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Sample records for mice demonstrate features

  1. The MICE Demonstration of Ionization Cooling

    SciTech Connect

    Pasternak, J.; Blackmore, V.; Hunt, C.; Lagrange, J-B.; Long, K.; Collomb, N.; Snopok, P.

    2015-05-01

    Muon beams of low emittance provide the basis for the intense, well-characterised neutrino beams necessary to elucidate the physics of flavour at the Neutrino Factory and to provide lepton-antilepton collisions at energies of up to several TeV at the Muon Collider. The International Muon Ionization Cooling Experiment (MICE) will demonstrate ionization cooling, the technique by which it is proposed to reduce the phase-space volume occupied by the muon beam at such facilities. In an ionization cooling channel, the muon beam passes through a material (the absorber) in which it loses energy. The energy lost is then replaced using RF cavities. The combined effect of energy loss and re-acceleration is to reduce the transverse emittance of the beam (transverse cooling). A major revision of the scope of the project was carried out over the summer of 2014. The revised project plan, which has received the formal endorsement of the international MICE Project Board and the international MICE Funding Agency Committee, will deliver a demonstration of ionization cooling by September 2017. In the revised configuration a central lithium-hydride absorber provides the cooling effect. The magnetic lattice is provided by the two superconducting focus coils and acceleration is provided by two 201 MHz single-cavity modules. The phase space of the muons entering and leaving the cooling cell will be measured by two solenoidal spectrometers. All the superconducting magnets for the ionization cooling demonstration are available at the Rutherford Appleton Laboratory and the first single-cavity prototype is under test in the MuCool Test Area at Fermilab. The design of the cooling demonstration experiment will be described together with a summary of the performance of each of its components. The cooling performance of the revised configuration will also be presented.

  2. Interleukin-11 alters placentation and causes preeclampsia features in mice

    PubMed Central

    Winship, Amy L.; Koga, Kaori; Menkhorst, Ellen; Van Sinderen, Michelle; Rainczuk, Katarzyna; Nagai, Miwako; Cuman, Carly; Yap, Joanne; Zhang, Jian-Guo; Simmons, David; Young, Morag J.; Dimitriadis, Evdokia

    2015-01-01

    Preeclampsia (PE) is a pregnancy-specific disorder characterized by hypertension and proteinuria after 20 wk gestation. Abnormal extravillous trophoblast (EVT) invasion and remodeling of uterine spiral arterioles is thought to contribute to PE development. Interleukin-11 (IL11) impedes human EVT invasion in vitro and is elevated in PE decidua in women. We demonstrate that IL11 administered to mice causes development of PE features. Immunohistochemistry shows IL11 compromises trophoblast invasion, spiral artery remodeling, and placentation, leading to increased systolic blood pressure (SBP), proteinuria, and intrauterine growth restriction, although nonpregnant mice were unaffected. Real-time PCR array analysis identified pregnancy-associated plasma protein A2 (PAPPA2), associated with PE in women, as an IL11 regulated target. IL11 increased PAPPA2 serum and placental tissue levels in mice. In vitro, IL11 compromised primary human EVT invasion, whereas siRNA knockdown of PAPPA2 alleviated the effect. Genes regulating uterine natural killer (uNK) recruitment and differentiation were down-regulated and uNK cells were reduced after IL11 treatment in mice. IL11 withdrawal in mice at onset of PE features reduced SBP and proteinuria to control levels and alleviated placental labyrinth defects. In women, placental IL11 immunostaining levels increased in PE pregnancies and in serum collected from women before development of early-onset PE, shown by ELISA. These results indicate that elevated IL11 levels result in physiological changes at the maternal–fetal interface, contribute to abnormal placentation, and lead to the development of PE. Targeting placental IL11 may provide a new treatment option for PE. PMID:26655736

  3. Interleukin-11 alters placentation and causes preeclampsia features in mice.

    PubMed

    Winship, Amy L; Koga, Kaori; Menkhorst, Ellen; Van Sinderen, Michelle; Rainczuk, Katarzyna; Nagai, Miwako; Cuman, Carly; Yap, Joanne; Zhang, Jian-Guo; Simmons, David; Young, Morag J; Dimitriadis, Evdokia

    2015-12-29

    Preeclampsia (PE) is a pregnancy-specific disorder characterized by hypertension and proteinuria after 20 wk gestation. Abnormal extravillous trophoblast (EVT) invasion and remodeling of uterine spiral arterioles is thought to contribute to PE development. Interleukin-11 (IL11) impedes human EVT invasion in vitro and is elevated in PE decidua in women. We demonstrate that IL11 administered to mice causes development of PE features. Immunohistochemistry shows IL11 compromises trophoblast invasion, spiral artery remodeling, and placentation, leading to increased systolic blood pressure (SBP), proteinuria, and intrauterine growth restriction, although nonpregnant mice were unaffected. Real-time PCR array analysis identified pregnancy-associated plasma protein A2 (PAPPA2), associated with PE in women, as an IL11 regulated target. IL11 increased PAPPA2 serum and placental tissue levels in mice. In vitro, IL11 compromised primary human EVT invasion, whereas siRNA knockdown of PAPPA2 alleviated the effect. Genes regulating uterine natural killer (uNK) recruitment and differentiation were down-regulated and uNK cells were reduced after IL11 treatment in mice. IL11 withdrawal in mice at onset of PE features reduced SBP and proteinuria to control levels and alleviated placental labyrinth defects. In women, placental IL11 immunostaining levels increased in PE pregnancies and in serum collected from women before development of early-onset PE, shown by ELISA. These results indicate that elevated IL11 levels result in physiological changes at the maternal-fetal interface, contribute to abnormal placentation, and lead to the development of PE. Targeting placental IL11 may provide a new treatment option for PE. PMID:26655736

  4. Software for Demonstration of Features of Chain Polymerization Processes

    ERIC Educational Resources Information Center

    Sosnowski, Stanislaw

    2013-01-01

    Free software for the demonstration of the features of homo- and copolymerization processes (free radical, controlled radical, and living) is described. The software is based on the Monte Carlo algorithms and offers insight into the kinetics, molecular weight distribution, and microstructure of the macromolecules formed in those processes. It also…

  5. Empirical demonstration of hybrid chromosomal races in house mice.

    PubMed

    Giménez, Mabel D; Panithanarak, Thadsin; Hauffe, Heidi C; Searle, Jeremy B

    2016-07-01

    Western house mice (Mus musculus domesticus) and common shrews (Sorex araneus) are important models for study of chromosomal speciation. Both had ancestral karyotypes consisting of telocentric chromosomes, and each is subdivided into numerous chromosomal races many of which have resulted from fixation of new mutations (Robertsonian fusions and whole-arm reciprocal translocations). However, some chromosomal races in both species may alternatively have originated through hybridization, with particular homozygous recombinant products reaching fixation. Here, we demonstrate the process of generation of hybrid chromosomal races for the first time in either species using molecular markers. Analysis of centromeric microsatellite markers show that the Mid Valtellina (IMVA) and Upper Valtellina (IUVA) chromosomal races of the house mouse are recombinant products of hybridization of the Lower Valtellina (ILVA) and Poschiavo (CHPO) chromosomal races, supporting earlier theoretical analysis. IMVA and IUVA occupy a small area of the Italian Alps where ILVA makes contact with CHPO. IUVA and CHPO have previously been shown to be reproductively isolated in one village, emphasizing that hybrid chromosomal races in small mammals, as in plants, have the potential to be part of the speciation process. PMID:27287407

  6. Intermittent cold stress enhances features of atherosclerotic plaque instability in apolipoprotein E‑deficient mice.

    PubMed

    Zheng, Xi; Wang, Qiang; Zhang, Yan; Yang, Dachun; Li, De; Tang, Bing; Li, Xiuchuan; Yang, Yongjian; Ma, Shuangtao

