSC frequency in both naïve and forskolin-treated slices. On the other hand, chelation of intracellular calcium by BAPTA-AM decreased mEPSC frequency in naïve, but not in forskolin-treated slices. A blockade of the calcium-sensing receptor (CaSR) resulted in an increase in mEPSC frequency in forskolin-treated, but not in naïve slices. These findings indicate that forskolin-induced potentiation is accompanied by changes in the mechanisms underlying Ca(2+)-dependent spontaneous release. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. 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.

  3. 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

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Petr Dymáček

    2018-01-01

    Full Text Available 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.

  6. 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

  7. 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)

  8. 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.

  9. Miniaturization of Multiple-Layer Folded Patch Antennas

    DEFF Research Database (Denmark)

    Zhang, Jiaying; Breinbjerg, Olav

    2009-01-01

    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......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...

  10. 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.

  11. Miniaturized Air-to-Refrigerant Heat Exchangers

    Energy Technology Data Exchange (ETDEWEB)

    Radermacher, Reinhard [Univ. of Maryland, College Park, MD (United States); Bacellar, Daniel [Univ. of Maryland, College Park, MD (United States); Aute, Vikrant [Univ. of Maryland, College Park, MD (United States); Huang, Zhiwei [Univ. of Maryland, College Park, MD (United States); Hwang, Yunho [Univ. of Maryland, College Park, MD (United States); Ling, Jiazhen [Univ. of Maryland, College Park, MD (United States); Muehlbauer, Jan [Univ. of Maryland, College Park, MD (United States); Tancabel, James [Univ. of Maryland, College Park, MD (United States); Abdelaziz, Omar [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Zhang, Mingkan [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-05-23

    Air-to-refrigerant Heat eXchangers (HX) are an essential component of Heating, Ventilation, Air-Conditioning, and Refrigeration (HVAC&R) systems, serving as the main heat transfer component. The major limiting factor to HX performance is the large airside thermal resistance. Recent literature aims at improving heat transfer performance by utilizing enhancement methods such as fins and small tube diameters; this has lead to almost exhaustive research on the microchannel HX (MCHX). The objective of this project is to develop a miniaturized air-to-refrigerant HX with at least 20% reduction in volume, material volume, and approach temperature compared to current state-of-the-art multiport flat tube designs and also be capable of production within five years. Moreover, the proposed HX’s are expected to have good water drainage and should succeed in both evaporator and condenser applications. The project leveraged Parallel-Parametrized Computational Fluid Dynamics (PPCFD) and Approximation-Assisted Optimization (AAO) techniques to perform multi-scale analysis and shape optimization with the intent of developing novel HX designs whose thermal-hydraulic performance exceeds that of state-of-the-art MCHX. Nine heat exchanger geometries were initially chosen for detailed analysis, selected from 35+ geometries which were identified in previous work at the University of Maryland, College Park. The newly developed optimization framework was exercised for three design optimization problems: (DP I) 1.0kW radiator, (DP II) 10kW radiator and (DP III) 10kW two-phase HX. DP I consisted of the design and optimization of 1.0kW air-to-water HX’s which exceeded the project requirements of 20% volume/material reduction and 20% better performance. Two prototypes for the 1.0kW HX were prototyped, tested and validated using newly-designed airside and refrigerant side test facilities. DP II, a scaled version DP I for 10kW air-to-water HX applications, also yielded optimized HX designs

  12. 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

  13. 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.)

  14. Optical antenna enhanced spontaneous emission.

    Science.gov (United States)

    Eggleston, Michael S; Messer, Kevin; Zhang, Liming; Yablonovitch, Eli; Wu, Ming C

    2015-02-10

    Atoms and molecules are too small to act as efficient antennas for their own emission wavelengths. By providing an external optical antenna, the balance can be shifted; spontaneous emission could become faster than stimulated emission, which is handicapped by practically achievable pump intensities. In our experiments, InGaAsP nanorods emitting at ∼ 200 THz optical frequency show a spontaneous emission intensity enhancement of 35 × corresponding to a spontaneous emission rate speedup ∼ 115 ×, for antenna gap spacing, d = 40 nm. Classical antenna theory predicts ∼ 2,500 × spontaneous emission speedup at d ∼ 10 nm, proportional to 1/d(2). Unfortunately, at d antenna efficiency drops below 50%, owing to optical spreading resistance, exacerbated by the anomalous skin effect (electron surface collisions). Quantum dipole oscillations in the emitter excited state produce an optical ac equivalent circuit current, I(o) = qω|x(o)|/d, feeding the antenna-enhanced spontaneous emission, where q|x(o)| is the dipole matrix element. Despite the quantum-mechanical origin of the drive current, antenna theory makes no reference to the Purcell effect nor to local density of states models. Moreover, plasmonic effects are minor at 200 THz, producing only a small shift of antenna resonance frequency.

  15. Functional Restoration of gp91phox-Oxidase Activity by BAC Transgenesis and Gene Targeting in X-linked Chronic Granulomatous Disease iPSCs.

    Science.gov (United States)

    Laugsch, Magdalena; Rostovskaya, Maria; Velychko, Sergiy; Richter, Cornelia; Zimmer, Ariane; Klink, Barbara; Schröck, Evelin; Haase, Michael; Neumann, Katrin; Thieme, Sebastian; Roesler, Joachim; Brenner, Sebastian; Anastassiadis, Konstantinos

    2016-04-01

    Chronic granulomatous disease (CGD) is an inherited immunodeficiency, caused by the inability of neutrophils to produce functional NADPH oxidase required for fighting microbial infections. The X-linked form of CGD (X-CGD), which is due to mutations in the CYBB (gp91phox) gene, a component of NADPH oxidase, accounts for about two-thirds of CGD cases. We derived induced pluripotent stem cells (iPSCs) from X-CGD patient keratinocytes using a Flp recombinase excisable lentiviral reprogramming vector. For restoring gp91phox function, we applied two strategies: transposon-mediated bacterial artificial chromosome (BAC) transgenesis and gene targeting using vectors with a fixed 5' homology arm (HA) of 8 kb and 3'HA varying in size from 30 to 80 kb. High efficiency of homologous recombination (up to 22%) was observed with increased size of the 3'HA. Both, BAC transgenesis and gene targeting resulted in functional restoration of the gp91phox measured by an oxidase activity assay in X-CGD iPSCs differentiated into the myeloid lineage. In conclusion, we delivered an important milestone towards the use of genetically corrected autologous cells for the treatment of X-CGD and monogenic diseases in general.

  16. 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...

  17. 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

  18. modified edge fed sierpinski carpet miniaturized microstrip patch ...

    African Journals Online (AJOL)

    user

    2016-07-03

    Jul 3, 2016 ... Simulation results showed that the proposed antenna achieved 46.5% size reduction when compared with the main patch antenna without affecting the resonant frequency and radiation patterns. Keywords: Microstrip patch antenna, fractal antenna, Miniaturization, Sierpinski Carpet. 1. INTRODUCTION.

  19. Reducing Unsteady Loads on a Piggyback Miniature Submarine

    Science.gov (United States)

    Lin, John

    2009-01-01

    A small, simple fixture has been found to be highly effective in reducing destructive unsteady hydrodynamic loads on a miniature submarine that is attached in piggyback fashion to the top of a larger, nuclear-powered, host submarine. The fixture, denoted compact ramp, can be installed with minimal structural modification, and the use of it does not entail any change in submarine operations.

  20. 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.

  1. 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).

  2. 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

  3. A miniaturized silicon based device for nucleic acids electrochemical detection

    Directory of Open Access Journals (Sweden)

    Salvatore Petralia

    2015-12-01

    The system and the method here reported offer better advantages in term of analytical performances compared to the standard commercial optical-based real-time PCR systems, with the additional incomes of being potentially cheaper and easier to integrate in a miniaturized device.

  4. Adventitious shoot regeneration from leaf explants of miniature ...

    African Journals Online (AJOL)

    Seeds of miniature paprika (Capsicum annuum) 'Hivita Red' and 'Hivita Yellow' were decontaminated and placed in a petri dish containing a half-strength MS medium and then were incubated in the dark for 7 10 ... Morphology and fruit shape of regenerated plants were normal and plants set seeds as the same as to the ...

  5. 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.

  6. 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...

  7. Pyometra and complete vaginal adhesion in a miniature horse

    OpenAIRE

    Cozens, Elizabeth R.W.

    2009-01-01

    A 4-year-old miniature horse experienced intermittent episodes of pyrexia, lethargy, and purulent vaginal discharge following dsytocia. Vaginal endoscopy and transrectal ultrasonography revealed a blind-ending vaginal cavity and distended uterus. Surgical treatment was declined and the mare was euthanized. Post-mortem examination confirmed the diagnosis of pyometra and vaginal adhesions.

  8. 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.

  9. 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 ...

  10. 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

  11. 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.

  12. Spontaneous subcapsular and perirrenal hemorrhage

    International Nuclear Information System (INIS)

    Fuster, M.J.; Saez, J.; Perez-Paya, F.J.; Fernandez, F.

    1997-01-01

    To assess the role of CT in the etiologic diagnosis of spontaneous subcapsular and perirrenal hemorrhage. The CT findings are described in 13 patients presenting subcapsular and perirrenal hemorrhage. Those patients in whom the bleeding was not spontaneous were excluded. Surgical confirmation was obtained in nine cases. In 11 of the 13 cases (84.6%), involving five adenocarcinomas, five angiomyolipoma, two complicated cysts and one case of panarterities nodosa, CT disclosed the underlying pathology. In two cases (15.4%), it only revealed the extension of the hematoma, but gave no clue to its origin. CT is the technique of choice when spontaneous subcapsular and perirrenal hemorrhage is suspected since, in most cases, it reveals the underlying pathology. (Author)

  13. Spontaneous isolated celiac artery dissection

    Directory of Open Access Journals (Sweden)

    Tuba Cimilli Ozturk

    2011-01-01

    Full Text Available Dyspepsia with mild, stabbing epigastric discomfort without history of trauma is a very common symptom that emergency physicians see in their daily practice. Vascular emergencies, mostly the aortic dissection and aneurysm, are always described in the differential diagnosis with persistent symptoms. Isolated celiac artery dissection occurring spontaneously is a very rare diagnosis. The involvement of branch vessels is generally observed and patients show various clinical signs and symptoms according to the involved branch vessel. Here we are presenting a case with spontaneous isolated celiac artery dissection, without any branch vessel involvement or visceral damage, detected by computed tomography scans taken on admission.

  14. Spontaneous waves in muscle fibres

    Energy Technology Data Exchange (ETDEWEB)

    Guenther, Stefan; Kruse, Karsten [Department of Theoretical Physics, Saarland University, 66041 Saarbruecken (Germany); Max Planck Institute for the Physics of Complex Systems, Noethnitzer Street 38, 01187 Dresden (Germany)

    2007-11-15

    Mechanical oscillations are important for many cellular processes, e.g. the beating of cilia and flagella or the sensation of sound by hair cells. These dynamic states originate from spontaneous oscillations of molecular motors. A particularly clear example of such oscillations has been observed in muscle fibers under non-physiological conditions. In that case, motor oscillations lead to contraction waves along the fiber. By a macroscopic analysis of muscle fiber dynamics we find that the spontaneous waves involve non-hydrodynamic modes. A simple microscopic model of sarcomere dynamics highlights mechanical aspects of the motor dynamics and fits with the experimental observations.

  15. Human Papillomavirus Infection as a Possible Cause of Spontaneous Abortion and Spontaneous Preterm Delivery

    DEFF Research Database (Denmark)

    Ambühl, Lea Maria Margareta; Baandrup, Ulrik; Dybkær, Karen

    2016-01-01

    , and 10.9% (95% CI; 10.1–11.7) for umbilical cord blood. Summary estimates for HPV prevalence of spontaneous abortions and spontaneous preterm deliveries, in cervix (spontaneous abortions: 24.5%, and pretermdeliveries: 47%, resp.) and placenta (spontaneous abortions: 24.9%, and preterm deliveries: 50......%, resp.), were identified to be higher compared to normal full-term pregnancies (푃 spontaneous abortion, spontaneous preterm...

  16. 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

  17. Spontaneous Development of Moral Concepts

    Science.gov (United States)

    Siegal, M.

    1975-01-01

    Moral competence is more difficult to attain than scientific competence. Since language comprehension plays a central role in conceptual development, and moral language is difficult to learn, there is a common deficiency in moral conceptual development. This suggests a theory of non-spontaneous solutions to moral problems. (Author/MS)

  18. Shell theorem for spontaneous emission

    DEFF Research Database (Denmark)

    Kristensen, Philip Trøst; Mortensen, Jakob Egeberg; Lodahl, Peter

    2013-01-01

    and therefore is given exactly by the dipole approximation theory. This surprising result is a spontaneous emission counterpart to the shell theorems of classical mechanics and electrostatics and provides insights into the physics of mesoscopic emitters as well as great simplifications in practical calculations....

  19. Prediction of Spontaneous Preterm Birth

    NARCIS (Netherlands)

    Dijkstra, Karolien

    2002-01-01

    Preterm birth is a leading cause of neonatal morbidity and mortality. It is a major goal in obstetrics to lower the incidence of spontaneous preterm birth (SPB) and related neonatal morbidity and mortality. One of the principal objectives is to discover early markers that would allow us to identify

  20. EAMJ Dec. Spontaneous.indd

    African Journals Online (AJOL)

    2008-12-12

    Dec 12, 2008 ... surgical abortion at one month gestation without any complication. The second pregnancy which was a year prior resulted in a spontaneous miscarriage at two months followed by evacuation of retained products of conception with no post abortion complications. Antibiotics were taken following both.

  1. Spontaneous fission of superheavy nuclei

    Indian Academy of Sciences (India)

    the Yukawa-plus-exponential potential. The microscopic shell and pairing corrections are obtained using the Strutinsky and BCS approaches and the cranking formulae yield the inertia tensor. Finally, the WKB method is used to calculate penetrabilities and spontaneous fission half-lives. Calculations are performed for the ...

  2. 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.

  3. Spontaneous Retropharyngeal Emphysema: A Case Report | Chi ...

    African Journals Online (AJOL)

    ... is a rare clinical condition in pediatric otolaryngology. The predominant symptoms are sore throat, odynophagia, dysphagia, and neck pain. Here, we report a case of spontaneous retropharyngeal emphysema. Keywords: Iatrogenic injury, retropharyngeal emphysema, spontaneous retropharyngeal emphysem, trauma ...

  4. La maladie de Grisel : Spontaneous atlantoaxial subluxation

    NARCIS (Netherlands)

    Meek, MF; Robinson, PH; Hermens, RAEC

    Objective: "La maladie de Grisel" (Grisel's syndrome) is a spontaneously occurring atlantoaxial subluxation with torticollis. We present a case of atlantoaxial subluxation occurring in a 20-year period of pharyngoplasty surgery. The occurrence of a "spontaneous" atlantoaxial subluxation after oral

  5. 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...

  6. Uterine lesions in 32 female miniature pet pigs.

    Science.gov (United States)

    Ilha, M R S; Newman, S J; van Amstel, S; Fecteau, K A; Rohrbach, B W

    2010-11-01

    Thirty-two 4-month-old to 19-year-old female miniature pet pigs were spayed. Uterine lesions were present in all except 8 pigs. The 24 remaining pigs had diffuse cystic endometrial hyperplasia, of which 14 had smooth muscle tumors, including leiomyomas and leiomyosarcomas, in the uterus or broad ligament. Nodular endometrial lesions-including adenocarcinomas, adenomas, and/or adenomyosis-were present in 10 pigs, 3 of which had concurrent smooth muscle tumors. Pyometra was present in 3 pigs. In uterine sections with cystic endometrial hyperplasia, adenomyosis, or adenomas, approximately 70% of epithelial nuclei expressed estrogen receptor and progesterone receptor immunohistochemically; in adenocarcinomas, expression was 20%. Regardless of malignancy, more than 50% of nuclei in smooth muscle tumors expressed estrogen receptor and progesterone receptor. Aging was associated with the development of uterine lesions in miniature pet pigs.