    2014-10-01

    The cold weather is associated with an increased occurrence of acute coronary events. However, the mechanisms underlying cold‑induced myocardial infarctions have not yet been fully elucidated. In the present study, 20 male, eight week‑old, apolipoprotein E (ApoE)‑deficient mice were subjected to either control conditions or intermittent cold exposure for eight weeks. Mice in the cold group were placed in a cold room at 4˚C for 4 h per day, while the mice in the control group were kept in a room at 24˚C. Cold‑exposed mice did not significantly differ from control mice in body weight, fasting glucose concentration and plasma lipid levels, including triglyceride, total cholesterol, low‑density lipoprotein and high‑density lipoprotein. The hematoxylin and eosin‑stained sections of the aortic root demonstrated increased plaque size in the cold group compared with the control group (P<0.01). Furthermore, cold‑treated mice exhibited significantly decreased plaque collagen and vascular smooth muscle cell deposition and increased macrophage and lymphocyte content (P<0.05 or P<0.01), which are typical features of atherosclerotic plaque instability. Additionally, the protein expression of matrix metalloproteinase (MMP)‑2, MMP‑9 and MMP‑14 were significantly increased (P<0.05 or P<0.01), whereas tissue inhibitor of matrix metalloproteinase (TIMP)‑1 expression was decreased (P<0.05) following exposure to a cold environment. The present study demonstrated that chronic intermittent cold stress may increase atherosclerotic plaque size and promote plaque instability in ApoE‑deficient mice by altering the balance of MMPs and TIMPs. These findings may provide mechanistic insights into sudden cardiac death in cold environments. PMID:25109747

  7. Prodynorphin knockout mice demonstrate diminished age-associated impairment in spatial water maze performance.

    PubMed

    Nguyen, Xuan V; Masse, James; Kumar, Ashok; Vijitruth, Rattanavijit; Kulik, Cynthia; Liu, Mei; Choi, Dong-Young; Foster, Thomas C; Usynin, Ivan; Bakalkin, Georgy; Bing, Guoying

    2005-06-20

    Dynorphins, endogenous kappa-opioid agonists widely expressed in the central nervous system, have been reported to increase following diverse pathophysiological processes, including excitotoxicity, chronic inflammation, and traumatic injury. These peptides have been implicated in cognitive impairment, especially that associated with aging. To determine whether absence of dynorphin confers any beneficial effect on spatial learning and memory, knockout mice lacking the coding exons of the gene encoding its precursor prodynorphin (Pdyn) were tested in a water maze task. Learning and memory assessment using a 3-day water maze protocol demonstrated that aged Pdyn knockout mice (13-17 months) perform comparatively better than similarly aged wild-type (WT) mice, based on acquisition and retention probe trial indices. There was no genotype effect on performance in the cued version of the swim task nor on average swim speed, suggesting the observed genotype effects are likely attributable to differences in cognitive rather than motor function. Young (3-6 months) mice performed significantly better than aged mice, but in young mice, no genotype difference was observed. To investigate the relationship between aging and brain dynorphin expression in mice, we examined dynorphin peptide levels at varying ages in hippocampus and frontal cortex of WT 129SvEv mice. Quantitative radioimmunoassay demonstrated that dynorphin A levels in frontal cortex, but not hippocampus, of 12- and 24-month mice were significantly elevated compared to 3-month mice. Although the underlying mechanisms have yet to be elucidated, the results suggest that chronic increases in endogenous dynorphin expression with age, especially in frontal cortex, may adversely affect learning and memory.

  8. Ames hypopituitary dwarf mice demonstrate imbalanced myelopoiesis between bone marrow and spleen.

    PubMed

    Capitano, Maegan L; Chitteti, Brahmananda R; Cooper, Scott; Srour, Edward F; Bartke, Andrzej; Broxmeyer, Hal E

    2015-06-01

    Ames hypopituitary dwarf mice are deficient in growth hormone, thyroid-stimulating hormone, and prolactin. The phenotype of these mice demonstrates irregularities in the immune system with skewing of the normal cytokine milieu towards a more anti-inflammatory environment. However, the hematopoietic stem and progenitor cell composition of the bone marrow (BM) and spleen in Ames dwarf mice has not been well characterized. We found that there was a significant decrease in overall cell count when comparing the BM and spleen of 4-5 month old dwarf mice to their littermate controls. Upon adjusting counts to differences in body weight between the dwarf and control mice, the number of granulocyte-macrophage progenitors, confirmed by immunophenotyping and colony-formation assay was increased in the BM. In contrast, the numbers of all myeloid progenitor populations in the spleen were greatly reduced, as confirmed by colony-formation assays. This suggests that there is a shift of myelopoiesis from the spleen to the BM of Ames dwarf mice; however, this shift does not appear to involve erythropoiesis. The reasons for this unusual shift in spleen to marrow hematopoiesis in Ames dwarf mice are yet to be determined but may relate to the decreased hormone levels in these mice.

  9. Autism-associated gene Dlgap2 mutant mice demonstrate exacerbated aggressive behaviors and orbitofrontal cortex deficits

    PubMed Central

    2014-01-01

    Background As elegant structures designed for neural communication, synapses are the building bricks of our mental functions. Recently, many studies have pointed out that synaptic protein-associated mutations may lead to dysfunctions of social cognition. Dlgap2, which encodes one of the main components of scaffold proteins in postsynaptic density (PSD), has been addressed as a candidate gene in autism spectrum disorders. To elucidate the disturbance of synaptic balance arising from Dlgap2 loss-of-function in vivo, we thus generated Dlgap2 −/− mice to investigate their phenotypes of synaptic function and social behaviors. Methods The creation of Dlgap2 −/− mice was facilitated by the recombineering-based method, Cre-loxP system and serial backcross. Reversal learning in a water T-maze was used to determine repetitive behaviors. The three-chamber approach task, resident–intruder test and tube task were performed to characterize the social behaviors of mutant mice. Cortical synaptosomal fraction, Golgi-Cox staining, whole-cell patch electrophysiology and transmission electron microscopy were all applied to investigate the function and structure of synapses in the orbitofrontal cortex (OFC) of Dlgap2 −/− mice. Results Dlgap2 −/− mice displayed exacerbated aggressive behaviors in the resident–intruder task, and elevated social dominance in the tube test. In addition, Dlgap2 −/− mice exhibited a clear reduction of receptors and scaffold proteins in cortical synapses. Dlgap2 −/− mice also demonstrated lower spine density, decreased peak amplitude of miniature excitatory postsynaptic current and ultra-structural deficits of PSD in the OFC. Conclusions Our findings clearly demonstrate that Dlgap2 plays a vital role in social behaviors and proper synaptic functions of the OFC. Moreover, these results may provide valuable insights into the neuropathology of autism. PMID:25071926

  10. Citrin/mitochondrial glycerol-3-phosphate dehydrogenase double knock-out mice recapitulate features of human citrin deficiency.

    PubMed

    Saheki, Takeyori; Iijima, Mikio; Li, Meng Xian; Kobayashi, Keiko; Horiuchi, Masahisa; Ushikai, Miharu; Okumura, Fumihiko; Meng, Xiao Jian; Inoue, Ituro; Tajima, Atsushi; Moriyama, Mitsuaki; Eto, Kazuhiro; Kadowaki, Takashi; Sinasac, David S; Tsui, Lap-Chee; Tsuji, Mihoko; Okano, Akira; Kobayashi, Tsuyoshi

    2007-08-24

    Citrin is the liver-type mitochondrial aspartate-glutamate carrier that participates in urea, protein, and nucleotide biosynthetic pathways by supplying aspartate from mitochondria to the cytosol. Citrin also plays a role in transporting cytosolic NADH reducing equivalents into mitochondria as a component of the malate-aspartate shuttle. In humans, loss-of-function mutations in the SLC25A13 gene encoding citrin cause both adult-onset type II citrullinemia and neonatal intrahepatic cholestasis, collectively referred to as human citrin deficiency. Citrin knock-out mice fail to display features of human citrin deficiency. Based on the hypothesis that an enhanced glycerol phosphate shuttle activity may be compensating for the loss of citrin function in the mouse, we have generated mice with a combined disruption of the genes for citrin and mitochondrial glycerol 3-phosphate dehydrogenase. The resulting double knock-out mice demonstrated citrullinemia, hyperammonemia that was further elevated by oral sucrose administration, hypoglycemia, and a fatty liver, all features of human citrin deficiency. An increased hepatic lactate/pyruvate ratio in the double knock-out mice compared with controls was also further elevated by the oral sucrose administration, suggesting that an altered cytosolic NADH/NAD(+) ratio is closely associated with the hyperammonemia observed. Microarray analyses identified over 100 genes that were differentially expressed in the double knock-out mice compared with wild-type controls, revealing genes potentially involved in compensatory or downstream effects of the combined mutations. Together, our data indicate that the more severe phenotype present in the citrin/mitochondrial glycerol-3-phosphate dehydrogenase double knock-out mice represents a more accurate model of human citrin deficiency than citrin knock-out mice.

  11. Aromatase Deficient Female Mice Demonstrate Altered Expression of Molecules Critical for Renal Calcium Reabsorption

    NASA Astrophysics Data System (ADS)

    Öz, Orhan K.; Hajibeigi, Asghar; Cummins, Carolyn; van Abel, Monique; Bindels, René J.; Kuro-o, Makoto; Pak, Charles Y. C.; Zerwekh, Joseph E.

    2007-04-01

    The incidence of kidney stones increases in women after the menopause, suggesting a role for estrogen deficiency. In order to determine if estrogen may be exerting an effect on renal calcium reabsorption, we measured urinary calcium excretion in the aromatase-deficient female mouse (ArKO) before and following estrogen therapy. ArKO mice had hypercalciuria that corrected during estrogen administration. To evaluate the mechanism by which estrogen deficiency leads to hypercalciuria, we examined the expression of several proteins involved in distal tubule renal calcium reabsorption, both at the message and protein levels. Messenger RNA levels of TRPV5, TRPV6, calbindin-D28K, the Na+/Ca++ exchanger (NCX1), and the plasma membrane calcium ATPase (PMCA1b) were significantly decreased in kidneys of ArKO mice. On the other hand, klotho mRNA levels were elevated in kidneys of ArKO mice. ArKO renal protein extracts had lower levels of calbindin-D28K but higher levels of the klotho protein. Immunochemistry demonstrated increased klotho expression in ArKO kidneys. Estradiol therapy normalized the expression of TRPV5, calbindin-D28K, PMCA1b and klotho. Taken together, these results demonstrate that estrogen deficiency produced by aromatase inactivation is sufficient to produce a renal leak of calcium and consequent hypercalciuria. This may represent one mechanism leading to the increased incidence of kidney stones following the menopause in women.

  12. Conditional knockout mice demonstrate function of Klf5 as a myeloid transcription factor.

    PubMed

    Shahrin, Nur Hezrin; Diakiw, Sonya; Dent, Lindsay A; Brown, Anna L; D'Andrea, Richard J

    2016-07-01

    Krüppel-like factor 5 (Klf5) encodes a zinc-finger transcription factor and has been reported to be a direct target of C/EBPα, a master transcription factor critical for formation of granulocyte-macrophage progenitors (GMP) and leukemic GMP. Using an in vivo hematopoietic-specific gene ablation model, we demonstrate that loss of Klf5 function leads to a progressive increase in peripheral white blood cells, associated with increasing splenomegaly. Long-term hematopoietic stem cells (HSCs), short-term HSCs (ST-HSCs), and multipotent progenitors (MPPs) were all significantly reduced in Klf5(Δ/Δ) mice, and knockdown of KLF5 in human CD34(+) cells suppressed colony-forming potential. ST-HSCs, MPPs, and total numbers of committed progenitors were increased in the spleen of Klf5(Δ/Δ) mice, and reduced β1- and β2-integrin expression on hematopoietic progenitors suggests that increased splenic hematopoiesis results from increased stem and progenitor mobilization. Klf5(Δ/Δ) mice show a significant reduction in the fraction of Gr1(+)Mac1(+) cells (neutrophils) in peripheral blood and bone marrow and increased frequency of eosinophils in the peripheral blood, bone marrow, and lung. Thus, these studies demonstrate dual functions of Klf5 in regulating hematopoietic stem and progenitor proliferation and localization in the bone marrow, as well as lineage choice after GMP, promoting increased neutrophil output at the expense of eosinophil production.

  13. Trim37-deficient mice recapitulate several features of the multi-organ disorder Mulibrey nanism.

    PubMed

    Kettunen, Kaisa M; Karikoski, Riitta; Hämäläinen, Riikka H; Toivonen, Teija T; Antonenkov, Vasily D; Kulesskaya, Natalia; Voikar, Vootele; Hölttä-Vuori, Maarit; Ikonen, Elina; Sainio, Kirsi; Jalanko, Anu; Karlberg, Susann; Karlberg, Niklas; Lipsanen-Nyman, Marita; Toppari, Jorma; Jauhiainen, Matti; Hiltunen, J Kalervo; Jalanko, Hannu; Lehesjoki, Anna-Elina

    2016-01-01

    Mulibrey nanism (MUL) is a rare autosomal recessive multi-organ disorder characterized by severe prenatal-onset growth failure, infertility, cardiopathy, risk for tumors, fatty liver, and type 2 diabetes. MUL is caused by loss-of-function mutations in TRIM37, which encodes an E3 ubiquitin ligase belonging to the tripartite motif (TRIM) protein family and having both peroxisomal and nuclear localization. We describe a congenic Trim37 knock-out mouse (Trim37(-/-)) model for MUL. Trim37(-/-) mice were viable and had normal weight development until approximately 12 months of age, after which they started to manifest increasing problems in wellbeing and weight loss. Assessment of skeletal parameters with computer tomography revealed significantly smaller skull size, but no difference in the lengths of long bones in Trim37(-/-) mice as compared with wild-type. Both male and female Trim37(-/-) mice were infertile, the gonads showing germ cell aplasia, hilus and Leydig cell hyperplasia and accumulation of lipids in and around Leydig cells. Male Trim37(-/-) mice had elevated levels of follicle-stimulating and luteinizing hormones, but maintained normal levels of testosterone. Six-month-old Trim37(-/-) mice had elevated fasting blood glucose and low fasting serum insulin levels. At 1.5 years Trim37(-/-) mice showed non-compaction cardiomyopathy, hepatomegaly, fatty liver and various tumors. The amount and morphology of liver peroxisomes seemed normal in Trim37(-/-) mice. The most consistently seen phenotypes in Trim37(-/-) mice were infertility and the associated hormonal findings, whereas there was more variability in the other phenotypes observed. Trim37(-/-) mice recapitulate several features of the human MUL disease and thus provide a good model to study disease pathogenesis related to TRIM37 deficiency, including infertility, non-alcoholic fatty liver disease, cardiomyopathy and tumorigenesis. PMID:27044324

  14. In vivo studies of Scn5a+/− mice modeling Brugada syndrome demonstrate both conduction and repolarization abnormalities

    PubMed Central

    Martin, Claire A.; Zhang, Yanmin; Grace, Andrew A.; Huang, Christopher L.-H.