  7. 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.

  8. Miniaturized electronic system for the Planetary Integrated Camera-Spectrometer

    Science.gov (United States)

    Soll, Stanley L.; Graham, Richard; Ramirez, Luis J.

    1994-09-01

    This paper discusses the design, and implementation of a miniaturized electronic system for the Planetary Integrated Camera Spectrometer (PICS). The PICS electronics demonstrate the application of Field Programmable Gate Arrays (FPGAs) and of analog hybrid technology to space flight multi-spectral systems. A discussion of the electronic system design illustrates how signals from a multi-sensor instrument containing an UV CCD, two visible CCDs, and a near-IR focal plane assembly can be processed through a common set of electronics. Following the system design discussion, the actual electronic design will be presented. Each miniaturized module will be discussed as to functionality and performance. The test setup for bench checkout of a cooled CCD and an IR FPA, including results with breadboard electronics and with the hybrids are also described.

  9. 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

  10. 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.

  11. 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

  12. Determining mechanical behavior of solid materials using miniature specimens

    Science.gov (United States)

    Manahan, M.P.; Argon, A.S.; Harling, O.K.

    1986-02-04

    A Miniaturized Bend Test (MBT) capable of extracting and determining mechanical behavior information from specimens only so large as to have at least a volume or smallest dimension sufficient to satisfy continuum behavior in all directions is disclosed. The mechanical behavior of the material is determined from the measurements taken during the bending of the specimen and is processed according to the principles of linear or nonlinear material mechanics or both. In a preferred embodiment the determination is carried out by a code which is constructed according to the finite element method, and the specimen used for the determinations is a miniature disk simply supported for central loading at the axis on the center of the disk. 51 figs.

  13. 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

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

    Directory of Open Access Journals (Sweden)

    Cristina Mora

    2017-10-01

    Full Text Available Atrial fibrillation (AF is the most common sustained arrhythmia associated with several cardiac risk factors, but increasing evidences indicated a genetic component. Indeed, genetic variations of the specific PITX2 gene have been identified in patients with early-onset AF. To investigate 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.

  15. Generation and characterization of a human iPSC cell line expressing inducible Cas9 in the “safe harbor” AAVS1 locus

    Directory of Open Access Journals (Sweden)

    Julio Castaño

    2017-05-01

    Full Text Available We report the generation-characterization of a fetal liver (FL B-cell progenitor (BCP-derived human induced pluripotent stem cell (hiPSC line CRISPR/Cas9-edited to carry/express a single copy of doxycycline-inducible Cas9 gene in the “safe locus” AAVS1 (iCas9-FL-BCP-hiPSC. Gene-edited iPSCs remained pluripotent after CRISPR/Cas9 genome-edition. Correct genomic integration of a unique copy of Cas9 was confirmed by PCR and Southern blot. Cas9 was robustly and specifically expressed on doxycycline exposure. T7-endonuclease assay demonstrated that iCas9 induces robust gene-edition when gRNAs against hematopoietic transcription factors were tested. This iCas9-FL-BCP-hiPSC will facilitate gene-editing approaches for studies on developmental biology, drug screening and disease modeling.

  16. Establishment of human iPSC line NCCSi003-A from CD34+cells of peripheral blood collected during apheresis of healthy donor from Indian ethnicity.

    Science.gov (United States)

    Fernandes, Sophia; Tembe, Shruti; Shinde, Prajakta; Melinkeri, Sameer; Kale, Vaijayanti; Limaye, Lalita

    2018-03-01

    We present generation of iPSCs from CD34 + cells isolated from peripheral blood, collected during apheresis of a healthy female individual. We nucleofected the CD34 + cells by episomal vectors containing Oct4, Sox2, L-Myc, Lin28, Klf4 and p53DD (dominant negative mutation in p53). The resultant colonies showed cobble-stone appearance and stained positive for alkaline phosphatase. The colonies demonstrated presence of pluripotency markers by immunofluorescence, flow-cytometry and PCR. The plasmids were lost from cells subsequently during passages as assessed by PCR. Karyotype analysis demonstrated a stable genome. The cells had capability to differentiate to cells from all three-germ lineages in vitro. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Establishment of human iPSC line NCCSi003-A from CD34+cells of peripheral blood collected during apheresis of healthy donor from Indian ethnicity

    Directory of Open Access Journals (Sweden)

    Sophia Fernandes

    2018-03-01

    Full Text Available We present generation of iPSCs from CD34+ cells isolated from peripheral blood, collected during apheresis of a healthy female individual. We nucleofected the CD34+cells by episomal vectors containing Oct4, Sox2, L-Myc, Lin28, Klf4 and p53DD (dominant negative mutation in p53. The resultant colonies showed cobble-stone appearance and stained positive for alkaline phosphatase. The colonies demonstrated presence of pluripotency markers by immunofluorescence, flow-cytometry and PCR. The plasmids were lost from cells subsequently during passages as assessed by PCR. Karyotype analysis demonstrated a stable genome. The cells had capability to differentiate to cells from all three-germ lineages in vitro.

  18. Generation of induced pluripotent stem cells (iPSCs from a Bernard–Soulier syndrome patient carrying a W71R mutation in the GPIX gene

    Directory of Open Access Journals (Sweden)

    Lourdes Lopez-Onieva

    2016-05-01

    Full Text Available We generated an induced pluripotent stem cell (iPSC line from a Bernard–Soulier Syndrome (BSS patient carrying the mutation p.Trp71Arg in the GPIX locus (BSS1-PBMC-iPS4F4. Peripheral blood mononuclear cells (PBMCs were reprogrammed using heat sensitive non-integrative Sendai viruses containing the reprogramming factors Oct3/4, SOX2, KLF4 and c-MYC. Successful silencing of the exogenous reprogramming factors was checked by RT-PCR. Characterization of BSS1-PBMC-iPS4F4 included mutation analysis of GPIX locus, Short Tandem Repeats (STR profiling, alkaline phosphatase enzymatic activity, analysis of conventional pluripotency-associated factors at mRNA and protein level and in vivo differentiation studies. BSS1-PBMC-iPS4F4 will provide a powerful tool to study BSS.

  19. 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.

  20. 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.

  1. Size Matters: Problems and Advantages Associated with Highly Miniaturized Sensors

    OpenAIRE

    Dahlin, Andreas B.

    2012-01-01

    There is no doubt that the recent advances in nanotechnology have made it possible to realize a great variety of new sensors with signal transduction mechanisms utilizing physical phenomena at the nanoscale. Some examples are conductivity measurements in nanowires, deflection of cantilevers and spectroscopy of plasmonic nanoparticles. The fact that these techniques are based on the special properties of nanostructural entities provides for extreme sensor miniaturization since a single structu...

  2. 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

  3. Cooling SABER with a miniature pulse tube refrigerator

    Science.gov (United States)

    Jensen, Scott M.; Batty, J. Clair; Roettker, William A.; Felt, Matthew J.

    1998-09-01

    Utah State University/Space Dynamics Laboratory, teaming with NASA Langley Research Center, is currently building the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument. Stringent mass and power constraints, together with a greater than two year mission life, led to the selection of a TRW miniature pulse tube refrigerator to cool SABER's infrared detectors to the required temperature of 75 K. This paper provides an overview of the SABER thermal management plan and the challenges encountered in matching the refrigerator characteristics with instrument performance requirements under the broadly variant space environments expected for this mission. Innovative technologies were developed to keep heat loads within the limited cooling capacity of the miniature refrigerator, as well as mechanically isolating but thermally connecting the refrigerator cold block to the focal plane assembly (FPA). A passive radiator will maintain the SABER telescope at an average temperature of 230 K while a separate radiator will reject heat from the refrigerator and electronics at approximately 260 K. Significant breadboard tests of various components of the SABER instrument have taken place and the details of one of these will be discussed. The test included attaching a miniature mechanical refrigerator, borrowed from the Air Force, to the SABER FPA. This opportunity gave the SABER team a significant head start in learning about integrating and testing issues related with the TRW miniature pulse tube refrigerator. SABER is scheduled to be launched in January 2000 as the primary instrument of NASA's TIMED (Thermosphere-Ionosphere-Mesosphere Energetics and Dynamics) spacecraft. The TIMED program is being managed by the Applied Physics Laboratory at Johns Hopkins University.

  4. 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.

  5. 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

  6. Characterization of the hydrodynamics in a miniaturized dissolution apparatus

    DEFF Research Database (Denmark)

    Johansson, Kristoffer E; Plum, Jakob; Mosleh, Majid

    2018-01-01

    The hydrodynamics of a miniaturized dissolution apparatus was characterized using computational fluid dynamics (CFD) simulations and analyzed in relation to the biorelevance and robustness of measurements of drug dissolution and precipitation kinetics from supersaturated drug solutions. The effect...... geometry influences the hydrodynamics of the system and indicates that an off-center probe position may result in more robust measurements. Furthermore, the study shows that the agitator geometry has a significant effect on supersaturation studies due to differences in the hydrodynamic shear produced...

  7. 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.

  8. Fabrication of Miniature Thermoelectric Generators Using Bulk Materials

    Science.gov (United States)

    Joo, Sung-Jae; Ryu, Byungki; Min, Bok-Ki; Lee, Ji-Eun; Kim, Bong-Seo; Park, Su-Dong; Lee, Hee-Woong

    2016-07-01

    Miniature thermoelectric modules (TEMs) are required for micro power generation as well as local cooling, and they should have small size and high performance. However, conventional bulk TEMs generally have in-plane dimensions of a few centimeters, and empty space between the legs for electrical isolation makes efficient miniaturization difficult. In this study, a miniature TEM with footprint of about 0.35 cm2 and leg height of 0.97 mm was fabricated by reducing the dimensions of the legs and attaching them together to form a closely packed assembly, without using microelectromechanical processes. First, Bi0.4Sb1.6Te3 (BST) and Bi2Te2.7Se0.3 (BTS) ingots were made by ball milling and spark plasma sintering, and the ingots were cut into thin plates. These BST and BTS plates were then attached alternately using polyimide tapes, and the attached plates were sliced vertically to produce thin sheets. This process was repeated once again to make chessboard-like assemblies having 20 p- n pairs in an area of 0.35 cm2, and electrical contacts were formed by Ni sputtering and Ag paste coating. Finally, thermally conductive silicone pads (~500 μm) were attached on both sides of the assembly using electrically insulating interface thermal tapes (˜180 μm). The maximum output power ( P max) from the miniature module was about 28 μW and 2.0 mW for temperature difference (Δ T) of 5.6°C and 50.5°C, respectively. Reducing the contact resistance was considered to be the key to increase the output power.

  9. Conceptual Design and Simulation of a Miniature Plasma Focus

    International Nuclear Information System (INIS)

    Jafari, H.; Habibi, M.; Amrollahi, R.

    2012-01-01

    Design and construction of a miniature plasma focus device with 3.6 J of energy bank is reported. In design the device, some of very important parameters of designing such as plasma energy density and derive parameter was used. Regarding to the electrical and geometrical parameters of the device, a simulation is carried out by MATLAB software. Simulation results showed that the formation of the pinch have occurred at the moment of the peak discharge current.

  10. Miniature osmotic actuators for controlled maxillofacial distraction osteogenesis

    Science.gov (United States)

    Li, Yu-Hsien; Su, Yu-Chuan

    2010-06-01

    We have successfully demonstrated miniature actuators that are capable of converting chemical potential directly into steady mechanical movements for maxillofacial distraction osteogenesis. Pistons and diaphragms powered by osmosis are employed to provide the desired linear and volumetric displacements for bone distraction and potentially the release of bone morphogenetic proteins, respectively. The cylindrical-shaped miniature actuators are composed of polymeric materials and fabricated by molding and assembly processes. In the prototype demonstration, vapor-permeable thermoplastic polyurethane was employed as the semi-permeable material. 3 cm long actuators with piston and diaphragm radii of 1 mm and 500 µm, respectively, were fabricated and characterized. The maximum distraction force from the piston-type actuator is found to be 6 N while the piston travels at a constant velocity of 32 µm h-1 (or 0.77 mm/day) for about 1 week. Meanwhile, the release rate from the diaphragm-type actuator is measured to be constant, 0.15 µl h-1 (or 3.6 µl/day), throughout the experiment. Moreover, the sizes and output characteristics of the self-regulating actuators could readily be tailored to realize optimal distraction rate, rhythm and osteogenic activity. As such, the demonstrated miniature osmotic actuators could potentially serve as versatile apparatuses for maxillofacial distraction osteogenesis and fulfill the needs of a variety of implantable and biomedical applications.

  11. Adaptive measurement method for miniature spectrometers used in cold environments.

    Science.gov (United States)

    Wang, Hangzhou; Nan, Liwen; Huang, Hui; Yang, Ping; Song, Hong; Han, Jiwan; Wu, Yuanqian; Yan, Tingting; Yuan, Zhuoli; Chen, Ying

    2017-10-01

    Adaptive measurement is a major concern when using miniature spectrometers in extreme environments, especially when the ambient temperatures and incident light intensities vary greatly. In this study, parameters, including the signal output and the relevant noise and signal-to-noise ratio (SNR) of a fiber optic spectrometry system composed of a photodiode array miniature spectrometer and external driver electronics were examined at multiple integration times from -50°C to 30°C, well below the specified operating temperature of this spectrometer. The relationships between those parameters and incident light level were also examined, at a single temperature of 0°C. Based on these examinations, temperature-induced biases in the linear operating range of the spectrometer were identified. Signal output and the relevant noise and SNR in response to different integration times, temperatures, and incident light levels were assessed separately. These assessments were then used to develop an adaptive measurement method for estimating the incident light level and setting up an optimal integration time for this spectrometer, while autonomously adapting the variation in the ambient temperature and incident light level simultaneously. This approach provides a general framework for developing an adaptive measurement algorithm for miniature spectrometers, which face tremendous variations in ambient temperature and incident light level.

  12. 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.

  13. 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.

  14. 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.

  15. An open source, wireless capable miniature microscope system

    Science.gov (United States)

    Liberti, William A., III; Perkins, L. Nathan; Leman, Daniel P.; Gardner, Timothy J.

    2017-08-01

    Objective. Fluorescence imaging through head-mounted microscopes in freely behaving animals is becoming a standard method to study neural circuit function. Flexible, open-source designs are needed to spur evolution of the method. Approach. We describe a miniature microscope for single-photon fluorescence imaging in freely behaving animals. The device is made from 3D printed parts and off-the-shelf components. These microscopes weigh less than 1.8 g, can be configured to image a variety of fluorophores, and can be used wirelessly or in conjunction with active commutators. Microscope control software, based in Swift for macOS, provides low-latency image processing capabilities for closed-loop, or BMI, experiments. Main results. Miniature microscopes were deployed in the songbird premotor region HVC (used as a proper name), in singing zebra finches. Individual neurons yield temporally precise patterns of calcium activity that are consistent over repeated renditions of song. Several cells were tracked over timescales of weeks and months, providing an opportunity to study learning related changes in HVC. Significance. 3D printed miniature microscopes, composed completely of consumer grade components, are a cost-effective, modular option for head-mounting imaging. These easily constructed and customizable tools provide access to cell-type specific neural ensembles over timescales of weeks.

  16. 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.

  17. Systematics of spontaneous positron lines

    International Nuclear Information System (INIS)

    Mueller, U.; Reus, T. de; Reinhardt, J.; Mueller, B.; Greiner, W.

    1985-08-01

    Dynamical and spontaneous positron emission are investigated for heavy-ion collisions with long time delay using a semiclassical description. Numerical results and analytical expressions for the characteristic quantities of the resulting spontaneous positron line, i.e., its position, width, and cross section, are compared. The expected behaviour of the line position and cross section and its visibility against the spectrum of dynamically created positrons is discussed in dependence of the united charge Zsub(u) of projectile and target nucleus in a range of systems from Zsub(u)=180 up to Zsub(u)=188. The results are confronted with presently available experimental data, and possible implications on further experiments are worked out. (orig.)

  18. Spontaneous Rotational Inversion in Phycomyces

    KAUST Repository

    Goriely, Alain

    2011-03-01

    The filamentary fungus Phycomyces blakesleeanus undergoes a series of remarkable transitions during aerial growth. During what is known as the stagea IV growth phase, the fungus extends while rotating in a counterclockwise manner when viewed from above (stagea IVa) and then, while continuing to grow, spontaneously reverses to a clockwise rotation (stagea IVb). This phase lasts for 24-48Ah and is sometimes followed by yet another reversal (stageAIVc) before the overall growth ends. Here, we propose a continuum mechanical model of this entire process using nonlinear, anisotropic, elasticity and show how helical anisotropy associated with the cell wall structure can induce spontaneous rotation and, under appropriate circumstances, the observed reversal of rotational handedness. © 2011 American Physical Society.

  19. Spontaneous regression of colon cancer.

    Science.gov (United States)

    Kihara, Kyoichi; Fujita, Shin; Ohshiro, Taihei; Yamamoto, Seiichiro; Sekine, Shigeki

    2015-01-01

    A case of spontaneous regression of transverse colon cancer is reported. A 64-year-old man was diagnosed as having cancer of the transverse colon at a local hospital. Initial and second colonoscopy examinations revealed a typical cancer of the transverse colon, which was diagnosed as moderately differentiated adenocarcinoma. The patient underwent right hemicolectomy 6 weeks after the initial colonoscopy. The resected specimen showed only a scar at the tumor site, and no cancerous tissue was proven histologically. The patient is alive with no evidence of recurrence 1 year after surgery. Although an antitumor immune response is the most likely explanation, the exact nature of the phenomenon was unclear. We describe this rare case and review the literature pertaining to spontaneous regression of colorectal cancer. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Management of intractable spontaneous epistaxis

    Science.gov (United States)

    Rudmik, Luke

    2012-01-01

    Background: Epistaxis is a common otolaryngology emergency and is often controlled with first-line interventions such as cautery, hemostatic agents, or anterior nasal packing. A subset of patients will continue to bleed and require more aggressive therapy. Methods: Intractable spontaneous epistaxis was traditionally managed with posterior nasal packing and prolonged hospital admission. In an effort to reduce patient morbidity and shorten hospital stay, surgical and endovascular techniques have gained popularity. A literature review was conducted. Results: Transnasal endoscopic sphenopalatine artery ligation and arterial embolization provide excellent control rates but the decision to choose one over the other can be challenging. The role of transnasal endoscopic anterior ethmoid artery ligation is unclear but may be considered in certain cases when bleeding localizes to the ethmoid region. Conclusion: This article will focus on the management of intractable spontaneous epistaxis and discuss the role of endoscopic arterial ligation and embolization as it pertains to this challenging clinical scenario. PMID:22391084

  1. Spontaneous baryogenesis in warm inflation

    OpenAIRE

    Brandenberger, Robert H.; Yamaguchi, Masahide

    2003-01-01

    We discuss spontaneous baryogenesis in the warm inflation scenario. In contrast with standard inflation models, radiation always exists in the warm inflation scenario, and the inflaton must be directly coupled to it. Also, the transition to the post-inflationary radiation dominated phase is smooth and the entropy is not significantly increased at the end of the period of inflation. In addition, after the period of warm inflation ends, the inflaton does not oscillate coherently but slowly roll...

  2. Spontaneous Splenic Rupture in Melanoma

    Directory of Open Access Journals (Sweden)

    Hadi Mirfazaelian

    2014-01-01

    Full Text Available Spontaneous rupture of spleen due to malignant melanoma is a rare situation, with only a few case reports in the literature. This study reports a previously healthy, 30-year-old man who came with chief complaint of acute abdominal pain to emergency room. On physical examination, abdominal tenderness and guarding were detected to be coincident with hypotension. Ultrasonography revealed mild splenomegaly with moderate free fluid in abdominopelvic cavity. Considering acute abdominal pain and hemodynamic instability, he underwent splenectomy with splenic rupture as the source of bleeding. Histologic examination showed diffuse infiltration by tumor. Immunohistochemical study (positive for S100, HMB45, and vimentin and negative for CK, CD10, CK20, CK7, CD30, LCA, EMA, and chromogranin confirmed metastatic malignant melanoma. On further questioning, there was a past history of a nasal dark skin lesion which was removed two years ago with no pathologic examination. Spontaneous (nontraumatic rupture of spleen is an uncommon situation and it happens very rarely due to neoplastic metastasis. Metastasis of malignant melanoma is one of the rare causes of the spontaneous rupture of spleen.

  3. 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

  4. Transcriptional landscape of a RETC634Y-mutated iPSC and its CRISPR-corrected isogenic control reveals the putative role of EGR1 transcriptional program in the development of multiple endocrine neoplasia type 2A-associated cancers

    Directory of Open Access Journals (Sweden)

    Julien Hadoux

    2018-01-01

    Full Text Available MEN2A is a hereditary cancer-predisposing syndrome that affects patients with germline RET mutations. The effects of this oncogenic tyrosine kinase in the context of primitive stem cells are not known. In order to study these events, we generated a MEN2A induced Pluripotent Stem Cell (iPSC line from a patient with RET mutation and an isogenic counterpart by CRISPR-Cas9 correction of the mutation. Whole exome sequencing of iPSC before and after CRISPR-Cas9 genome edition revealed no major exonic off target effect of the CRISPR correction. However, an integrative differential gene expression analysis of iPSC with oncogenic RETC634Y and its gene-corrected iPSC with RETY634C as well as RETwt iPSCs revealed activation of the Early Growth Response 1 (EGR1 transcriptional program in RET-mutated iPSC, a pathway shown to be involved in RET-induced oncogenesis. These data constitute the first proof of concept of the feasibility of the use of an iPSC and its genome-corrected counterpart to unravel the molecular mechanisms underlying the development of the hereditary MEN2A cancer predisposing syndrome.

  5. The design and characterisation of miniature bioreactors for microbial fermentation process development.

    OpenAIRE

    Betts, J. I.

    2006-01-01

    This thesis focuses on the design and characterisation of miniature bioreactors and evaluates their potential as a scale-down device for microbial cultivation processes. Miniature bioreactors, such as the one detailed in this work, have been developed by many research groups and companies, and seek to increase throughput at the early stages of bioprocess development. Power input was measured in two prototype stirred-tank miniature bioreactors (10 ml and 25 ml) as a function of impeller speed ...

  6. Identification of variants of the SPINK1 gene and their association with pancreatitis in Miniature Schnauzers.

    Science.gov (United States)

    Bishop, Micah A; Xenoulis, Panagiotis G; Levinski, Melinda D; Suchodolski, Jan S; Steiner, Jörg M

    2010-05-01

    To evaluate the serine protease inhibitor, Kazal type 1 (SPINK1) gene for variants and to determine their possible association with pancreatitis in Miniature Schnauzers. 39 Miniature Schnauzers with pancreatitis, 25 healthy Miniature Schnauzers, and 23 healthy dogs of other breeds. The entire canine SPINK1 gene with its intron-exon boundaries was initially sequenced in 22 Miniature Schnauzers. Then, 2 regions of the gene were sequenced in 65 additional canine DNA samples at the locations of variants identified in the initial sequencing of the entire SPINK1 gene. Analysis of the SPINK1 gene in Miniature Schnauzers revealed 3 closely associated variants in healthy Miniature Schnauzers and Miniature Schnauzers with pancreatitis. These variants consisted of 2 missense mutations in the second exon (N20K and N25T) and a poly T insertion in the third intron that was near the boundary of exon 3 (IVS3+26-27ins(T)33-39,15_61dup11). Pancreatitis was significantly associated with homozygous alleles for these 3 variants in Miniature Schnauzers. In healthy dogs of other breeds, only the 2 exon variants were identified. Variants of the SPINK1 gene may be associated with the development of pancreatitis in Miniature Schnauzers.

  7. MER2 MARS MINIATURE THERMAL EMISSION SPECTROMETER BTR V1.0

    Data.gov (United States)

    National Aeronautics and Space Administration — This archive contains Mars Exploration Rover Miniature Thermal Emission Spectrometer (Mini-TES) Brightness Temperature Reduced Data Record (BTR) products and...

  8. 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...

  9. MER2 MARS MINIATURE THERMAL EMISSION SPECTROMETER EMR V1.0

    Data.gov (United States)

    National Aeronautics and Space Administration — This archive contains Mars Exploration Rover Miniature Thermal Emission Spectrometer (Mini-TES) Emissivity Reduced Data Record (EMR) products and ancillary files....

  10. MER2 MARS MINIATURE THERMAL EMISSION SPECTROMETER EDR V1.0

    Data.gov (United States)

    National Aeronautics and Space Administration — This archive contains Mars Exploration Rover Miniature Thermal Emission Spectrometer (Mini-TES) Experiment Data Record (EDR) products and ancillary files. The...

  11. MER1 MARS MINIATURE THERMAL EMISSION SPECTROMETER BTR V1.0

    Data.gov (United States)

    National Aeronautics and Space Administration — This archive contains Mars Exploration Rover Miniature Thermal Emission Spectrometer (Mini-TES) Brightness Temperature Reduced Data Record (BTR) products and...

  12. MER1 MARS MINIATURE THERMAL EMISSION SPECTROMETER EMR V1.0

    Data.gov (United States)

    National Aeronautics and Space Administration — This archive contains Mars Exploration Rover Miniature Thermal Emission Spectrometer (Mini-TES) Emissivity Reduced Data Record (EMR) products and ancillary files....

  13. 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...

  14. Spontaneous oscillations in microfluidic networks

    Science.gov (United States)

    Case, Daniel; Angilella, Jean-Regis; Motter, Adilson

    2017-11-01

    Precisely controlling flows within microfluidic systems is often difficult which typically results in systems being heavily reliant on numerous external pumps and computers. Here, I present a simple microfluidic network that exhibits flow rate switching, bistablity, and spontaneous oscillations controlled by a single pressure. That is, by solely changing the driving pressure, it is possible to switch between an oscillating and steady flow state. Such functionality does not rely on external hardware and may even serve as an on-chip memory or timing mechanism. I use an analytic model and rigorous fluid dynamics simulations to show these results.

  15. General features of spontaneous baryogenesis

    Science.gov (United States)

    Arbuzova, Elena

    2017-04-01

    The classical version of spontaneous baryogenesis is studied in details. It is shown that the relation between the time derivative of the (pseudo)goldstone field and the baryonic chemical potential essentially depends upon the representation chosen for the fermionic fields with non-zero baryonic number (quarks). The kinetic equation, used for the calculations of the cosmological baryon asymmetry, is generalized to the case of non-stationary background. The effects of the finite interval of the integration over time are also included into consideration.

  16. Spontaneous osteonecrosis of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Kattapuram, Taj M. [Department of Radiology, Massachusetts General Hospital (United States); Kattapuram, Susan V. [Department of Radiology, Massachusetts General Hospital (United States)], E-mail: skattapuram@partners.org

    2008-07-15

    Spontaneous osteonecrosis of the knee presents with acute onset of severe, pain in elderly patients, usually female and usually without a history of trauma. Originally described as idiopathic osteonecrosis, the exact etiology is still debated. Evidence suggests that an acute fracture occurs as a result of chronic stress or minor trauma to a weakened subchondral bone plate. The imaging characteristics on MR reflect the age of the lesion and the symptoms. More appropriate terminology may be ' subchondral insufficiency fracture of the knee' or 'focal subchondral osteonecrosis'.

  17. 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.

  18. Generation of an inbred miniature pig model of retinitis pigmentosa.

    Science.gov (United States)

    Ross, Jason W; Fernandez de Castro, Juan P; Zhao, Jianguo; Samuel, Melissa; Walters, Eric; Rios, Cecilia; Bray-Ward, Patricia; Jones, Bryan W; Marc, Robert E; Wang, Wei; Zhou, Liang; Noel, Jennifer M; McCall, Maureen A; DeMarco, Paul J; Prather, Randall S; Kaplan, Henry J

    2012-01-31

    The Pro23His (P23H) rhodopsin (RHO) mutation underlies the most common form of human autosomal dominant retinitis pigmentosa (adRP). The objective of this investigation was to establish a transgenic miniature swine model of RP using the human P23H RHO gene. Somatic cell nuclear transfer (SCNT) was used to create transgenic miniature pigs that expressed the human P23H RHO mutation. From these experiments, six transgenic founders were identified whose retinal function was studied with full-field electroretinography (ffERG) from 3 months through 2 years. Progeny from one founder were generated and genotyped to determine transgene inheritance pattern. Retinal mRNA was isolated, and the ratio of P23H to wild-type pig RHO was measured. A single transgene integration site was observed for five of the six founders. All founders had abnormal scotopic and photopic ffERGs after 3 months. The severity of the ffERG phenotype was grouped into moderately and severely affected groups. Offspring of one founder inherited the transgene as an autosomal dominant mutation. mRNA analyses demonstrated that approximately 80% of total RHO was mutant P23H. Expression of the human RHO P23H transgene in the retina creates a miniature swine model with an inheritance pattern and retinal function that mimics adRP. This large-animal model can serve as a novel tool for the study of the pathogenesis and therapeutic intervention in the most common form of adRP.

  19. 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.

  20. Design Feasibility Study for a Demultiplexer Miniaturized for Microtomographic Imaging

    Science.gov (United States)

    Lang, Udo; Trtik, Pavel; Notter, Manuela; Hovind, Jan; Lehmann, Eberhard H.

    In this paper a design feasibility study of a miniaturized demultiplexer that allows for simultaneous tomographic imaging on three independent rotational axes. While the general concept has been proven on a larger scale for three centimeter sized samples, the downscaling of this concept is presented herein. The main requirements are firstly, positioning of the samples parallel to the detector screen for stable imaging and secondly, the use of backlash free gears to avoid any angular play. Based on these requirements a concept is shown that consists of three precisely positioned anti-backlash axes within a housing with a spacing of 3.5 mm.

  1. 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

  2. Controlling the Plasma Flow in the Miniaturized Cylindrical Hall Thruster

    International Nuclear Information System (INIS)

    Smirnov, A.; Raitses, Y.; Fisch, N.J.

    2008-01-01

    A substantial narrowing of the plume of the cylindrical Hall thruster (CHT) was observed upon the enhancement of the electron emission from the hollow cathode discharge, which implies the possibility for the thruster efficiency increase due to the ion beam focusing. It is demonstrated that the miniaturized CHT can be operated in the non-self-sustained regime, with the discharge current limited by the cathode electron emission. The thruster operation in this mode greatly expands the range of the plasma and discharge parameters normally accessible for the CHT.

  3. Miniaturized Wide-Range Field-Emission Vacuum Gauge

    OpenAIRE

    Avdić, Amra; Lausch, Anna Maria; Bertagnolli, Emmerich; Lugstein, Alois

    2014-01-01

    Miniaturized vacuum gauges (MVGs) for the measurement range 5.7x10-7 to 1.1x10-2 mbar were fabricated in a self-aligned approach using focused ion beam (FIB) nanomachining and reactive ion etching (RIE). The MVG consists of two properly insulated electrodes integrated on top of an atomic force microscopy (AFM) tip, forming a coaxial embodiment. The special design enables us to vary the cathode-anode separation and the turn-on voltage changes accordingly. The experiments show that the MVGs ope...

  4. Performance test of miniature heat exchangers with microchannels

    International Nuclear Information System (INIS)

    Hong, Yong Ju; Koh, Deuk Yong

    2005-01-01

    Etched microchannel heat exchanger, a subfield within MEMS, has high heat flux capability. This capability makes microchannels well-suited for a wide variety of application of cooling and chemical reaction. In this study, counter flow type miniature heat exchangers, which have flat metal plates with chemically etched microchannels, were manufactured by brazing method. Four type of the heat exchangers, which have straight microchannels, wavy shape microchannels, pin-fin channels and serpentine shape microchannels, were investigated to compare their thermal and hydraulic performance. Gas to gas heat exchange experiments were performed to measure the pressure drop and effectiveness of the heat exchangers at given gas flow rates and temperature difference

  5. Miniaturized fatigue crack growth specimen technology and results

    International Nuclear Information System (INIS)

    Puigh, R.J.; Bauer, R.E.; Ermi, A.M.; Chin, B.A.