    2010-01-01

    Objectives We investigate the extent to which the electrocardiographic (ECG) properties of intact Scn5a+/− mice reproduce the corresponding clinical Brugada syndrome phenotype and use this model to investigate the role of conduction and repolarization abnormalities in the arrhythmogenic mechanism. Methods and Results The ECGs were obtained from anesthetized wild-type and Scn5a+/− mice, before and after administration of the known pro- and antiarrhythmic agents flecainide and quinidine. The ECG intervals were measured and their dispersions calculated. Scn5a+/− hearts showed ventricular arrhythmias, ST elevation, and conduction disorders including increased QT dispersion, accentuated by flecainide. Quinidine did not cause ventricular arrhythmias but exerted variable effects on ST segments and worsened conduction abnormalities. Conclusions The ECG features in an Scn5a+/− mouse establish it as a suitable model for Brugada syndrome and demonstrate abnormal conduction and repolarization phenomena. Altered QT dispersion, taken to indicate increased transmural repolarization gradients, may be useful in clinical risk stratification. PMID:20638671

  15. Experimental demonstration of cascaded AWG access network featuring bi-directional transmission and polarization multiplexing.

    PubMed

    Tsalamanis, Ioannis; Rochat, Etienne; Walker, Stuart; Parker, Michael; Holburn, D

    2004-03-01

    We present the first experimental demonstration of a bidirectional cascaded arrayed-waveguide grating (AWG) access network combining one NxN AWG in the central office with multiple 1xN AWG's at the distribution points, such as to individually address N(2) users with only N wavelengths. Downstream and upstream data share the same optical path. BER curves were measured using 2.5Gb/s data stream in each direction, and error free transmission achieved for downstream and upstream, with only 0.3dB power penalty for simultaneous transmission. The addition of two orthogonal polarization-multiplexed channels per wavelength doubled the number of possible end users. Error free transmission was achieved with simultaneous upstream and downstream transmission of a composite signal featuring eight 2.5Gb/s channels (2 polarizations x 4 wavelengths). PMID:19474883

  16. Demonstration of Nondeclarative Sequence Learning in Mice: Development of an Animal Analog of the Human Serial Reaction Time Task

    ERIC Educational Resources Information Center

    Christie, Michael A.; Hersch, Steven M.

    2004-01-01

    In this paper, we demonstrate nondeclarative sequence learning in mice using an animal analog of the human serial reaction time task (SRT) that uses a within-group comparison of behavior in response to a repeating sequence versus a random sequence. Ten female B6CBA mice performed eleven 96-trial sessions containing 24 repetitions of a 4-trial…

  17. NPAS3 Demonstrates Features of a Tumor Suppressive Role in Driving the Progression of Astrocytomas

    PubMed Central

    Moreira, Frederico; Kiehl, Tim-Rasmus; So, Kelvin; Ajeawung, Norbert F.; Honculada, Carmelita; Gould, Peter; Pieper, Russell O.; Kamnasaran, Deepak

    2011-01-01

    Malignant astrocytomas, the most common primary brain tumors, are predominantly fatal. Improved treatments will require a better understanding of the biological features of high-grade astrocytomas. To better understand the role of neuronal PAS 3 (NPAS3) in diseases in human beings, it was investigated as a candidate for astrocytomagenesis based on the presence of aberrant protein expression in greater than 70% of a human astrocytoma panel (n = 433) and most notably in surgically resected malignant lesions. In subsequent functional studies, it was concluded that NPAS3 exhibits features of a tumor-suppressor, which drives the progression of astrocytomas by modulating the cell cycle, proliferation, apoptosis, and cell migration/invasion and has a further influence on the viability of endothelial cells. Of clinical importance, absence of NPAS3 expression in glioblastomas was a significantly negative prognostic marker of survival. In addition, malignant astrocytomas lacking NPAS3 expression demonstrated loss of function mutations, which were associated with loss of heterozygosity. While overexpressed NPAS3 in malignant glioma cell lines significantly suppressed transformation, the converse decreased expression considerably induced more aggressive growth. In addition, knockdown NPAS3 expression in a human astrocyte cell line in concert with the human papillomavirus E6 and E7 oncogenes induced growth of malignant astrocytomas. In conclusion, NPAS3 drives the progression of human malignant astrocytomas as a tumor suppressor and is a negative prognostication marker for survival. PMID:21703424

  18. Ovariectomy and 17β-estradiol replacement in rats and mice: a visual demonstration.

    PubMed

    Ström, Jakob O; Theodorsson, Annette; Ingberg, Edvin; Isaksson, Ida-Maria; Theodorsson, Elvar

    2012-01-01

    Estrogens are a family of female sexual hormones with an exceptionally wide spectrum of effects. When rats and mice are used in estrogen research they are commonly ovariectomized in order to ablate the rapidly cycling hormone production, replacing the 17β-estradiol exogenously. There is, however, lack of consensus regarding how the hormone should be administered to obtain physiological serum concentrations. This is crucial since the 17β-estradiol level/administration method profoundly influences the experimental results. We have in a series of studies characterized the different modes of 17β-estradiol administration, finding that subcutaneous silastic capsules and per-oral nut-cream Nutella are superior to commercially available slow-release pellets (produced by the company Innovative Research of America) and daily injections in terms of producing physiological serum concentrations of 17β-estradiol. Amongst the advantages of the nut-cream method, that previously has been used for buprenorphine administration, is that when used for estrogen administration it resembles peroral hormone replacement therapy and is non-invasive. The subcutaneous silastic capsules are convenient and produce the most stable serum concentrations. This video article contains step-by-step demonstrations of ovariectomy and 17β-estradiol hormone replacement by silastic capsules and peroral Nutella in rats and mice, followed by a discussion of important aspects of the administration procedures. PMID:22710371

  19. Ovariectomy and 17β-estradiol Replacement in Rats and Mice: A Visual Demonstration

    PubMed Central

    Ström, Jakob O.; Theodorsson, Annette; Ingberg, Edvin; Isaksson, Ida-Maria; Theodorsson, Elvar

    2012-01-01

    Estrogens are a family of female sexual hormones with an exceptionally wide spectrum of effects. When rats and mice are used in estrogen research they are commonly ovariectomized in order to ablate the rapidly cycling hormone production, replacing the 17β-estradiol exogenously. There is, however, lack of consensus regarding how the hormone should be administered to obtain physiological serum concentrations. This is crucial since the 17β-estradiol level/administration method profoundly influences the experimental results1-3. We have in a series of studies characterized the different modes of 17β-estradiol administration, finding that subcutaneous silastic capsules and per-oral nut-cream Nutella are superior to commercially available slow-release pellets (produced by the company Innovative Research of America) and daily injections in terms of producing physiological serum concentrations of 17β-estradiol4-6. Amongst the advantages of the nut-cream method, that previously has been used for buprenorphine administration7, is that when used for estrogen administration it resembles peroral hormone replacement therapy and is non-invasive. The subcutaneous silastic capsules are convenient and produce the most stable serum concentrations. This video article contains step-by-step demonstrations of ovariectomy and 17β-estradiol hormone replacement by silastic capsules and peroral Nutella in rats and mice, followed by a discussion of important aspects of the administration procedures. PMID:22710371

  20. Premature skin aging features rescued by inhibition of NADPH oxidase activity in XPC-deficient mice.

    PubMed

    Hosseini, Mohsen; Mahfouf, Walid; Serrano-Sanchez, Martin; Raad, Houssam; Harfouche, Ghida; Bonneu, Marc; Claverol, Stephane; Mazurier, Frederic; Rossignol, Rodrigue; Taieb, Alain; Rezvani, Hamid Reza

    2015-04-01

    Xeroderma pigmentosum type C (XP-C) is characterized mostly by a predisposition to skin cancers and accelerated photoaging, but little is known about premature skin aging in this disease. By comparing young and old mice, we found that the level of progerin and p16(INK4a) expression, β-galactosidase activity, and reactive oxygen species, which increase with age, were higher in young Xpc(-/-) mice than in young Xpc(+/+) ones. The expression level of mitochondrial complexes and mitochondrial functions in the skin of young Xpc(-/-) was as low as in control aged Xpc(+/+)animals. Furthermore, the metabolic profile in young Xpc(-/-) mice resembled that found in aged Xpc(+/+) mice. Furthermore, premature skin aging features in young Xpc(-/-) mice were mostly rescued by inhibition of nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1) activity by using a NOX1 peptide inhibitor, suggesting that the continuous oxidative stress due to overactivation of NOX1 has a causative role in the underlying pathophysiology. PMID:25437426

  1. Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever

    PubMed Central

    Oestereich, Lisa; Lüdtke, Anja; Ruibal, Paula; Pallasch, Elisa; Kerber, Romy; Rieger, Toni; Wurr, Stephanie; Bockholt, Sabrina; Krasemann, Susanne

    2016-01-01

    Lassa fever (LASF) is a highly severe viral syndrome endemic to West African countries. Despite the annual high morbidity and mortality caused by LASF, very little is known about the pathophysiology of the disease. Basic research on LASF has been precluded due to the lack of relevant small animal models that reproduce the human disease. Immunocompetent laboratory mice are resistant to infection with Lassa virus (LASV) and, to date, only immunodeficient mice, or mice expressing human HLA, have shown some degree of susceptibility to experimental infection. Here, transplantation of wild-type bone marrow cells into irradiated type I interferon receptor knockout mice (IFNAR-/-) was used to generate chimeric mice that reproduced important features of severe LASF in humans. This included high lethality, liver damage, vascular leakage and systemic virus dissemination. In addition, this model indicated that T cell-mediated immunopathology was an important component of LASF pathogenesis that was directly correlated with vascular leakage. Our strategy allows easy generation of a suitable small animal model to test new vaccines and antivirals and to dissect the basic components of LASF pathophysiology. PMID:27191716

  2. Trim37-deficient mice recapitulate several features of the multi-organ disorder Mulibrey nanism

    PubMed Central

    Kettunen, Kaisa M.; Karikoski, Riitta; Hämäläinen, Riikka H.; Toivonen, Teija T.; Antonenkov, Vasily D.; Kulesskaya, Natalia; Voikar, Vootele; Hölttä-Vuori, Maarit; Ikonen, Elina; Sainio, Kirsi; Jalanko, Anu; Karlberg, Susann; Karlberg, Niklas; Lipsanen-Nyman, Marita; Toppari, Jorma; Jauhiainen, Matti; Hiltunen, J. Kalervo; Jalanko, Hannu; Lehesjoki, Anna-Elina

    2016-01-01

    ABSTRACT Mulibrey nanism (MUL) is a rare autosomal recessive multi-organ disorder characterized by severe prenatal-onset growth failure, infertility, cardiopathy, risk for tumors, fatty liver, and type 2 diabetes. MUL is caused by loss-of-function mutations in TRIM37, which encodes an E3 ubiquitin ligase belonging to the tripartite motif (TRIM) protein family and having both peroxisomal and nuclear localization. We describe a congenic Trim37 knock-out mouse (Trim37−/−) model for MUL. Trim37−/− mice were viable and had normal weight development until approximately 12 months of age, after which they started to manifest increasing problems in wellbeing and weight loss. Assessment of skeletal parameters with computer tomography revealed significantly smaller skull size, but no difference in the lengths of long bones in Trim37−/− mice as compared with wild-type. Both male and female Trim37−/− mice were infertile, the gonads showing germ cell aplasia, hilus and Leydig cell hyperplasia and accumulation of lipids in and around Leydig cells. Male Trim37−/− mice had elevated levels of follicle-stimulating and luteinizing hormones, but maintained normal levels of testosterone. Six-month-old Trim37−/− mice had elevated fasting blood glucose and low fasting serum insulin levels. At 1.5 years Trim37−/− mice showed non-compaction cardiomyopathy, hepatomegaly, fatty liver and various tumors. The amount and morphology of liver peroxisomes seemed normal in Trim37−/− mice. The most consistently seen phenotypes in Trim37−/− mice were infertility and the associated hormonal findings, whereas there was more variability in the other phenotypes observed. Trim37−/− mice recapitulate several features of the human MUL disease and thus provide a good model to study disease pathogenesis related to TRIM37 deficiency, including infertility, non-alcoholic fatty liver disease, cardiomyopathy and tumorigenesis. PMID:27044324

  3. C9orf72 BAC Transgenic Mice Display Typical Pathologic Features of ALS/FTD.

    PubMed

    O'Rourke, Jacqueline G; Bogdanik, Laurent; Muhammad, A K M G; Gendron, Tania F; Kim, Kevin J; Austin, Andrew; Cady, Janet; Liu, Elaine Y; Zarrow, Jonah; Grant, Sharday; Ho, Ritchie; Bell, Shaughn; Carmona, Sharon; Simpkinson, Megan; Lall, Deepti; Wu, Kathryn; Daughrity, Lillian; Dickson, Dennis W; Harms, Matthew B; Petrucelli, Leonard; Lee, Edward B; Lutz, Cathleen M; Baloh, Robert H

    2015-12-01

    Noncoding expansions of a hexanucleotide repeat (GGGGCC) in the C9orf72 gene are the most common cause of familial amyotrophic lateral sclerosis and frontotemporal dementia. Here we report transgenic mice carrying a bacterial artificial chromosome (BAC) containing the full human C9orf72 gene with either a normal allele (15 repeats) or disease-associated expansion (∼100-1,000 repeats; C9-BACexp). C9-BACexp mice displayed pathologic features seen in C9orf72 expansion patients, including widespread RNA foci and repeat-associated non-ATG (RAN) translated dipeptides, which were suppressed by antisense oligonucleotides targeting human C9orf72. Nucleolin distribution was altered, supporting that either C9orf72 transcripts or RAN dipeptides promote nucleolar dysfunction. Despite early and widespread production of RNA foci and RAN dipeptides in C9-BACexp mice, behavioral abnormalities and neurodegeneration were not observed even at advanced ages, supporting the hypothesis that RNA foci and RAN dipeptides occur presymptomatically and are not sufficient to drive neurodegeneration in mice at levels seen in patients. PMID:26637796

  4. Do Linguistic Features of Science Test Items Prevent English Language Learners from Demonstrating Their Knowledge?

    ERIC Educational Resources Information Center

    Noble, Tracy; Kachchaf, Rachel; Rosebery, Ann; Warren, Beth; O'Connor, Mary Catherine; Wang, Yang

    2014-01-01

    Little research has examined individual linguistic features that influence English language learners (ELLs) test performance. Furthermore, research has yet to explore the relationship between the science strand of test items and the types of linguistic features the items include. Utilizing Differential Item Functioning, this study examines ELL…

  5. Behavioral phenotyping of Parkin-deficient mice: looking for early preclinical features of Parkinson's disease.

    PubMed

    Rial, Daniel; Castro, Adalberto A; Machado, Nuno; Garção, Pedro; Gonçalves, Francisco Q; Silva, Henrique B; Tomé, Angelo R; Köfalvi, Attila; Corti, Olga; Raisman-Vozari, Rita; Cunha, Rodrigo A; Prediger, Rui D

    2014-01-01

    There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson's disease (PD) begin many years before the appearance of the characteristic motor symptoms. Neuropsychiatric, sensorial and cognitive deficits are recognized as early non-motor manifestations of PD, and are not attenuated by the current anti-parkinsonian therapy. Although loss-of-function mutations in the parkin gene cause early-onset familial PD, Parkin-deficient mice do not display spontaneous degeneration of the nigrostriatal pathway or enhanced vulnerability to dopaminergic neurotoxins such as 6-OHDA and MPTP. Here, we employed adult homozygous C57BL/6 mice with parkin gene deletion on exon 3 (parkin-/-) to further investigate the relevance of Parkin in the regulation of non-motor features, namely olfactory, emotional, cognitive and hippocampal synaptic plasticity. Parkin-/- mice displayed normal performance on behavioral tests evaluating olfaction (olfactory discrimination), anxiety (elevated plus-maze), depressive-like behavior (forced swimming and tail suspension) and motor function (rotarod, grasping strength and pole). However, parkin-/- mice displayed a poor performance in the open field habituation, object location and modified Y-maze tasks suggestive of procedural and short-term spatial memory deficits. These behavioral impairments were accompanied by impaired hippocampal long-term potentiation (LTP). These findings indicate that the genetic deletion of parkin causes deficiencies in hippocampal synaptic plasticity, resulting in memory deficits with no major olfactory, emotional or motor impairments. Therefore, parkin-/- mice may represent a promising animal model to study the early stages of PD and for testing new therapeutic strategies to restore learning and memory and synaptic plasticity impairments in PD. PMID:25486126

  6. Loss of distal axons and sensory Merkel cells and features indicative of muscle denervation in hindlimbs of P0-deficient mice.