    1981-01-01

    The miniature fatigue crack propagation technology has been extended to in-cell fabrication of irradiated specimens. Baseline testing of selected titanium alloys has been performed at 25 0 C in air. At relatively small values for the stress intensity factor, ΔK, the crack growth rates for all titanium alloys investigated are within a factor of three. The crack growth rates for these titanium alloys are a factor of three greater than the crack growth rates of either 316SS (20% CW) or HT-9. Each of the titanium alloys has observable crack propagation for stress intensity factors as small as 4.2 MPa√m

  6. A miniature fuel reformer system for portable power sources

    Science.gov (United States)

    Dolanc, Gregor; Belavič, Darko; Hrovat, Marko; Hočevar, Stanko; Pohar, Andrej; Petrovčič, Janko; Musizza, Bojan

    2014-12-01

    A miniature methanol reformer system has been designed and built to technology readiness level exceeding a laboratory prototype. It is intended to feed fuel cells with electric power up to 100 W and contains a complete setup of the technological elements: catalytic reforming and PROX reactors, a combustor, evaporators, actuation and sensing elements, and a control unit. The system is engineered not only for performance and quality of the reformate, but also for its lightweight and compact design, seamless integration of elements, low internal electric consumption, and safety. In the paper, the design of the system is presented by focussing on its miniaturisation, integration, and process control.

  7. Data Collection using Miniature Aerial Vehicles in Wireless Sensor Networks

    DEFF Research Database (Denmark)

    Mathur, Prateek; Nielsen, Rasmus Hjorth; Prasad, Neeli R.

    2016-01-01

    Energy constraints of sensor nodes in wireless sensor networks (WSNs) is a major challenge and minimising the overall data transmitted across a network using data aggregation, distributed source coding, and compressive sensing have been proposed as mechanisms for energy saving. Similarly, use...... of mobile nodes capable of relocating within the network has been widely explored for energy saving. In this paper, we propose a novel method for using miniature aerial vehicles (MAVs) for data collection instead of actively sensing from a deployed network. The proposed mechanism is referred as Data...

  8. Optimization of electrostatically actuated miniature compressors for electronics cooling

    Energy Technology Data Exchange (ETDEWEB)

    Sathe, Abhijit A.; Groll, Eckhard A.; Garimella, Suresh V. [NSF Cooling Technologies Research Center, School of Mechanical Engineering, Purdue University, 585 Purdue Mall, West Lafayette, IN 47907 (United States)

    2009-11-15

    This paper explores the feasibility of using electrostatically actuated diaphragm compressors in a miniature-scale refrigeration system for electronics cooling. A previously developed experimentally validated analytical model for the diaphragm compressor is used in conjunction with an optimization approach to determine the required dimensions for the compressor. The analysis reveals that the pressure rise and volume flow rate required for the electronics cooling application are not achieved using a single compressor because of material property limitations. A three-dimensional array of compressors is proposed instead with which the cooling requirements and the size restrictions for electronics cooling applications may be simultaneously satisfied. (author)

  9. Miniaturized high-precision piezo driven two axes stepper goniometer.

    Science.gov (United States)

    Zhong, H; Schwarz, A; Wiesendanger, R

    2014-04-01

    A miniaturized inertial stepper goniometer with two orthogonal axes (θ and φ axes) has been realized using four shear piezo based actuators arranged in a tetrahedral configuration tangent with a polished sapphire spherical rotor. The measured sensitivity is about 11.5 microdegree (μ°) per Volt. The smallest angular step size, achieved with a minimal peak-to-peak voltage Upp of 200 V is about 0.6 millidegree (m°). The crosstalk between both axes is below 10%. Our specific design is used to accurately position a glass fiber, but the concept can be utilized for many different applications as well.

  10. Miniaturized GC/MS instrumentation for in situ measurements: micro gas chromatography coupled with miniature quadrupole array and paul ion trap mass spectrometers

    Science.gov (United States)

    Holland, P.; Chutjian, A.; Darrach, M.; Orient, O.

    2002-01-01

    Miniaturized chemical instrumentation is needed for in situ measurements in planetary exploration and other spaceflight applications where factors such as reduction in payload requirements and enhanced robustness are important. In response to this need, we are 'continuing to develop miniaturized GC/MS instrumentation which combines chemical separations by gas chromatography (GC) with mass spectrometry (MS) to provide positive identification of chemical compounds in complex mixtures of gases, such as those found in the International Space Station's cabin atmosphere. Our design approach utilizes micro gas chromatography components coupled with either a miniature quadrupole mass spectrometer array (QMSA) or compact, high-resolution Paul ion trap.

  11. Radiological evaluation of spontaneous pneumoperitoneum

    International Nuclear Information System (INIS)

    Kim, H. S.; Kim, J. D.; Rhee, H. S.

    1982-01-01

    112 cases of spontaneous penumoperitoneum, the causes of which were confirmed by clinical and surgical procedure at Presbyterian Medical Center from January, 1977 to July, 1981 were reviewed radiologically. The results were as follows: 1. Perforation of duodenal ulcer (46/112: 41.1%), stomach ulcer (22/112: 19.6%), and stomach cancer (11/112: 9.8%) were the three most common causes of spontaneous penumoperitoneum. These were 70.5% of all causes. 2. The most common site of free gas was both subdiaphragmatic areas (46: 41.1%). Others were Rt. subdiaphragmatic only (31: 27.7%), both subdiaphragmatic with subhepatic (16: 14.3%), Rt. subdiaphragmatic with subhepatic (7: 6.2%), Rt. subdiaphragmatic only (5: 4.4%), diffuse in abdomen (4: 3.6%), and subhepatic only (3: 2.7%). So 92.0% (103/112) were located in RUQ. 3. The radiological shape of free gas was classified: crescent (52: 46.4%) of small amount; half-moon (21: 18.8%) of moderate amount; large or diffuse (39: 34.8%) of large amount.4. The age between 31 and 60 occupied 69.1% (77/112), and male was predominant (5.2 times). 5. The patient's position showing free air most frequently was erect

  12. 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.

  13. Spontaneity of communication in individuals with autism.

    Science.gov (United States)

    Chiang, Hsu-Min; Carter, Mark

    2008-04-01

    This article provides an examination of issues related to spontaneity of communication in children with autism. Deficits relating to spontaneity or initiation are frequently reported in individuals with autism, particularly in relation to communication and social behavior. Nevertheless, spontaneity is not necessarily clearly conceptualized or measured. Several approaches to conceptualization of communicative spontaneity are examined with a particular focus on the continuum model and how it might be practically applied. A range of possible explanations for deficits in spontaneity of communication in children with autism is subsequently explored, including external factors (highly structured teaching programs, failure to systematically instruct for spontaneity) and intrinsic characteristics (intellectual disability, stimulus overselectivity, weak central coherence). Possible implications for future research are presented.

  14. 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.

  15. 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.

  16. Spontaneous cryptococcal peritonitis in cirrhotic patients.

    Directory of Open Access Journals (Sweden)

    Sungkanuparph S

    2002-07-01

    Full Text Available Spontaneous bacterial peritonitis is a common complication in patients with cirrhosis and ascites. However, spontaneous peritonitis caused by Cryptococcus neoformans is uncommon. Delayed diagnosis of cryptococcal peritonitis often results in death. We describe three cases of spontaneous cryptococcal peritonitis in patients with decompensated cirrhosis. One case had associated symptomatic human immunodeficiency virus infection. Clinical awareness of this entity may lead to the early diagnosis and proper treatment.

  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. Spontaneous renal hematoma - a case report

    International Nuclear Information System (INIS)

    Obrzut, M.; Obrzut, M.; Homa, J.; Obrzut, B.

    2006-01-01

    Spontaneous pararenal hematoma is a rare pathology most frequently coexisting with renal tumours, vascular anomalies and inflammatory processes. In some cases one cannot establish its etiology. The paper describes a case of a 58-year-old man with a spontaneous pararenal hematoma and presents a diagnostic algorithm. Ultrasonography and CT play an important role in diagnostics of spontaneous pararenal haemorrhages. These methods enable a precise evaluation of size and location of hematoma and its evolution. (author)

  19. 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)

  20. Miniature in vivo robot for laparoendoscopic single-site surgery.

    Science.gov (United States)

    Dolghi, Oleg; Strabala, Kyle W; Wortman, Tyler D; Goede, Matthew R; Farritor, Shane M; Oleynikov, Dmitry

    2011-10-01

    The aim of this study was to develop a multidexterous robot capable of generating the required forces and speeds to perform surgical tasks intra-abdominally. Current laparoscopic surgical robots are expensive, bulky, and fundamentally constrained by a small entry incision. A new approach to minimally invasive surgery places the robot completely within the patient. Miniature in vivo robots may allow surgeons to overcome current laparoscopic constraints such as dexterity, orientation, and visualization. A collaborative research group from the Department of Surgery at the University of Nebraska Medical Center and the College of Engineering at the University of Nebraska-Lincoln designed and built a surgical robot prototype capable of performing specific surgical tasks within the peritoneal cavity. The basic robotic design consists of two arms each connected to a central body. Each arm has three degrees of freedom and rotational shoulder and elbow joints. This combination allows a surgeon to grasp, manipulate, cauterize, and perform intracorporeal suturing. The robot's workspace is a hollow hemisphere with an inner radius of 75 mm and an outer radius of 205 mm. Its versatility was demonstrated in four procedures performed in a porcine model: cholecystectomy, partial colectomy, abdominal exploration, and intracorporeal suturing. Miniature in vivo robots have the potential to address the limitations of using articulated instrumentation to perform advanced laparoscopic surgical procedures. Once inserted into the peritoneal cavity, the robot provides a stable platform for visualization with sufficient dexterity and speed to perform surgical tasks from multiple orientations and workspaces.

  1. Glass, plastic, and semiconductors: packaging techniques for miniature optoelectronic components

    Science.gov (United States)

    Pocha, Michael D.; Garrett, Henry E.; Patel, Rajesh R.; Jones, Leslie M., III; Larson, Michael C.; Emanuel, Mark A.; Bond, Steven W.; Deri, Robert J.; Drayton, R. F.; Petersen, Holly E.; Lowry, Mark E.

    2000-03-01

    At Lawrence Livermore National Laboratory, we have extensive experience with the design and development of miniature photonic systems which require novel packaging schemes. Over the years we have developed silicon micro-optical benches to serve as a stable platform for precision mounting of optical and electronic components. We have developed glass ball lenses that can be fabricated in-situ on the microbench substrate. We have modified commercially available molded plastic fiber ribbon connectors (MT) and added thin film multilayer semiconductor coatings to create potentially low-cost wavelength combiners and wavelength selective filters. We have fabricated both vertical-cavity and in-plane semiconductor lasers and amplifiers, and have packaged these and other components into several miniature photonics systems. For example, we have combined the silicon optical bench with standard electronic packaging techniques and our custom-made wavelength-selective filters to develop a four-wavelength wavelength-division-multiplexing transmitter module mounted in a standard 120-pin ceramic PGA package that couples light from several vertical-cavity-surface-emitting-laser arrays into one multimode fiber-ribbon array. The coupling loss can be as low as 2 dB, and the transmitters can be operated at over 1.25 GHz. While these systems were not designed for biomedical or environmental applications, the concepts and techniques are general and widely applicable.

  2. A miniaturized UWB antenna for implantable data telemetry.

    Science.gov (United States)

    Haas, Michael; Schweizer, Benedikt; Anders, Jens; Ortmanns, Maurits

    2017-07-01

    This paper presents a miniaturized impulse radio ultra-wideband (IR-UWB) antenna which is designed for transcutaneous, short-distance data communication used in multichannel neural recording. In these systems, with the increasing number of recording channels, data rates of 10-100 Mbit/s must be transmitted with very limited power and area. Therefore, the antennas are designed as planar, ellipsoidal dipoles on a high permittivity substrate with ε r = 10.2 to achieve high radiation efficiency with small physical size. In order to increase the robustness against misalignment, a circularly polarized antenna is used at the external receiver unit, reducing the signal power variation under angular misalignment. For the transmitting antenna a miniaturized prototype with an integrated pulse generator was designed on a round shaped PCB with a diameter of only 14mm. Measurements through porcine skin in the frequency domain show an attenuation of less than 30dB in the intended frequency band between 6 and 8.5GHz. Additional evaluations in the time domain prove possible pulse repetition rates of up to 100MHz at a transmission distance of 1.5cm.

  3. Miniature near-infrared (NIR) spectrometer engine for handheld applications

    Science.gov (United States)

    O'Brien, Nada A.; Hulse, Charles A.; Friedrich, Donald M.; Van Milligen, Fred J.; von Gunten, Marc K.; Pfeifer, Frank; Siesler, Heinz W.

    2012-06-01

    While substantial progress has been made recently towards the miniaturization of Raman, mid-infrared (IR), and near-infrared (NIR) spectrometers, there remains continued interest from end-users and product developers in pushing the technology envelope toward even smaller and lower cost analyzers. The potential of these instruments to revolutionize on-site and on-line applications can only be realized if the reduction in size does not compromise performance of the spectrometer beyond the practical need of a given application. In this paper, the working principle of a novel, extremely miniaturized NIR spectrometer will be presented. The ultra-compact spectrometer relies on thin-film linear variable filter (LVF) technology for the light dispersing element. We will also report on an environmental study whereby the contamination of soil by oil is determined quantitatively in the range of 0-12% by weight of oil contamination. The achieved analytical results will be discussed in terms of the instrument's competitiveness and suitability for on-site and in-the-field measurements.

  4. Spectroscopic investigations of Bourdichon miniatures: masterpieces of light and color.

    Science.gov (United States)

    Burgio, Lucia; Clark, Robin J H; Hark, Richard R; Rumsey, Mike S; Zannini, Carlotta

    2009-06-01

    Metallic bismuth, pyrite (FeS2), and specular hematite (Fe2O3) were found to have been used extensively on two miniatures taken from the Book of Hours of Louis XII by Jean Bourdichon, painter at the Royal Court of France between the end of the 15th and the beginning of the 16th centuries. These unusual materials were identified, together with thirteen other more traditional pigments and dyes, by Raman microscopy and X-ray fluorescence. Pyrite was found in many areas, suggesting that it may have been deliberately added as a pigment. The luminary quality of both miniatures was enhanced by the extensive use of shell gold throughout, but other less common materials such as specular hematite and mosaic gold were also utilized. Metallic bismuth was used, alone or in admixture with other pigments, to create a soft gray color. Its identification as a paint material was complemented by the study of the optical and visual properties of standard samples of metallic bismuth and several bismuth compounds. Evidence for the use of a bismuth pencil was also found.

  5. 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.

  6. Potentials and limitations of miniaturized calorimeters for bioprocess monitoring.

    Science.gov (United States)

    Maskow, Thomas; Schubert, Torsten; Wolf, Antje; Buchholz, Friederike; Regestein, Lars; Buechs, Jochen; Mertens, Florian; Harms, Hauke; Lerchner, Johannes

    2011-10-01

    In theory, heat production rates are very well suited for analysing and controlling bioprocesses on different scales from a few nanolitres up to many cubic metres. Any bioconversion is accompanied by a production (exothermic) or consumption (endothermic) of heat. The heat is tightly connected with the stoichiometry of the bioprocess via the law of Hess, and its rate is connected to the kinetics of the process. Heat signals provide real-time information of bioprocesses. The combination of heat measurements with respirometry is theoretically suited for the quantification of the coupling between catabolic and anabolic reactions. Heat measurements have also practical advantages. Unlike most other biochemical sensors, thermal transducers can be mounted in a protected way that prevents fouling, thereby minimizing response drifts. Finally, calorimetry works in optically opaque solutions and does not require labelling or reactants. It is surprising to see that despite all these advantages, calorimetry has rarely been applied to monitor and control bioprocesses with intact cells in the laboratory, industrial bioreactors or ecosystems. This review article analyses the reasons for this omission, discusses the additional information calorimetry can provide in comparison with respirometry and presents miniaturization as a potential way to overcome some inherent weaknesses of conventional calorimetry. It will be discussed for which sample types and scientific question miniaturized calorimeter can be advantageously applied. A few examples from different fields of microbiological and biotechnological research will illustrate the potentials and limitations of chip calorimetry. Finally, the future of chip calorimetry is addressed in an outlook.

  7. Miniature high-performance infrared spectrometer for space applications

    Science.gov (United States)

    Kruzelecky, Roman V.; Haddad, Emile; Wong, Brian; Lafrance, Denis; Jamroz, Wes; Ghosh, Asoke K.; Zheng, Wanping; Phong, Linh

    2017-11-01

    Infrared spectroscopy probes the characteristic vibrational and rotational modes of chemical bonds in molecules to provide information about both the chemical composition and the bonding configuration of a sample. The significant advantage of the Infrared spectral technique is that it can be used with minimal consumables to simultaneously detect a large variety of chemical and biochemical species with high chemical specificity. To date, relatively large Fourier Transform (FT-IR) spectrometers employing variations of the Michelson interferometer have been successfully employed in space for various IR spectroscopy applications. However, FT-IR systems are mechanically complex, bulky (> 15 kg), and require considerable processing. This paper discusses the use of advanced integrated optics and smart optical coding techniques to significantly extend the performance of miniature IR spectrometers by several orders of magnitude in sensitivity. This can provide the next generation of compact, high-performance IR spectrometers with monolithically integrated optical systems for robust optical alignment. The entire module can weigh under 3 kg to minimize the mass penalty for space applications. Miniaturized IR spectrometers are versatile and very convenient for small and micro satellite based missions. They can be dedicated to the monitoring of the CO2 in an Earth Observation mission, to Mars exobiology exploration, as well as to vital life support in manned space system; such as the cabin air quality and the quality of the recycled water supply.

  8. Generation of induced pluripotent stem cells (iPSCs from a hypertrophic cardiomyopathy patient with the pathogenic variant p.Val698Ala in beta-myosin heavy chain (MYH7 gene

    Directory of Open Access Journals (Sweden)

    Samantha Barratt Ross

    2017-04-01

    Full Text Available Induced pluripotent stem cells (iPSCs were generated from peripheral blood mononuclear cells (PBMCs isolated from the whole blood of a 43-year-old male with hypertrophic cardiomyopathy (HCM who carries the pathogenic variant p.Val698Ala in beta-myosin heavy chain (MYH7. Patient-derived PBMCs were reprogrammed using non-integrative episomal vectors containing reprogramming factors OCT4, SOX2, LIN28, KLF4 and L-MYC. iPSCs were shown to express pluripotent markers, have trilineage differentiation potential, carry the pathogenic MYH7 variant p.Val698Ala, have a normal karyotype and no longer carry the episomal reprogramming vector. This line is useful for studying the link between variants in MYH7 and the pathogenesis of HCM.

  9. Generation of a human induced pluripotent stem cell (iPSC line from a 51-year-old female with attention-deficit/hyperactivity disorder (ADHD carrying a duplication of SLC2A3

    Directory of Open Access Journals (Sweden)

    Charline Jansch

    2018-04-01

    Full Text Available Fibroblasts were isolated from a skin biopsy of a clinically diagnosed 51-year-old female attention-deficit/hyperactivity disorder (ADHD patient carrying a duplication of SLC2A3, a gene encoding neuronal glucose transporter-3 (GLUT3. Patient fibroblasts were infected with Sendai virus, a single-stranded RNA virus, to generate transgene-free human induced pluripotent stem cells (iPSCs. SLC2A3-D2-iPSCs showed expression of pluripotency-associated markers, were able to differentiate into cells of the three germ layers in vitro and had a normal female karyotype. This in vitro cellular model can be used to study the role of risk genes in the pathogenesis of ADHD, in a patient-specific manner.

  10. Integration-free T cell-derived human induced pluripotent stem cells (iPSCs from a patient with recessive dystrophic epidermolysis bullosa (RDEB carrying two compound heterozygous mutations in the COL7A1 gene

    Directory of Open Access Journals (Sweden)

    Munenari Itoh

    2016-07-01

    Full Text Available Expanded human T cells from a Japanese female with recessive dystrophic epidermolysis bullosa (RDBE were used to generate integration-free induced pluripotent stem cells (iPSCs by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp. The authenticity of established iPSC line, RDEB-iPSC26, was confirmed by the expressions of stem cell markers and the differentiation capability into three germ layer. RDEB-iPSC26 may be a useful cell resource for the establishment of in vitro RDEB modeling and the study for developing gene and cell therapy.

  11. Terrestrialization, miniaturization and rates of diversification in African frogs (Anura: Phrynobatrachidae)

    Science.gov (United States)

    Terrestrialization, the evolution of non-aquatic oviposition, and miniaturization, the evolution of tiny adult body size, have been identified as a key features in the evolution of modern amphibians. This study examines anuran terrestrialization and miniaturization in a phylogenetic context to deter...

  12. 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 scre...

  13. 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 ...

  14. Biomarkers of spontaneous preterm birth

    DEFF Research Database (Denmark)

    Polettini, Jossimara; Cobo, Teresa; Kacerovsky, Marian

    2017-01-01

    predictors of pregnancy outcome. This systematic review was conducted to synthesize the knowledge on PTB biomarkers identified using multiplex analysis. Three electronic databases (PubMed, EMBASE and Web of Science) were searched for studies in any language reporting the use of multiplex assays for maternal......Despite decades of research on risk indicators of spontaneous preterm birth (PTB), reliable biomarkers are still not available to screen or diagnose high-risk pregnancies. Several biomarkers in maternal and fetal compartments have been mechanistically linked to PTB, but none of them are reliable......) followed by MIP-1β, GM-CSF, Eotaxin, and TNF-RI (two studies) were reported more than once in maternal serum. However, results could not be combined due to heterogeneity in type of sample, study population, assay, and analysis methods. By this systematic review, we conclude that multiplex assays...

  15. Spontaneous Strategies in Innovation Networks

    DEFF Research Database (Denmark)

    Plesner, Ursula; Husted, Emil Krastrup

    and a site ontology, we show how physical sites and objects become constitutive of the inside of virtual worlds through innovation processes. This argument is in line with ANT’s perspective on strategy, where sites and objects are considered a strategically relevant resource in the innovation process...... of materiality in relation to the organization and structuring of virtual worlds. We examine various innovation processes in five Danish entrepreneurial companies where actors continuously struggle to stabilize virtual worlds as platforms for professional communication. With inspiration from actor-network theory....... Empirically, the analysis is founded on descriptive accounts from the five entrepreneurs. By highlighting the spontaneous strategies described by actors, we show how sites and objects are actively used as an element in their strategy, and also how the sites and objects end up facilitating new ways of thinking...

  16. 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

    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 plu...... of genetically corrected iPSCs from a pre-symptomatic carrier of the R406W mutation in the MAPT-gene....

  17. 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

    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 plu...... of genetically corrected iPSCs from a 59-year-old female FTD-17 patient carrying an R406W mutation in the MAPT-gene....

  18. Recurrent spontaneous attacks of dizziness.

    Science.gov (United States)

    Lempert, Thomas

    2012-10-01

    This article describes the common causes of recurrent vertigo and dizziness that can be diagnosed largely on the basis of history. Ninety percent of spontaneous recurrent vertigo and dizziness can be explained by six disorders: (1) Ménière disease is characterized by vertigo attacks, lasting 20 minutes to several hours, with concomitant hearing loss, tinnitus, and aural fullness. Aural symptoms become permanent during the course of the disease. (2) Attacks of vestibular migraine may last anywhere from minutes to days. Most patients have a previous history of migraine headaches, and many experience migraine symptoms during the attack. (3) Vertebrobasilar TIAs affect older adults with vascular risk factors. Most attacks last less than 1 hour and are accompanied by other symptoms from the posterior circulation territory. (4) Vestibular paroxysmia is caused by vascular compression of the eighth cranial nerve. It manifests itself with brief attacks of vertigo that recur many times per day, sometimes with concomitant cochlear symptoms. (5) Orthostatic hypotension causes brief episodes of dizziness lasting seconds to a few minutes after standing up and is relieved by sitting or lying down. In older adults, it may be accompanied by supine hypertension. (6) Panic attacks usually last minutes, occur in specific situations, and are accompanied by choking, palpitations, tremor, heat, and anxiety. Less common causes of spontaneous recurrent vertigo and dizziness include perilymph fistula, superior canal dehiscence, autoimmune inner ear disease, otosclerosis, cardiac arrhythmia, and medication side effects. Neurologists need to venture into otolaryngology, internal medicine, and psychiatry to master the differential diagnosis of recurrent dizziness.

  19. Crows spontaneously exhibit analogical reasoning.

    Science.gov (United States)

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Modeling Neural Crest Induction, Melanocyte Specification, and Disease-Related Pigmentation Defects in hESCs and Patient-Specific iPSCs

    Directory of Open Access Journals (Sweden)

    Yvonne Mica

    2013-04-01

    Full Text Available Melanocytes are pigment-producing cells of neural crest (NC origin that are responsible for protecting the skin against UV irradiation. Pluripotent stem cell (PSC technology offers a promising approach for studying human melanocyte development and disease. Here, we report that timed exposure to activators of WNT, BMP, and EDN3 signaling triggers the sequential induction of NC and melanocyte precursor fates under dual-SMAD-inhibition conditions. Using a SOX10::GFP human embryonic stem cell (hESC reporter line, we demonstrate that the temporal onset of WNT activation is particularly critical for human NC induction. Subsequent maturation of hESC-derived melanocytes yields pure populations that match the molecular and functional properties of adult melanocytes. Melanocytes from Hermansky-Pudlak syndrome and Chediak-Higashi syndrome patient-specific induced PSCs (iPSCs faithfully reproduce the ultrastructural features of disease-associated pigmentation defects. Our data define a highly specific requirement for WNT signaling during NC induction and enable the generation of pure populations of human iPSC-derived melanocytes for faithful modeling of pigmentation disorders.

  1. 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.

  2. Stabiliteit spontane taal bij chronische milde afasie

    NARCIS (Netherlands)

    Wolthuis, Nienke; Mendez Orellana, Carolina; Nouwens, Femke; Jonkers, Roel; Visch-Brink, Evy; Bastiaanse, Roelien

    2014-01-01

    In aphasia, an analysis of spontaneous speech provides opportunities to establish the linguistic and communicative abilities, to create suitable therapy plans and to measure language progress. The current study investigated the stability of spontaneous speech within an interview of ten mild aphasic

  3. Spontaneously broken abelian gauge invariant supersymmetric model

    International Nuclear Information System (INIS)

    Mainland, G.B.; Tanaka, K.

    A model is presented that is invariant under an Abelian gauge transformation and a modified supersymmetry transformation. This model is broken spontaneously, and the interplay between symmetry breaking, Goldstone particles, and mass breaking is studied. In the present model, spontaneously breaking the Abelian symmetry of the vacuum restores the invariance of the vacuum under a modified supersymmetry transformation. (U.S.)

  4. Spontaneous Achilles tendon rupture in alkaptonuria | Mohammed ...

    African Journals Online (AJOL)

    Spontaneous Achilles tendon ruptures are uncommon. We present a 46-year-old man with spontaneous Achilles tendon rupture due to ochronosis. To our knowledge, this has not been previously reported in Sudan literature. The tendon of the reported patient healed well after debridement and primary repairs.

  5. Spontaneous rupture of choledochal cyst: case report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ho Seob; Nam, Kyung Jin; Lee, Jin Hwa; Kim, Chan Sung; Choi, Jong Cheol; Oh, Jong Young [Dong-a University College of Medicine, Pusan (Korea, Republic of)

    2002-11-01

    Spontaneous rupture of a choledochal cyst leading to biliary peritonitis is a rare complication which can be fatal if not promptly diagnosed. The authors report the ultrasound and CT findings of two cases of spontaneous choledochal cystic rupture and the biliary peritonitis which ensued.

  6. Spontaneity and Equilibrium II: Multireaction Systems

    Science.gov (United States)

    Raff, Lionel M.

    2014-01-01

    The thermodynamic criteria for spontaneity and equilibrium in multireaction systems are developed and discussed. When N reactions are occurring simultaneously, it is shown that G and A will depend upon N independent reaction coordinates, ?a (a = 1,2, ..., N), in addition to T and p for G or T and V for A. The general criteria for spontaneity and…

  7. Ultra-low noise miniaturized neural amplifier with hardware averaging.

    Science.gov (United States)

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

    2015-08-01

    Peripheral nerves carry neural signals that could be used to control hybrid bionic systems. Cuff electrodes provide a robust and stable interface but the recorded signal amplitude is small (noise of less than 1 μVrms for a useful signal-to-noise ratio (SNR). Flat interface nerve electrode (FINE) contacts alone generate thermal noise of at least 0.5 μVrms therefore the amplifier should add as little noise as possible. Since mainstream neural amplifiers have a baseline noise of 2 μVrms or higher, novel designs are required. Here we apply the concept of hardware averaging to nerve recordings obtained with cuff electrodes. An optimization procedure is developed to minimize noise and power simultaneously. The novel design was based on existing neural amplifiers (Intan Technologies, LLC) and is validated with signals obtained from the FINE in chronic dog experiments. We showed that hardware averaging leads to a reduction in the total recording noise by a factor of 1/√N or less depending on the source resistance. Chronic recording of physiological activity with FINE using the presented design showed significant improvement on the recorded baseline noise with at least two parallel operation transconductance amplifiers leading to a 46.1% reduction at N = 8. The functionality of these recordings was quantified by the SNR improvement and shown to be significant for N = 3 or more. The present design was shown to be capable of generating noise when connected to a FINE placed on the sciatic nerve of an awake animal. An algorithm was introduced to find the value of N that can minimize both the power consumption and the noise in order to design a miniaturized ultralow-noise neural amplifier. These results demonstrate the efficacy of hardware averaging on noise improvement for neural recording with cuff electrodes, and can accommodate the presence of high source impedances that are associated with the miniaturized contacts and the high channel count in electrode arrays. This

  8. Ultra-low noise miniaturized neural amplifier with hardware averaging

    Science.gov (United States)

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

    2015-08-01

    Objective. Peripheral nerves carry neural signals that could be used to control hybrid bionic systems. Cuff electrodes provide a robust and stable interface but the recorded signal amplitude is small (noise of less than 1 μVrms for a useful signal-to-noise ratio (SNR). Flat interface nerve electrode (FINE) contacts alone generate thermal noise of at least 0.5 μVrms therefore the amplifier should add as little noise as possible. Since mainstream neural amplifiers have a baseline noise of 2 μVrms or higher, novel designs are required. Approach. Here we apply the concept of hardware averaging to nerve recordings obtained with cuff electrodes. An optimization procedure is developed to minimize noise and power simultaneously. The novel design was based on existing neural amplifiers (Intan Technologies, LLC) and is validated with signals obtained from the FINE in chronic dog experiments. Main results. We showed that hardware averaging leads to a reduction in the total recording noise by a factor of 1/√N or less depending on the source resistance. Chronic recording of physiological activity with FINE using the presented design showed significant improvement on the recorded baseline noise with at least two parallel operation transconductance amplifiers leading to a 46.1% reduction at N = 8. The functionality of these recordings was quantified by the SNR improvement and shown to be significant for N = 3 or more. The present design was shown to be capable of generating noise when connected to a FINE placed on the sciatic nerve of an awake animal. An algorithm was introduced to find the value of N that can minimize both the power consumption and the noise in order to design a miniaturized ultralow-noise neural amplifier. Significance. These results demonstrate the efficacy of hardware averaging on noise improvement for neural recording with cuff electrodes, and can accommodate the presence of high source impedances that are associated with the miniaturized contacts and

  9. 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

  10. Glutamate released spontaneously from astrocytes sets the threshold for synaptic plasticity.

    Science.gov (United States)