    PubMed

    Frei, R; Mötzing, S; Kinkelin, I; Schachner, M; Koltzenburg, M; Martini, R

    1999-07-15

    Mice lacking the major Schwann cell myelin component P0 show a severe dysmyelination with pathological features reminiscent of the Déjérine-Sottas syndrome in humans. Previous morphological and electrophysiological studies on these mice did not only demonstrate a compromised myelination and myelin maintenance, but were suggestive of an impairment of axons as well. Here, we studied the axonal pathology in P0-deficient mice by quantitative electron microscopy. In addition, we investigated epidermal receptor end organs by immunocytochemistry and muscle pathology by histochemistry. In proximal sections of facial and femoral nerves, axon calibers were significantly reduced, whereas the number of myelin-competent axons was not diminished in 5- and 17-month-old P0-deficient mice. However, in distal branches of the femoral and sciatic nerve (digital nerves innervating the skin of the first toe) the numbers of myelin-competent axons were reduced by 70% in 6-month-old P0-deficient mice. Immunolabeling of foot pads revealed a corresponding loss of Merkel cells by 75%, suggesting that survival of these cells is dependent on the presence or maintenance of their innervating myelinated axons. In addition, quadriceps and gastrocnemius muscles showed pathological features indicative of denervation and axonal sprouting. These findings demonstrate that loss of an important myelin component can initiate degenerative mechanisms not only in the Schwann cell but also in the distal portions of myelinated axons, leading to the degeneration of specialized receptor end organs and impairment of muscle innervation. PMID:10407042

  7. Immunohistochemical demonstration of epidermal growth factor in human gastric cancer xenografts of nude mice.

    PubMed

    Yoshiyuki, T; Shimizu, Y; Onda, M; Tokunaga, A; Kiyama, T; Nishi, K; Mizutani, T; Matsukura, N; Tanaka, N; Akimoto, M

    1990-02-15

    Thirty-two surgical specimens and three cell lines of human gastric cancers were used for subcutaneous transplantation into nude mice, resulting in the establishment of eight (25%) xenografts from the surgical specimens and two (67%) from the cell lines. The localization of epidermal growth factor (EGF) in the surgical specimens and cell lines of the gastric cancers and their xenografts in nude mice was then investigated immunohistochemically. Epidermal growth factor was stained in the cytoplasm of the cancer cells, being detected in 16 (50%) of the 32 surgical specimens and in all of the cell lines. Seven (44%) of the sixteen EGF-positive surgical specimens and one (6%) of the 16 EGF-negative ones were tumorigenic in nude mice. All of the xenografts in nude mice were positive for EGF. The tumorigenicity of human gastric cancer xenografts in nude mice may, therefore, be correlated with the presence of EGF in cancer cells.

  8. Compared with DBA/2J mice, C57BL/6J mice demonstrate greater preference for saccharin and less avoidance of a cocaine-paired saccharin cue.

    PubMed

    Freet, Christopher S; Arndt, Amanda; Grigson, Patricia S

    2013-06-01

    Rats avoid intake of a saccharin cue when paired with a drug of abuse. While this is true for most subjects, the degree of avoidance of the drug-paired cue depends upon many factors including an individual rat's preference for rewards. That said, the direction of this effect is complex. For example, reward-preferring Lewis rats exhibit greater cocaine-induced avoidance of a saccharin cue relative to Fischer 344 rats; while reward-preferring mice that overexpress ΔFosB (NSE-tTA × TetOp-ΔFosB) exhibit less avoidance of the drug-paired taste cue compared to controls. The aim here was to use two strains of commonly used mice, C57BL/6J and DBA/2J, to determine whether known differences in sensitivity to rewards will facilitate or attenuate drug-induced suppression of intake of a drug-paired taste cue. The results of Experiment 1 demonstrate that C57BL/6J mice, compared with DBA/2J mice, exhibit attenuated suppression of saccharin intake when it is paired with cocaine. The results of Experiment 2 demonstrate that strain differences in impulsivity are not likely to account for these differences. It is proposed that, while the C57BL/6J mice typically are more responsive to drug, they also are more responsive to natural rewards (in this case saccharin), and the stronger preference for saccharin serves to militate against drug.

  9. Senescence induced by RECQL4 dysfunction contributes to Rothmund-Thomson syndrome features in mice.

    PubMed

    Lu, H; Fang, E F; Sykora, P; Kulikowicz, T; Zhang, Y; Becker, K G; Croteau, D L; Bohr, V A

    2014-05-15

    Cellular senescence refers to irreversible growth arrest of primary eukaryotic cells, a process thought to contribute to aging-related degeneration and disease. Deficiency of RecQ helicase RECQL4 leads to Rothmund-Thomson syndrome (RTS), and we have investigated whether senescence is involved using cellular approaches and a mouse model. We first systematically investigated whether depletion of RECQL4 and the other four human RecQ helicases, BLM, WRN, RECQL1 and RECQL5, impacts the proliferative potential of human primary fibroblasts. BLM-, WRN- and RECQL4-depleted cells display increased staining of senescence-associated β-galactosidase (SA-β-gal), higher expression of p16(INK4a) or/and p21(WAF1) and accumulated persistent DNA damage foci. These features were less frequent in RECQL1- and RECQL5-depleted cells. We have mapped the region in RECQL4 that prevents cellular senescence to its N-terminal region and helicase domain. We further investigated senescence features in an RTS mouse model, Recql4-deficient mice (Recql4(HD)). Tail fibroblasts from Recql4(HD) showed increased SA-β-gal staining and increased DNA damage foci. We also identified sparser tail hair and fewer blood cells in Recql4(HD) mice accompanied with increased senescence in tail hair follicles and in bone marrow cells. In conclusion, dysfunction of RECQL4 increases DNA damage and triggers premature senescence in both human and mouse cells, which may contribute to symptoms in RTS patients.

  10. Angiography reveals novel features of the retinal vasculature in healthy and diabetic mice.

    PubMed

    McLenachan, Samuel; Magno, Aaron Len; Ramos, David; Catita, Joana; McMenamin, Paul G; Chen, Fred Kuanfu; Rakoczy, Elizabeth Piroska; Ruberte, Jesus

    2015-09-01

    The mouse retina is a commonly used animal model for the study of pathogenesis and treatment of blinding retinal vascular diseases such as diabetic retinopathy. In this study, we aimed to characterize normal and pathological variations in vascular anatomy in the mouse retina using fluorescein angiography visualized with scanning laser ophthalmoscopy and optical coherence tomography (SLO-OCT). We examined eyes from C57BL/6J wild type mice as well as the Ins2(Akita) and Akimba mouse models of diabetic retinopathy using the Heidelberg Retinal Angiography (HRA) and OCT system. Angiography was performed on three focal planes to examine distinct vascular layers. For comparison with angiographic data, ex vivo analyses, including Indian ink angiography, histology and 3D confocal scanning laser microscopy were performed in parallel. All layers of the mouse retinal vasculature could be readily visualized during fluorescein angiography by SLO-OCT. Blood vessel density was increased in the deep vascular plexus (DVP) compared with the superficial vascular plexus (SVP). Arteriolar and venular typologies were established and structural differences were observed between venular types. Unexpectedly, the hyaloid artery was found to persist in 15% of C57BL/6 mice, forming anastomoses with peripheral retinal capillaries. Fluorescein leakage was easily detected in Akimba retinae by angiography, but was not observed in Ins2(Akita) mice. Blood vessel density was increased in the DVP of 6 month old Ins2(Akita) mice, while the SVP displayed reduced branching in precapillary arterioles. In summary, we present the first comprehensive characterization of the mouse retinal vasculature by SLO-OCT fluorescein angiography. Using this clinical imaging technique, we report previously unrecognized variations in C57BL/6J vascular anatomy and novel features of vascular retinopathy in the Ins2(Akita) mouse model of diabetes.

  11. The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension.

    PubMed

    Gembardt, Florian; Bartaun, Christoph; Jarzebska, Natalia; Mayoux, Eric; Todorov, Vladimir T; Hohenstein, Bernd; Hugo, Christian

    2014-08-01

    Diabetic nephropathy is the leading cause of end-stage renal disease in humans in the Western world. The recent development of Na+-glucose cotransporter 2 (SGLT2) inhibitors offers a new antidiabetic therapy via enhanced glucose excretion. Whether this strategy exerts beneficial effects on the development of type 2 diabetic nephropathy is still largely unclear. We investigated the effects of the specific SGLT2 inhibitor empagliflozin in BTBR.Cg-Lep/WiscJ (BTBR ob/ob) mice, which spontaneously develop type 2 diabetic nephropathy. In the first experiment, BTBR ob/ob mice received either a diet containing 300 ppm empagliflozin or equicaloric placebo chow for 12 wk. In the second experiment, BTBR ob/ob mice received 1 μg·kg body wt(-1)·day(-1) ANG II to induce arterial hypertension and were separated into the same two diet groups for 6 wk. In both experiments, empagliflozin treatment enhanced glucosuria, thereby lowering blood glucose. Independently of hypertension, empagliflozin reduced albuminuria in diabetic mice. However, empagliflozin treatment affected diabetes-related glomerular hypertrophy, markers of renal inflammation, and mesangial matrix expansion only in BTBR ob/ob mice without hypertension. In summary, empagliflozin demonstrated significant antihyperglycemic effects, differentially ameliorating early features of diabetic nephropathy in BTBR ob/ob mice with and without hypertension.

  12. Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice

    PubMed Central

    Pai, Yun Jin; Leung, Kit-Yi; Savery, Dawn; Hutchin, Tim; Prunty, Helen; Heales, Simon; Brosnan, Margaret E.; Brosnan, John T.; Copp, Andrew J.; Greene, Nicholas D.E.

    2015-01-01

    Glycine decarboxylase (GLDC) acts in the glycine cleavage system to decarboxylate glycine and transfer a one-carbon unit into folate one-carbon metabolism. GLDC mutations cause a rare recessive disease non-ketotic hyperglycinemia (NKH). Mutations have also been identified in patients with neural tube defects (NTDs); however, the relationship between NKH and NTDs is unclear. We show that reduced expression of Gldc in mice suppresses glycine cleavage system activity and causes two distinct disease phenotypes. Mutant embryos develop partially penetrant NTDs while surviving mice exhibit post-natal features of NKH including glycine accumulation, early lethality and hydrocephalus. In addition to elevated glycine, Gldc disruption also results in abnormal tissue folate profiles, with depletion of one-carbon-carrying folates, as well as growth retardation and reduced cellular proliferation. Formate treatment normalizes the folate profile, restores embryonic growth and prevents NTDs, suggesting that Gldc deficiency causes NTDs through limiting supply of one-carbon units from mitochondrial folate metabolism. PMID:25736695

  13. Urokinase plasminogen activator receptor-deficient mice demonstrate reduced hyperoxia-induced lung injury.

    PubMed

    van Zoelen, Marieke A D; Florquin, Sandrine; de Beer, Regina; Pater, Jennie M; Verstege, Marleen I; Meijers, Joost C M; van der Poll, Tom

    2009-06-01

    Patients with respiratory failure often require supplemental oxygen therapy and mechanical ventilation. Although both supportive measures are necessary to guarantee adequate oxygen uptake, they can also cause or worsen lung inflammation and injury. Hyperoxia-induced lung injury is characterized by neutrophil infiltration into the lungs. The urokinase plasminogen activator receptor (uPAR) has been deemed important for leukocyte trafficking. To determine the expression and function of neutrophil uPAR during hyperoxia-induced lung injury, uPAR expression was determined on pulmonary neutrophils of mice exposed to hyperoxia. Hyperoxia exposure (O2>80%) for 4 days elicited a pulmonary inflammatory response as reflected by a profound rise in the number of neutrophils that were recovered from bronchoalveolar lavage fluid and lung cell suspensions, as well as increased bronchoalveolar keratinocyte-derived chemokine, interleukin-6, total protein, and alkaline phosphatase levels. In addition, hyperoxia induced the migration of uPAR-positive granulocytes into lungs from wild-type mice compared with healthy control mice (exposed to room air). uPAR deficiency was associated with diminished neutrophil influx into both lung tissues and bronchoalveolar spaces, which was accompanied by a strong reduction in lung injury. Furthermore, in uPAR(-/-) mice, activation of coagulation was diminished. These data suggest that uPAR plays a detrimental role in hyperoxia-induced lung injury and that uPAR deficiency is associated with diminished neutrophil influx into both lung tissues and bronchoalveolar spaces, accompanied by decreased pulmonary injury. PMID:19435793

  14. Cushing's syndrome and fetal features resurgence in adrenal cortex-specific Prkar1a knockout mice.

    PubMed

    Sahut-Barnola, Isabelle; de Joussineau, Cyrille; Val, Pierre; Lambert-Langlais, Sarah; Damon, Christelle; Lefrançois-Martinez, Anne-Marie; Pointud, Jean-Christophe; Marceau, Geoffroy; Sapin, Vincent; Tissier, Frédérique; Ragazzon, Bruno; Bertherat, Jérôme; Kirschner, Lawrence S; Stratakis, Constantine A; Martinez, Antoine

    2010-06-01

    Carney complex (CNC) is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent endocrine manifestation is primary pigmented nodular adrenocortical disease (PPNAD), a bilateral adrenocortical hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, a gene encoding the type 1 alpha-regulatory subunit (R1alpha) of the cAMP-dependent protein kinase (PKA) have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1alpha loss in the initiation and development of PPNAD, we generated mice lacking Prkar1a specifically in the adrenal cortex (AdKO). AdKO mice develop pituitary-independent Cushing's syndrome with increased PKA activity. This leads to autonomous steroidogenic genes expression and deregulated adreno-cortical cells differentiation, increased proliferation and resistance to apoptosis. Unexpectedly, R1alpha loss results in improper maintenance and centrifugal expansion of cortisol-producing fetal adrenocortical cells with concomitant regression of adult cortex. Our data provide the first in vivo evidence that loss of R1alpha is sufficient to induce autonomous adrenal hyper-activity and bilateral hyperplasia, both observed in human PPNAD. Furthermore, this model demonstrates that deregulated PKA activity favors the emergence of a new cell population potentially arising from the fetal adrenal, giving new insight into the mechanisms leading to PPNAD. PMID:20548949