    Bonansco, Christian; Couve, Alejandro; Perea, Gertrudis; Ferradas, Carla Á; Roncagliolo, Manuel; Fuenzalida, Marco

    2011-04-01

    Astrocytes exhibit spontaneous calcium oscillations that could induce the release of glutamate as gliotransmitter in rat hippocampal slices. However, it is unknown whether this spontaneous release of astrocytic glutamate may contribute to determining the basal neurotransmitter release probability in central synapses. Using whole-cell recordings and Ca(2+) imaging, we investigated the effects of the spontaneous astrocytic activity on neurotransmission and synaptic plasticity at CA3-CA1 hippocampal synapses. We show here that the metabolic gliotoxin fluorocitrate (FC) reduces the amplitude of evoked excitatory postsynaptic currents and increases the paired-pulse facilitation, mainly due to the reduction of the neurotransmitter release probability and the synaptic potency. FC also decreased intracellular Ca(2+) signalling and Ca(2+) -dependent glutamate release from astrocytes. The addition of glutamine rescued the effects of FC over the synaptic potency; however, the probability of neurotransmitter release remained diminished. The blockage of group I metabotropic glutamate receptors mimicked the effects of FC on the frequency of miniature synaptic responses. In the presence of FC, the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N ',N '-tetra-acetate or group I metabotropic glutamate receptor antagonists, the excitatory postsynaptic current potentiation induced by the spike-timing-dependent plasticity protocol was blocked, and it was rescued by delivering a stronger spike-timing-dependent plasticity protocol. Taken together, these results suggest that spontaneous glutamate release from astrocytes contributes to setting the basal probability of neurotransmitter release via metabotropic glutamate receptor activation, which could be operating as a gain control mechanism that regulates the threshold of long-term potentiation. Therefore, endogenous astrocyte activity provides a novel non-neuronal mechanism that could be critical for transferring information in

  11. The (perceived) meaning of spontaneous thoughts.

    Science.gov (United States)

    Morewedge, Carey K; Giblin, Colleen E; Norton, Michael I

    2014-08-01

    Spontaneous thoughts, the output of a broad category of uncontrolled and inaccessible higher order mental processes, arise frequently in everyday life. The seeming randomness by which spontaneous thoughts arise might give people good reason to dismiss them as meaningless. We suggest that it is precisely the lack of control over and access to the processes by which they arise that leads people to perceive spontaneous thoughts as revealing meaningful self-insight. Consequently, spontaneous thoughts potently influence judgment. A series of experiments provides evidence supporting two hypotheses. First, we hypothesize that the more a thought is perceived to be spontaneous, the more it is perceived to provide meaningful self-insight. Participants perceived more spontaneous kinds of thought (e.g., intuition) to reveal greater self-insight than did more controlled kinds of thought in Study 1 (e.g., deliberation). In Studies 2 and 3, participants perceived thoughts with the same content and target to reveal greater self-insight when spontaneously rather than deliberately generated (i.e., childhood memories and impressions formed). Second, we hypothesize that the greater self-insight attributed to thoughts that are (perceived to be) spontaneous leads those thoughts to more potently influence judgment. Participants felt more sexually attracted to an attractive person whom they thought of spontaneously than deliberately in Study 4, and reported their commitment to a current romantic relationship would be more affected by the spontaneous rather than deliberate recollection of a good or bad experience with their romantic partner in Study 5. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  12. Sliding mode tracking control for miniature unmanned helicopters

    Directory of Open Access Journals (Sweden)

    Bin Xian

    2015-02-01

    Full Text Available A sliding mode control design for a miniature unmanned helicopter is presented. The control objective is to let the helicopter track some predefined velocity and yaw trajectories. A new sliding mode control design method is developed based on a linearized dynamic model. In order to facilitate the control design, the helicopter’s dynamic model is divided into two subsystems, such as the longitudinal-lateral and the heading-heave subsystem. The proposed controller employs sliding mode control technique to compensate for the immeasurable flapping angles’ dynamic effects and external disturbances. The global asymptotic stability (GAS of the closed-loop system is proved by the Lyapunov based stability analysis. Numerical simulations demonstrate that the proposed controller can achieve superior tracking performance compared with the proportional-integral-derivative (PID and linear-quadratic regulator (LQR cascaded controller in the presence of wind gust disturbances.

  13. Miniaturized, low power FGMOSFET radiation sensor and wireless dosimeter system

    KAUST Repository

    Arsalan, Muhammad

    2013-08-27

    A miniaturized floating gate (FG) MOSFET radiation sensor system is disclosed, The sensor preferably comprises a matched pair of sensor and reference FGMOSFETs wherein the sensor FGMOSFET has a larger area floating gate with an extension over a field oxide layer, for accumulation of charge and increased sensitivity. Elimination of a conventional control gate and injector gate reduces capacitance, and increases sensitivity, and allows for fabrication using standard low cost CMOS technology. A sensor system may be provided with integrated signal processing electronics, for monitoring a change in differential channel current I.sub.D, indicative of radiation dose, and an integrated negative bias generator for automatic pre-charging from a low voltage power source. Optionally, the system may be coupled to a wireless transmitter. A compact wireless sensor System on Package solution is presented, suitable for dosimetry for radiotherapy or other biomedical applications.

  14. Miniature Release Mechanism or Diminutive Assembly for Nanosatellite Deployables (DANY)

    Science.gov (United States)

    Santos Soto, Luis H. (Inventor); Hesh, Scott V. (Inventor); Hudeck, John D. (Inventor)

    2017-01-01

    Miniature release mechanisms constrain objects, such as deployables during the launch of space vehicles, such as small satellites and nanosatellites, and enable the release of the objects once a desired destination is reached by the space vehicle. Constraint and release of the objects are achieved by providing a secure threaded interface that may be released by the release mechanisms. The release mechanisms include a housing structure; a release block can include a threaded interface; one or more retracting pins; one or more release springs; a breakable link, such as a plastic link; a cable harness clamp; and a circuit board. The release mechanism can be 0.1875 inches (approximately 4.8 mm) thick.

  15. Miniature electron bombardment evaporation source: evaporation rate measurement

    International Nuclear Information System (INIS)

    Nehasil, V.; Masek, K.; Matolin, V.; Moreau, O.

    1997-01-01

    Miniature electron beam evaporation sources which operate on the principle of vaporization of source material, in the form of a tip, by electron bombardment are produced by several companies specialized in UHV equipment. These sources are used primarily for materials that are normally difficult to deposit due to their high evaporation temperature. They are appropriate for special applications such as heteroepitaxial thin film growth requiring a very low and well controlled deposition rate. A simple and easily applicable method of evaporation rate control is proposed. The method is based on the measurement of ion current produced by electron bombardment of evaporated atoms. The absolute evaporation flux values were measured by means of the Bayard-Alpert ion gauge, which enabled the ion current vs evaporation flux calibration curves to be plotted. (author). 1 tab., 4 figs., 6 refs

  16. A Miniaturized Nickel Oxide Thermistor via Aerosol Jet Technology

    Directory of Open Access Journals (Sweden)

    Chia Wang

    2017-11-01

    Full Text Available In this study, a miniaturized thermistor sensor was produced using the Aerosol Jet printing process for temperature sensing applications. A nickel oxide nanoparticle ink with a large temperature coefficient of resistance was fabricated. The thermistor was printed with a circular NiO thin film in between the two parallel silver conductive tracks on a cutting tool insert. The printed thermistor, which has an adjustable dimension with a submillimeter scale, operates over a range of 30–250 °C sensitively (B value of ~4310 K without hysteretic effects. Moreover, the thermistor may be printed on a 3D surface through the Aerosol Jet printing process, which has increased capability for wide temperature-sensing applications.

  17. Miniature gamma-ray camera for tumor localization

    International Nuclear Information System (INIS)

    Lund, J.C.; Olsen, R.W.; James, R.B.; Cross, E.

    1997-08-01

    The overall goal of this LDRD project was to develop technology for a miniature gamma-ray camera for use in nuclear medicine. The camera will meet a need of the medical community for an improved means to image radio-pharmaceuticals in the body. In addition, this technology-with only slight modifications-should prove useful in applications requiring the monitoring and verification of special nuclear materials (SNMs). Utilization of the good energy resolution of mercuric iodide and cadmium zinc telluride detectors provides a means for rejecting scattered gamma-rays and improving the isotopic selectivity in gamma-ray images. The first year of this project involved fabrication and testing of a monolithic mercuric iodide and cadmium zinc telluride detector arrays and appropriate collimators/apertures. The second year of the program involved integration of the front-end detector module, pulse processing electronics, computer, software, and display

  18. Coming home - Bally’s miniature phrenological specimens

    Directory of Open Access Journals (Sweden)

    Dr Alice Cliff

    2014-03-01

    Full Text Available The arrival of William Bally’s set of miniature phrenological specimens in Manchester for the Wellcome Collection exhibition Brains: The Mind as Matter (26 July 2013 – 4 January 2014 was an ideal time to reassess the mysteries of its production – was it made in Manchester or Dublin? In what context was it produced? Phrenology – the study of the shape and contours of the skull to determine mental faculties – has received attention from historians. But the origin and context of this object, although long part of the canon of 19th-century phrenology, has never been fully explored. Close inspection of the object has enabled analysis of its place in the career of its maker, and its significance today as evidence of the role of material culture in the practice of 19th-century phrenology.

  19. Impact of Microgroove Shape on Flat Miniature Heat Pipe Efficiency

    Directory of Open Access Journals (Sweden)

    François Ternet

    2018-01-01

    Full Text Available Miniature heat pipes are considered to be an innovative solution able to dissipate high heat with low working fluid fill charge, provide automatic temperature control, and operate with minimum energy consumption and low noise levels. A theoretical analysis on heat pipe thermal performance using Deionized water or n-pentane as the working fluid has been carried out. Analysis on the maximum heat and capillary limitation is conducted for three microgroove cross sections: rectangular, triangular, and trapezoidal. The effect of microgroove height and width, effective length, trapezoidal microgroove inclination angle, and microgroove shape on heat pipe performance is analysed. Theoretical and experimental investigations of the heat pipes’ heat transport limitations and thermal resistances are conducted.

  20. Sorption-cooled continuous miniature dilution refrigeration for astrophysical applications

    Science.gov (United States)

    May, Andrew J.; Calisse, Paolo G.; Coppi, Gabriele; Haynes, Vic; Martinis, Lorenzo; McCulloch, Mark A.; Melhuish, Simon J.; Piccirillo, Lucio

    2016-07-01

    A progress report is provided on the development of a tiltable continuous miniature dilution refrigerator and associated 3He/4He sorption coolers. These systems are currently being developed to provide sub-Kelvin cooling of the bolometer arrays for several ground- and balloon-based experiments which aim to measure the polarization of the Cosmic Microwave Background (QUBIC, LSPE and POLARBEAR-2). The novel tiltable miniaturised system benefits from a lack of external circulation pumps and a mechanically simple design. The condenser of the twin-pumped recirculating diluter is cooled continuously by two 3He/4He sorption coolers. The sorption pumps are operated by convective heat switches. The dilution unit features a thermally separated mixing chamber, still and step heat exchangers. The designs and analyses of both the sorption coolers and the diluter are reported; both systems have been manufactured and are presently under test.

  1. Miniature gamma-ray camera for tumor localization

    Energy Technology Data Exchange (ETDEWEB)

    Lund, J.C.; Olsen, R.W.; James, R.B.; Cross, E. [and others

    1997-08-01

    The overall goal of this LDRD project was to develop technology for a miniature gamma-ray camera for use in nuclear medicine. The camera will meet a need of the medical community for an improved means to image radio-pharmaceuticals in the body. In addition, this technology-with only slight modifications-should prove useful in applications requiring the monitoring and verification of special nuclear materials (SNMs). Utilization of the good energy resolution of mercuric iodide and cadmium zinc telluride detectors provides a means for rejecting scattered gamma-rays and improving the isotopic selectivity in gamma-ray images. The first year of this project involved fabrication and testing of a monolithic mercuric iodide and cadmium zinc telluride detector arrays and appropriate collimators/apertures. The second year of the program involved integration of the front-end detector module, pulse processing electronics, computer, software, and display.

  2. Yield stress determination from miniaturized disk bend test data

    International Nuclear Information System (INIS)

    Sohn, D.S.; Kohse, G.; Harling, O.K.

    1985-04-01

    Methodology for testing 3.0 mm diameter by 0.25 mm thick disks by bending in a punch and die has been described previously. This paper describes the analysis of load/deflection data from such miniaturized disk bend tests (MDBT) using a finite element simulation. Good simulation has been achieved up to a point just beyond the predominantly elastic response, linear initial region. The load at which deviation from linearity begins has been found to correlate with yield stress, and yield stress has been successfully extracted from disk bend tests of a number of known materials. Although finite element codes capable of dealing with large strains and large rotations have been used, simulation of the entire load/deflection curve up to fracture of the specimen has not yet been achieved

  3. Miniature Bioreactor System for Long-Term Cell Culture

    Science.gov (United States)

    Gonda, Steve R.; Kleis, Stanley J.; Geffert, Sandara K.

    2010-01-01

    A prototype miniature bioreactor system is designed to serve as a laboratory benchtop cell-culturing system that minimizes the need for relatively expensive equipment and reagents and can be operated under computer control, thereby reducing the time and effort required of human investigators and reducing uncertainty in results. The system includes a bioreactor, a fluid-handling subsystem, a chamber wherein the bioreactor is maintained in a controlled atmosphere at a controlled temperature, and associated control subsystems. The system can be used to culture both anchorage-dependent and suspension cells, which can be either prokaryotic or eukaryotic. Cells can be cultured for extended periods of time in this system, and samples of cells can be extracted and analyzed at specified intervals. By integrating this system with one or more microanalytical instrument(s), one can construct a complete automated analytical system that can be tailored to perform one or more of a large variety of assays.

  4. Piezo-based miniature high resolution stabilized gimbal

    Science.gov (United States)

    Karasikov, Nir; Peled, Gal; Yasinov, Roman; Yetkariov, Rita

    2016-05-01

    Piezo motors are characterized by higher mechanical power density, fast response and direct drive. These features are beneficial for miniature gimbals. A gimbal based on such motors was developed. Diameter is 58 mm, weight is 190 grams. The gimbal carries two cameras: a Flir Quark and an HD day camera. The dynamic performance is as high as 3 rad/sec velocity and 100 rad/secΛ2 acceleration. A two axes stabilization algorithm was developed, yielding 80 micro radian stabilization. Further, a panoramic image capture, at a rate of six stabilized field of views per second, was developed. The manuscript reviews the gimbal structure and open architecture, allowing adaptation to other cameras (SWIR etc.), the control algorithm and presents experimental results of stabilization and of panoramic views taken on a vibration platform and on a UAV.

  5. In vivo demonstration of surgical task assistance using miniature robots.

    Science.gov (United States)

    Hawks, Jeff A; Kunowski, Jacob; Platt, Stephen R

    2012-10-01

    Laparoscopy is beneficial to patients as measured by less painful recovery and an earlier return to functional health compared to conventional open surgery. However, laparoscopy requires the manipulation of long, slender tools from outside the patient's body. As a result, laparoscopy generally benefits only patients undergoing relatively simple procedures. An innovative approach to laparoscopy uses miniature in vivo robots that fit entirely inside the abdominal cavity. Our previous work demonstrated that a mobile, wireless robot platform can be successfully operated inside the abdominal cavity with different payloads (biopsy, camera, and physiological sensors). We hope that these robots are a step toward reducing the invasiveness of laparoscopy. The current study presents design details and results of laboratory and in vivo demonstrations of several new payload designs (clamping, cautery, and liquid delivery). Laboratory and in vivo cooperation demonstrations between multiple robots are also presented.

  6. High Q, Miniaturized LCP-Based Passive Components

    KAUST Repository

    Shamim, Atif

    2014-10-16

    Various methods and systems are provided for high Q, miniaturized LCP-based passive components. In one embodiment, among others, a spiral inductor includes a center connection and a plurality of inductors formed on a liquid crystal polymer (LCP) layer, the plurality of inductors concentrically spiraling out from the center connection. In another embodiment, a vertically intertwined inductor includes first and second inductors including a first section disposed on a side of the LCP layer forming a fraction of a turn and a second section disposed on another side of the LCP layer. At least a portion of the first section of the first inductor is substantially aligned with at least a portion of the second section of the second inductor and at least a portion of the first section of the second inductor is substantially aligned with at least a portion of the second section of the first inductor.

  7. Miniaturized High-Speed Modulated X-Ray Source

    Science.gov (United States)

    Gendreau, Keith C. (Inventor); Arzoumanian, Zaven (Inventor); Kenyon, Steven J. (Inventor); Spartana, Nick Salvatore (Inventor)

    2015-01-01

    A miniaturized high-speed modulated X-ray source (MXS) device and a method for rapidly and arbitrarily varying with time the output X-ray photon intensities and energies. The MXS device includes an ultraviolet emitter that emits ultraviolet light, a photocathode operably coupled to the ultraviolet light-emitting diode that emits electrons, an electron multiplier operably coupled to the photocathode that multiplies incident electrons, and an anode operably coupled to the electron multiplier that is configured to produce X-rays. The method for modulating MXS includes modulating an intensity of an ultraviolet emitter to emit ultraviolet light, generating electrons in response to the ultraviolet light, multiplying the electrons to become more electrons, and producing X-rays by an anode that includes a target material configured to produce X-rays in response to impact of the more electrons.

  8. A Miniature Data Repository on a Raspberry Pi

    Directory of Open Access Journals (Sweden)

    Argyrios Samourkasidis

    2016-12-01

    Full Text Available 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. We designed and implemented a software tool called Airchive to run on a Raspberry Pi, in order to assemble a data repository for archiving and openly sharing timeseries data. Airchive employs a relational database for storing data and implements two standards for sharing data (namely the Sensor Observation Service by the Open Geospatial Consortium and the Protocol for Metadata Harvesting by the Open Archives Initiative. The system is demonstrated in a realistic indoor air pollution data acquisition scenario in a four-month experiment evaluating its autonomy and robustness under power and network disruptions. A stress test was also conducted to evaluate its performance against concurrent client requests.

  9. Miniaturized day/night sight in Soldato Futuro program

    Science.gov (United States)

    Landini, Alberto; Cocchi, Alessandro; Bardazzi, Riccardo; Sardelli, Mauro; Puntri, Stefano

    2013-06-01

    The market of the sights for the 5.56 mm assault rifles is dominated by mainly three types of systems: TWS (Thermal Weapon Sight), the Pocket Scope with Weapon Mount and the Clip-on. The latter are designed primarily for special forces and snipers use, while the TWS design is triggered mainly by the DRI (Detection, Recognition, Identification) requirements. The Pocket Scope design is focused on respecting the SWaP (Size, Weight and Power dissipation) requirements. Compared to the TWS systems, for the last two years there was a significant technological growth of the Pocket Scope/Weapon Mount solutions, concentrated on the compression of the overall dimensions. The trend for the assault rifles is the use of small size/light weight (SWaP) IR sights, suitable mainly for close combat operations but also for extraordinary use as pocket scopes - handheld or helmet mounted. The latest developments made by Selex ES S.p.A. are responding precisely to the above-mentioned trend, through a miniaturized Day/Night sight embedding state-of-the art sensors and using standard protocols (USB 2.0, Bluetooth 4.0) for interfacing with PDAs, Wearable computers, etc., while maintaining the "shoot around the corner" capability. Indeed, inside the miniaturized Day/Night sight architecture, a wireless link using Bluetooth technology has been implemented to transmit the video streaming of the rifle sight to an helmet mounted display. The video of the rifle sight is transmitted only to the eye-piece of the soldier shouldering the rifle.

  10. Miniaturized Environmental Scanning Electron Microscope for In Situ Planetary Studies

    Science.gov (United States)

    Gaskin, Jessica; Abbott, Terry; Medley, Stephanie; Gregory, Don; Thaisen, Kevin; Taylor , Lawrence; Ramsey, Brian; Jerman, Gregory; Sampson, Allen; Harvey, Ralph

    2010-01-01

    The exploration of remote planetary surfaces calls for the advancement of low power, highly-miniaturized instrumentation. Instruments of this nature that are capable of multiple types of analyses will prove to be particularly useful as we prepare for human return to the moon, and as we continue to explore increasingly remote locations in our Solar System. To this end, our group has been developing a miniaturized Environmental-Scanning Electron Microscope (mESEM) capable of remote investigations of mineralogical samples through in-situ topographical and chemical analysis on a fine scale. The functioning of an SEM is well known: an electron beam is focused to nanometer-scale onto a given sample where resulting emissions such as backscattered and secondary electrons, X-rays, and visible light are registered. Raster scanning the primary electron beam across the sample then gives a fine-scale image of the surface topography (texture), crystalline structure and orientation, with accompanying elemental composition. The flexibility in the types of measurements the mESEM is capable of, makes it ideally suited for a variety of applications. The mESEM is appropriate for use on multiple planetary surfaces, and for a variety of mission goals (from science to non-destructive analysis to ISRU). We will identify potential applications and range of potential uses related to planetary exploration. Over the past few of years we have initiated fabrication and testing of a proof-of-concept assembly, consisting of a cold-field-emission electron gun and custom high-voltage power supply, electrostatic electron-beam focusing column, and scanning-imaging electronics plus backscatter detector. Current project status will be discussed. This effort is funded through the NASA Research Opportunities in Space and Earth Sciences - Planetary Instrument Definition and Development Program.

  11. Real-Time Food Authentication Using a Miniature Mass Spectrometer.

    Science.gov (United States)

    Gerbig, Stefanie; Neese, Stephan; Penner, Alexander; Spengler, Bernhard; Schulz, Sabine

    2017-10-17

    Food adulteration is a threat to public health and the economy. In order to determine food adulteration efficiently, rapid and easy-to-use on-site analytical methods are needed. In this study, a miniaturized mass spectrometer in combination with three ambient ionization methods was used for food authentication. The chemical fingerprints of three milk types, five fish species, and two coffee types were measured using electrospray ionization, desorption electrospray ionization, and low temperature plasma ionization. Minimum sample preparation was needed for the analysis of liquid and solid food samples. Mass spectrometric data was processed using the laboratory-built software MS food classifier, which allows for the definition of specific food profiles from reference data sets using multivariate statistical methods and the subsequent classification of unknown data. Applicability of the obtained mass spectrometric fingerprints for food authentication was evaluated using different data processing methods, leave-10%-out cross-validation, and real-time classification of new data. Classification accuracy of 100% was achieved for the differentiation of milk types and fish species, and a classification accuracy of 96.4% was achieved for coffee types in cross-validation experiments. Measurement of two milk mixtures yielded correct classification of >94%. For real-time classification, the accuracies were comparable. Functionality of the software program and its performance is described. Processing time for a reference data set and a newly acquired spectrum was found to be 12 s and 2 s, respectively. These proof-of-principle experiments show that the combination of a miniaturized mass spectrometer, ambient ionization, and statistical analysis is suitable for on-site real-time food authentication.

  12. The Use of a Sheathless Basket via Miniature Ureteroscopes.

    Science.gov (United States)

    Watson, G

    1995-01-01

    The conventional use of a basket involves a metallic wire section that is contained within a polythene sheath. The wire basket can be withdrawn or protruded from the sheath using a handle. The advantage of this system is that the basket can be kept shut or open at will within the ureter. Thus one can keep the basket closed in order to maneuver the basket past a stone before opening it above the stone. With the development of efficient and safe lithotripsy modalities becoming widely available and with miniaturization of these and the ureteroscopes, it is becoming less common to dilate the ureter. Therefore it is not frequently possible to extract a stone intact. Baskets still can be used secondarily to extract the fragments. It is possible to use the basket wire without its sheath. The ureteroscope channel effectively becomes the sheath, and the basket opens immediately on protruding it beyond the ureteroscope. This has the following advantages: (a) A larger-diameter basket wire can be introduced. The very small baskets of 2F and 3F used via miniature ureteroscopes are very flimsy. When the sheath is removed, it becomes possible to use an otherwise 3F basket via a 2F channel. (b)The operator can work the basket usingjust two fingers close to the instrument channel port. This is more ergonomic than working an opening mechanism at the end of the basket, because this latter system takes the operator's hand away from the instrument. (c) The basket can be detached more readily from the ureteroscope, should it become, impacted together with a stone within the ureter. This makes it possible to reinsert the ureteroscope alongside the basket and fragment the stone within the basket, provided that there is no reinforced section to the inner wire at the handle.

  13. Miniaturization of speckle interferometry for rapid strain analysis

    Science.gov (United States)

    Wegner, Ronny; Ettemeyer, Andreas

    1999-09-01

    Today's industry demands high-performance components meeting toughest mechanical features and ultimate safety standards. Especially in automotive and aircraft industry the development focuses on tailor-made design and solutions according to customer specifications. To reconcile economy, light-weight construction has become a key issue. Many companies are looking for new advanced strain/stress analysis techniques to improve cost efficiency and the limitations of classical methods. Detection of weak points and fatigue tests are carried out mainly with strain gauges which need careful application and experience. ESPI (electronic speckle pattern interferometry) allows a rapid, full field and 3D-measurement without contact. This paper presents the principle and application of a new miniaturized laser optical sensor combining contour and deformation measurement. In its basic employment ESPI is an interferometric method measuring deformations at modern working materials with high accuracy. Here also a module for contouring was developed and integrated into a single interferometer. Therefore even at complex components it is possible to measure and display strain-fields and -gradients with respect to the underlying contour. The new sensor is a unique device for flexible strain-analysis at welded-materials, extrusions, engines, car-bodies, etc. Without preparation and due to the full field and 3D- measurement 'hot spots' are shown, reducing the testing procedure and increasing the reliability of the complex component testing significantly. In this paper the recent development of a miniaturized ESPI-interferometer for strain and stress measurement is described. Advanced features according to classical techniques are specified and new applications in material and component testing are presented.

  14. Transapical miniaturized ventricular assist device: Design and initial testing

    Science.gov (United States)

    Slaughter, Mark S.; Giridharan, Guruprasad A.; Tamez, Dan; LaRose, Jeff; Sobieski, Mike A.; Sherwood, Leslie; Koenig, Steven C.

    2013-01-01

    Background Left ventricular assist devices are increasingly used to treat patients with advanced and otherwise refractory heart failure as bridge to transplant or destination therapy. We evaluated a new miniaturized left ventricular assist device that requires minimal surgery for implantation, potentially allowing implantation in earlier stage heart failure. Methods HeartWare (Miami Lakes, Fla) developed transapical miniaturized ventricular assist device. Acute (n = 4), 1-week (n = 2), and 30-day (n = 4) bovine model experiments evaluated hemodynamic efficacy and biocompatibility of the device, which was implanted through small left thoracotomy with single insertion at apex of left ventricle without cardiopulmonary bypass. The device outflow cannula was positioned across the aortic valve. The international normalized ratio was maintained between 2.0 and 2.5 with warfarin. Hemodynamic, echocardiographic, fluoroscopic, hematologic, and blood chemistry measurements were evaluated. Results The device was successfully implanted through the left ventricular apex in all 10 animals. The device was operated at 15,000 ± 1000 rpm (power consumption, 3.5–6.0 W). The device maintained normal end-organ perfusion with no significant hemolysis (0–30 mg/dL). There were no pump failures or device-related complications. At autopsy, no abnormalities were seen in endocardium, aortic valve leaflets, or aortic root. There was no evidence of thromboembolism or abnormalities in any peripheral end organs. Conclusions We successfully demonstrated feasibility of a novel intraventricular assist device that can be completely implanted through left ventricular apex. This transapical surgical approach eliminates needs for sternotomy, device pocket, cardiopulmonary bypass, ventricular coring, and construction of an outflow graft anastomosis. PMID:21320708

  15. Spontaneous Metacognition in Rhesus Monkeys.

    Science.gov (United States)

    Rosati, Alexandra G; Santos, Laurie R

    2016-09-01

    Metacognition is the ability to think about thinking. Although monitoring and controlling one's knowledge is a key feature of human cognition, its evolutionary origins are debated. In the current study, we examined whether rhesus monkeys (Macaca mulatta; N = 120) could make metacognitive inferences in a one-shot decision. Each monkey experienced one of four conditions, observing a human appearing to hide a food reward in an apparatus consisting of either one or two tubes. The monkeys tended to search the correct location when they observed this baiting event, but engaged in information seeking-by peering into a center location where they could check both potential hiding spots-if their view had been occluded and information seeking was possible. The monkeys only occasionally approached the center when information seeking was not possible. These results show that monkeys spontaneously use information about their own knowledge states to solve naturalistic foraging problems, and thus provide the first evidence that nonhumans exhibit information-seeking responses in situations with which they have no prior experience. © The Author(s) 2016.

  16. Spontaneous flocking in human groups.

    Science.gov (United States)

    Belz, Michael; Pyritz, Lennart W; Boos, Margarete

    2013-01-01

    Flocking behaviour, as a type of self-organised collective behaviour, is described as the spatial formation of groups without global control and explicit inter-individual recruitment signals. It can be observed in many animals, such as bird flocks, shoals or herds of ungulates. Spatial attraction between humans as the central component of flocking behaviour has been simulated in a number of seminal models but it has not been detected experimentally in human groups so far. The two other sub-processes of this self-organised collective movement - collision avoidance and alignment - are excluded or held constant respectively in this study. We created a computer-based, multi-agent game where human players, represented as black dots, moved on a virtual playground. The participants were deprived of social cues about each other and could neither communicate verbally nor nonverbally. They played two games: (1) Single Game, where other players were invisible, and (2) Joint Game, where each player could see players' positions in a local radius around himself/herself. We found that individuals approached their neighbours spontaneously if their positions were visible, leading to less spatial dispersion of the whole group compared to moving alone. We conclude that human groups show the basic component of flocking behaviour without being explicitly instructed or rewarded to do so. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Simultaneous bilateral primary spontaneous pneumothorax

    Directory of Open Access Journals (Sweden)

    Arife Zeybek

    2014-04-01

    Full Text Available Simultaneous bilateral primary pneumothorax is a very rare (1.6 / 100,000 and life-threatening condition. Clinical presentation may vary from mild dyspnea to tension pneumothorax. It may be milder particularly in younger patients, but more severe in patients with advanced age, and tube thoracostomy is a life preserver in the latter group. Since mortality and recurrence rates following tube thoracostomy are high, endoscopic approaches to bilateral hemithorax have been reported in literature. Apical wedge resection and pleural procedures are recommended in video thoracoscopy or mini thoracotomy even if no bulla and/or bleb are detected. Bilateral surgical interventions and additional pleural procedures are associated with increased rate of post-operative complications and longer postoperative hospital-stays. As a first-line approach, the surgical method toward any side of lung with air leakage following a previous tube thoracostomy is considered less invasive, especially in younger patients. Here, we present a case of simultaneous bilateral primary spontaneous pneumothorax (SBPSP in a 21-year old male with no history of smoking and chronic pulmonary disease. A unilateral surgical intervention was performed, and no recurrence was observed during 5-year follow up.

  18. Bilateral spontaneous hemotympanum: Case report

    Directory of Open Access Journals (Sweden)

    Economou Nicolas C

    2006-10-01

    Full Text Available Abstract Background The most common causes of hemotympanum are therapeutic nasal packing, epistaxis, blood disorders and blunt trauma to the head. Hemotympanum is characterized as idiopathic, when it is detected in the presence of chronic otitis media. A rare case of spontaneous bilateral hemotympanum in a patient treated with anticoagulants is presented herein. Case presentation A 72-year-old male presented with acute deterioration of hearing. In the patient's medical history aortic valve replacement 1 year before presentation was reported. Since then he had been administered regularly coumarinic anticoagulants, with INR levels maintained between 3.4 and 4.0. Otoscopy revealed the presence of bilateral hemotympanum. The audiogram showed symmetrical moderately severe mixed hearing loss bilaterally, with the conductive component predominating. Tympanograms were flat bilaterally with absent acoustic reflexes. A computerized tomography scan showed the presence of fluid in the mastoid and middle ear bilaterally. Treatment was conservative and consisted of a 10-day course of antibiotics, anticongestants and temporary interruption of the anticoagulant therapy. After 3 weeks, normal tympanic membranes were found and hearing had returned to previous levels. Conclusion Anticoagulant intake should be included in the differential diagnosis of hemotympanum, because its detection and appropriate treatment may lead to resolution of the disorder.

  19. Serum triglyceride concentrations in Miniature Schnauzers with and without a history of probable pancreatitis.

    Science.gov (United States)

    Xenoulis, P G; Levinski, M D; Suchodolski, J S; Steiner, J M

    2011-01-01

    The association between hypertriglyceridemia and pancreatitis remains obscure in dogs. A possible role of hypertriglyceridemia as a cause of pancreatitis in Miniature Schnauzers has been suspected. To compare serum triglyceride concentrations between Miniature Schnauzers with and without a recent history of pancreatitis. Seventeen Miniature Schnauzers with a history of pancreatitis (group 1) and 34 age-matched Miniature Schnauzers without a history of pancreatitis (group 2) were prospectively enrolled. Prospective case-control study. Two samples were collected from each of the 17 Miniature Schnauzers with pancreatitis: 1 during pancreatitis and 1 after clinical and biochemical resolution of pancreatitis. Serum triglyceride and cholesterol concentrations were compared between group 1 (after resolution of pancreatitis) and group 2. Miniature Schnauzers in group 1 were significantly more likely to have hypertriglyceridemia (>108 mg/dL) (71%) after resolution of pancreatitis than Miniature Schnauzers in group 2 (33%; odds ratio = 5.02; 95% confidence interval = 1.4-17.8; P = .0163). Serum triglyceride concentrations were significantly higher in dogs of group 1 (median: 605.0 mg/dL) after resolution of pancreatitis than in dogs of group 2 (median: 73.5 mg/dL; P = .002). Miniature Schnauzers with a history of pancreatitis were 5 times more likely to have hypertriglyceridemia than controls. Hypertriglyceridemia might be associated with the development of pancreatitis in some dogs of this breed. Additional studies are needed to further clarify the role of hypertriglyceridemia in the development of pancreatitis in Miniature Schnauzers as well as other dog breeds. Copyright © 2010 by the American College of Veterinary Internal Medicine.

  20. Isogenic FUS-eGFP iPSC Reporter Lines Enable Quantification of FUS Stress Granule Pathology that Is Rescued by Drugs Inducing Autophagy

    Directory of Open Access Journals (Sweden)

    Lara Marrone

    2018-02-01

    Full Text Available Summary: Perturbations in stress granule (SG dynamics may be at the core of amyotrophic lateral sclerosis (ALS. Since SGs are membraneless compartments, modeling their dynamics in human motor neurons has been challenging, thus hindering the identification of effective therapeutics. Here, we report the generation of isogenic induced pluripotent stem cells carrying wild-type and P525L FUS-eGFP. We demonstrate that FUS-eGFP is recruited into SGs and that P525L profoundly alters their dynamics. With a screening campaign, we demonstrate that PI3K/AKT/mTOR pathway inhibition increases autophagy and ameliorates SG phenotypes linked to P525L FUS by reducing FUS-eGFP recruitment into SGs. Using a Drosophila model of FUS-ALS, we corroborate that induction of autophagy significantly increases survival. Finally, by screening clinically approved drugs for their ability to ameliorate FUS SG phenotypes, we identify a number of brain-penetrant anti-depressants and anti-psychotics that also induce autophagy. These drugs could be repurposed as potential ALS treatments. : Sterneckert and colleagues generate isogenic FUS-eGFP reporter iPSCs that enable the identification of stress granule (SG phenotypes specifically induced by the ALS mutation FUS P525L. Compound screening shows that modulation of the PI3K/AKT/mTOR pathway regulating autophagy ameliorates SG phenotypes. A second screen identifies similarly acting brain-penetrant US FDA-approved drugs that could be repurposed to treat ALS. Keywords: amyotrophic lateral sclerosis, induced pluripotent stem cells, FUS, stress granules, autophagy, gene editing, CRISPR/Cas9n

  1. 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.

  2. Clock frequency estimation under spontaneous emission

    Science.gov (United States)

    Qin, Xi-Zhou; Huang, Jia-Hao; Zhong, Hong-Hua; Lee, Chaohong

    2018-02-01

    We investigate the quantum dynamics of a driven two-level system under spontaneous emission and its application in clock frequency estimation. By using the Lindblad equation to describe the system, we analytically obtain its exact solutions, which show three different regimes: Rabi oscillation, damped oscillation, and overdamped decay. From the analytical solutions, we explore how the spontaneous emission affects the clock frequency estimation. We find that under a moderate spontaneous emission rate, the transition frequency can still be inferred from the Rabi oscillation. Our results enable potential practical applications in frequency measurement and quantum control under decoherence.

  3. 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.

  4. Spontaneous regression of an invasive thymoma.

    Science.gov (United States)

    Yutaka, Yojiro; Omasa, Mitsugu; Shikuma, Kei; Okuda, Masato; Taki, Toshihiko

    2009-05-01

    Although there are many reports of spontaneous regression of noninvasive thymoma, there are no reports of spontaneous regression of an invasive thymoma. Moreover, the mechanism of the spontaneous regression is still unknown. The present case concerns a 47-year-old man who presented with chest pain. Computed tomography (CT) showed a large anterior mediastinal mass with left pleural effusion that occluded the innominate vein. The tissue obtained by video-assisted thoracic surgery suggested a diagnosis of invasive thymic carcinoma. One month later CT showed prominent regression of the tumor, and the tumor was completely resected. On pathology, the diagnosis was thymoma type B3.

  5. Spontaneous Dissection of the Superior Mesenteric Artery

    International Nuclear Information System (INIS)

    Sheldon, Patrick J.; Esther, James B.; Sheldon, Elana L.; Sparks, Steven R.; Brophy, David P.; Oglevie, Steven B.

    2001-01-01

    Spontaneous dissection of the superior mesenteric artery (SMA) is a rare occurrence, especially when not associated with aortic dissection. Currently, only 28 cases appear to have been reported. Due to the scarcity of cases in the literature, the natural history of isolated, spontaneous SMA dissection is unclear. CT has been reported to be useful for the initial diagnosis of SMA dissection [2-5]. We present two recent cases of spontaneous SMA dissection in which enhanced spiral CT was instrumental in following the disease process and guiding clinical decision making

  6. 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.

  7. 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 ...

  8. Right Diaphragm Spontaneous Rupture: A Surgical Approach

    Directory of Open Access Journals (Sweden)

    Duilio Divisi

    2011-01-01

    Full Text Available We present a case of spontaneous rupture of the diaphragm, characterized by nonspecific symptoms. The rapid diagnosis and appropriate surgical approach led to a positive resolution of the pathology.

  9. Spontaneous cecal perforation secondary to acute fulminant ...

    African Journals Online (AJOL)

    Spontaneous cecal perforation secondary to acute fulminant gastroenteritis: report of a rare case. Duvuru Ram, Vilvapathy S. Karthikeyan, Sarath C. Sistla, Sheik M. Ali, Parnandi Sridhar, Nagarajan Rajkumar ...

  10. Spontaneous Trait Inferences on Social Media.

    Science.gov (United States)

    Levordashka, Ana; Utz, Sonja

    2017-01-01

    The present research investigates whether spontaneous trait inferences occur under conditions characteristic of social media and networking sites: nonextreme, ostensibly self-generated content, simultaneous presentation of multiple cues, and self-paced browsing. We used an established measure of trait inferences (false recognition paradigm) and a direct assessment of impressions. Without being asked to do so, participants spontaneously formed impressions of people whose status updates they saw. Our results suggest that trait inferences occurred from nonextreme self-generated content, which is commonly found in social media updates (Experiment 1) and when nine status updates from different people were presented in parallel (Experiment 2). Although inferences did occur during free browsing, the results suggest that participants did not necessarily associate the traits with the corresponding status update authors (Experiment 3). Overall, the findings suggest that spontaneous trait inferences occur on social media. We discuss implications for online communication and research on spontaneous trait inferences.

  11. Spontane abdominale arteriovenøse fistler

    DEFF Research Database (Denmark)

    Flarup, S; Lindholt, Jes Sanddal

    1997-01-01

    Spontaneous arteriovenous fistulas between major abdominal vessels (AAVF) complicates about 1% of abdominal aortic aneurysms. AAVF produces severe circulatory disturbances with high operative mortality. Preoperative diagnosis is important but difficult due to the varied nature of presentation. Fo...

  12. Depressive disorder and grief following spontaneous abortion.

    Science.gov (United States)

    Kulathilaka, Susil; Hanwella, Raveen; de Silva, Varuni A

    2016-04-12

    Abortion is associated with moderate to high risk of psychological problems such as depression, use of alcohol or marijuana, anxiety, depression and suicidal behaviours. The increased risk of depression after spontaneous abortion in Asian populations has not been clearly established. Only a few studies have explored the relationship between grief and depression after abortion. A study was conducted to assess the prevalence and risk factors of depressive disorder and complicated grief among women 6-10 weeks after spontaneous abortion and compare the risk of depression with pregnant women attending an antenatal clinic. Spontaneous abortion group consisted of women diagnosed with spontaneous abortion by a Consultant Obstetrician. Women with confirmed or suspected induced abortion were excluded. The comparison group consisted of randomly selected pregnant, females attending the antenatal clinics of the two hospitals. Diagnosis of depressive disorder was made according to ICD-10 clinical criteria based on a structured clinical interview. This assessment was conducted in both groups. The severity of depressive symptoms were assessed using the Patients Health Questionnaire (PHQ-9). Grief was assessed using the Perinatal Grief Scale which was administered to the women who had experienced spontaneous abortion. The sample consisted of 137 women in each group. The spontaneous abortion group (mean age 30.39 years (SD = 6.38) were significantly older than the comparison group (mean age 28.79 years (SD = 6.26)). There were more females with ≥10 years of education in the spontaneous abortion group (n = 54; SD = 39.4) compared to the comparison group (n = 37; SD = 27.0). The prevalence of depression in the spontaneous abortion group was 18.6 % (95 CI, 11.51-25.77). The prevalence of depression in the comparison group was 9.5 % (95 CI, 4.52-14.46). Of the 64 women fulfilling criteria for grief, 17 (26.6 %) also fulfilled criteria for a depressive episode. The relative risk of

  13. 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.

  14. Postmenopausal spontaneous uterine perforation: Case report

    Science.gov (United States)

    İşlek Seçen, Elçin; Ağış, Hilal; Altunkaya, Canan; Avşar, Ayşe Filiz

    2015-01-01

    Spontaneous uterine rupture and generalized peritonitis caused by pyometra occurs rarely with high morbidity and mortality. A correct and definite diagnosis can be made with laparotomy or laparoscopy. The clinical findings of perforated pyometra are similar to perforation of the gastrointestinal tract and gynecologic symptoms are less frequent, which makes preoperative diagnosis difficult. We report a case of a patient aged 82 years who underwent surgery for spontaneous uterine rupture and generalized peritonitis as a result of pyometra. PMID:28913055

  15. Endometriosis-related spontaneous diaphragmatic rupture.

    Science.gov (United States)

    Triponez, Frédéric; Alifano, Marco; Bobbio, Antonio; Regnard, Jean-François

    2010-10-01

    Non-traumatic, spontaneous diaphragmatic rupture is a rare event whose pathophysiology is not known. We report the case of endometriosis-related spontaneous rupture of the right diaphragm with intrathoracic herniation of the liver, gallbladder and colon. We hypothesize that the invasiveness of endometriotic tissue caused diaphragm fragility, which finally lead to its complete rupture without traumatic event. The treatment consisted of a classical management of diaphragmatic rupture, with excision of the endometriotic nodule followed by medical ovarian suppression for six months.

  16. Spontaneous regression of metastatic Merkel cell carcinoma.

    LENUS (Irish Health Repository)

    Hassan, S J

    2010-01-01

    Merkel cell carcinoma is a rare aggressive neuroendocrine carcinoma of the skin predominantly affecting elderly Caucasians. It has a high rate of local recurrence and regional lymph node metastases. It is associated with a poor prognosis. Complete spontaneous regression of Merkel cell carcinoma has been reported but is a poorly understood phenomenon. Here we present a case of complete spontaneous regression of metastatic Merkel cell carcinoma demonstrating a markedly different pattern of events from those previously published.

  17. Spontaneous intracranial epidural hematoma during rivaroxaban treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ruschel, Leonardo Gilmone; Rego, Felipe Marques Monteiro do; Milano, Jeronimo Buzetti; Jung, Gustavo Simiano; Silva Junior, Luis Fernando; Ramina, Ricardo, E-mail: leonardoruschel@yahoo.com.br [Instituto de Neurologia de Curitiba (INC), Curitiba, PR (Brazil)

    2016-11-15

    According to our research, this is the first case described in the literature of spontaneous intracranial epidural hematoma secondary to the use of Xarelto®. Spontaneous intracranial epidural hematomas are rarely described in the literature. They are associated with infectious diseases of the skull, coagulation disorders, vascular malformations of the dura mater and metastasis to the skull. Long-term post-marketing monitoring and independent reports will probably detect the full spectrum of hemorrhagic complications of the use of rivaroxaban. (author)

  18. Spontaneous intracranial epidural hematoma during rivaroxaban treatment.

    Science.gov (United States)

    Ruschel, Leonardo Gilmone; Rego, Felipe Marques Monteiro do; Milano, Jerônimo Buzetti; Jung, Gustavo Simiano; Silva, Luis Fernando; Ramina, Ricardo

    2016-11-01

    According to our research, this is the first case described in the literature of spontaneous intracranial epidural hematoma secondary to the use of Xareltor. Spontaneous intracranial epidural hematomas are rarely described in the literature. They are associated with infectious diseases of the skull, coagulation disorders, vascular malformations of the dura mater and metastasis to the skull. Long-term post-marketing monitoring and independent reports will probably detect the full spectrum of hemorrhagic complications of the use of rivaroxaban.

  19. 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.

  20. CRUQS: A Miniature Fine Sun Sensor for Nanosatellites

    Science.gov (United States)

    Heatwole, Scott; Snow, Carl; Santos, Luis

    2013-01-01

    A new miniature fine Sun sensor has been developed that uses a quadrant photodiode and housing to determine the Sun vector. Its size, mass, and power make it especially suited to small satellite applications, especially nanosatellites. Its accuracy is on the order of one arcminute, and it will enable new science in the area of nanosatellites. The motivation for this innovation was the need for high-performance Sun sensors in the nanosatellite category. The design idea comes out of the LISS (Lockheed Intermediate Sun Sensor) used by the sounding rocket program on their solar pointing ACS (Attitude Control System). This system uses photodiodes and a wall between them. The shadow cast by the Sun is used to determine the Sun angle. The new sensor takes this concept and miniaturizes it. A cruciform shaped housing and a surface-mount quadrant photodiode package allow for a two-axis fine Sun sensor to be packaged into a space approx.1.25xl x0.25 in. (approx.3.2x2.5x0.6 cm). The circuitry to read the photodiodes is a simple trans-impedance operational amplifier. This is much less complex than current small Sun sensors for nanosatellites that rely on photo-arrays and processing of images to determine the Sun center. The simplicity of the circuit allows for a low power draw as well. The sensor consists of housing with a cruciform machined in it. The cruciform walls are 0.5-mm thick and the center of the cruciform is situated over the center of the quadrant photodiode sensor. This allows for shadows to be cast on each of the four photodiodes based on the angle of the Sun. A simple operational amplifier circuit is used to read the output of the photodiodes as a voltage. The voltage output of each photodiode is summed based on rows and columns, and then the values of both rows or both columns are differenced and divided by the sum of the voltages for all four photodiodes. The value of both difference over sums for the rows and columns is compared to a table or a polynomial fit