  15. Tears of the fascia cruris demonstrate characteristic sonographic features: a case series analysis

    PubMed Central

    Morton, Sarah; Chan, Otto; Webborn, Nick; Pritchard, Melanie; Morrissey, Dylan

    2015-01-01

    Summary Background fascia cruris (FC) tears have recently been recognised in the literature, although little is known about their characteristic ultrasound findings. The aim was to describe the echo-graphic features of FC tears in order to improve recognition and diagnosis. Methods the ultrasound reports and images of >600 patients attending a specialist musculoskeletal clinic for Achilles tendon ultrasound scans between October 2010–May 2014 were reviewed. Any patient diagnosed with a FC tear had a structured data set extracted. All ultrasound images were performed by one consultant radiologist. Bilateral Achilles images were available for analysis. Results sixteen patients from >600 subjects were diagnosed with a FC tear. Fourteen subjects were male and two female (mean age 37.8; range 23–61), with seven elite level sports men. Nine tears were right sided and seven left, with eight situated laterally and seven medially. Seven of the tears were situated in the musculotendinous junction. Symptomatic Achilles tendinopathy co-existed in ten of sixteen subjects (average transverse diameter of Achilles tendon = 7.1±2.0 mm). Conclusion FC tears should be considered in the differential diagnoses for Achillodynia, diagnosed using their characteristic ultrasound findings, with a hypoechoic area at the medial or lateral attachment to the Achilles tendon in the transverse plane. PMID:26958540

  16. MRL/MpJ mice show unique pathological features after experimental kidney injury.

    PubMed

    Shiozuru, Daichi; Ichii, Osamu; Kimura, Junpei; Nakamura, Teppei; Elewa, Yaser Hosny Ali; Otsuka-Kanazawa, Saori; Kon, Yasuhiro

    2016-02-01

    Clarification of the renal repair process is crucial for developing novel therapeutic strategies for kidney injury. MRL/MpJ mice have a unique repair process characterized by low scar formation. The pathological features of experimentally injured MRL/MpJ and C57BL/6 mouse kidneys were compared to examine the renal repair process. The dilation and atrophy of renal tubules were observed in folic acid (FA)-induced acute kidney injury (AKI) in both strains, and the histopathological injury scores and number of interleukin (IL)-1F6-positive damaged distal tubules and kidney injury molecule 1 (KIM-1)-positive damaged proximal tubules drastically increased 1 day after AKI induction. However, KIM-1-positive tubules and the elevation of serum renal function markers were significantly fewer and lower, respectively, in MRL/MpJ mice at days 2 and 7 after AKI. After traumatic kidney injury (TKI) via needle puncture, severe tubular necrotic lesions in the punctured area and fibrosis progressed in both strains. Indices for fibrosis such as aniline blue-positive area, number of alpha smooth muscle actin-positive myofibroblasts, and messenger RNA expression levels of Tgfb1 and Mmp2 indicated lower fibrotic activity in MRL/MpJ kidneys. Characteristically, only MRL/MpJ kidneys manifested remarkable calcification around the punctured area beginning 7 days after TKI. The pathological features of injured MRL/MpJ and C57BL/6 kidneys differed, especially those of kidneys with mild proximal tubular injuries after FA-induced AKI. Lower fibrotic activity and increased calcification after TKI were observed in MRL/MpJ kidneys. These findings clarified the unique pathological characteristics of MRL/MpJ mouse kidneys and contribute to understanding of the renal repair process after kidney injury.

  17. Graphene-augmented nanofiber scaffolds demonstrate new features in cells behaviour.

    PubMed

    Kazantseva, Jekaterina; Ivanov, Roman; Gasik, Michael; Neuman, Toomas; Hussainova, Irina

    2016-01-01

    Three-dimensional (3D) customized scaffolds capable to mimic a native extracellular matrix open new frontiers in cells manipulation and advanced therapy. The major challenge is in a proper substrate for in vitro models on engineered scaffolds, capable to modulate cells differentiation. Here for the first time we demonstrate novel design and functionality of the 3D porous scaffolds of aligned, self-assembled ceramic nanofibers of ultra-high anisotropy ratio (~10(7)), augmented into graphene shells. This unique hybrid nano-network allows an exceptional combination of selective guidance stimuli of stem cells differentiation, immune reactions variations, and local immobilization of cancer cells, which was not available before. The scaffolds were shown to be able to direct human mesenchymal stem cells (important for stimulation of neuronal and muscle cells) preferential orientation, to suppress major inflammatory factors, and to localize cancer cells; all without additions of specific culture media. The selective downregulation of specific cytokines is anticipated as a new tool for understanding of human immune system and ways of treatment of associated diseases. The effects observed are self-regulated by cells only, without side effects, usually arising from use of external factors. New scaffolds may open new horizons for stem cells fate control such as towards axons and neurites regeneration (Alzheimer's disease) as well as cancer therapy development. PMID:27443974

  18. Graphene-augmented nanofiber scaffolds demonstrate new features in cells behaviour

    PubMed Central

    Kazantseva, Jekaterina; Ivanov, Roman; Gasik, Michael; Neuman, Toomas; Hussainova, Irina

    2016-01-01

    Three-dimensional (3D) customized scaffolds capable to mimic a native extracellular matrix open new frontiers in cells manipulation and advanced therapy. The major challenge is in a proper substrate for in vitro models on engineered scaffolds, capable to modulate cells differentiation. Here for the first time we demonstrate novel design and functionality of the 3D porous scaffolds of aligned, self-assembled ceramic nanofibers of ultra-high anisotropy ratio (~107), augmented into graphene shells. This unique hybrid nano-network allows an exceptional combination of selective guidance stimuli of stem cells differentiation, immune reactions variations, and local immobilization of cancer cells, which was not available before. The scaffolds were shown to be able to direct human mesenchymal stem cells (important for stimulation of neuronal and muscle cells) preferential orientation, to suppress major inflammatory factors, and to localize cancer cells; all without additions of specific culture media. The selective downregulation of specific cytokines is anticipated as a new tool for understanding of human immune system and ways of treatment of associated diseases. The effects observed are self-regulated by cells only, without side effects, usually arising from use of external factors. New scaffolds may open new horizons for stem cells fate control such as towards axons and neurites regeneration (Alzheimer’s disease) as well as cancer therapy development. PMID:27443974

  19. Graphene-augmented nanofiber scaffolds demonstrate new features in cells behaviour

    NASA Astrophysics Data System (ADS)

    Kazantseva, Jekaterina; Ivanov, Roman; Gasik, Michael; Neuman, Toomas; Hussainova, Irina

    2016-07-01

    Three-dimensional (3D) customized scaffolds capable to mimic a native extracellular matrix open new frontiers in cells manipulation and advanced therapy. The major challenge is in a proper substrate for in vitro models on engineered scaffolds, capable to modulate cells differentiation. Here for the first time we demonstrate novel design and functionality of the 3D porous scaffolds of aligned, self-assembled ceramic nanofibers of ultra-high anisotropy ratio (~107), augmented into graphene shells. This unique hybrid nano-network allows an exceptional combination of selective guidance stimuli of stem cells differentiation, immune reactions variations, and local immobilization of cancer cells, which was not available before. The scaffolds were shown to be able to direct human mesenchymal stem cells (important for stimulation of neuronal and muscle cells) preferential orientation, to suppress major inflammatory factors, and to localize cancer cells; all without additions of specific culture media. The selective downregulation of specific cytokines is anticipated as a new tool for understanding of human immune system and ways of treatment of associated diseases. The effects observed are self-regulated by cells only, without side effects, usually arising from use of external factors. New scaffolds may open new horizons for stem cells fate control such as towards axons and neurites regeneration (Alzheimer’s disease) as well as cancer therapy development.

  20. Norepinephrine transporter variant A457P knock-in mice display key features of human postural orthostatic tachycardia syndrome.

    PubMed

    Shirey-Rice, Jana K; Klar, Rebecca; Fentress, Hugh M; Redmon, Sarah N; Sabb, Tiffany R; Krueger, Jessica J; Wallace, Nathan M; Appalsamy, Martin; Finney, Charlene; Lonce, Suzanna; Diedrich, André; Hahn, Maureen K

    2013-07-01

    Postural orthostatic tachycardia syndrome (POTS) is a common autonomic disorder of largely unknown etiology that presents with sustained tachycardia on standing, syncope and elevated norepinephrine spillover. Some individuals with POTS experience anxiety, depression and cognitive dysfunction. Previously, we identified a mutation, A457P, in the norepinephrine (NE; also known as noradrenaline) transporter (NET; encoded by SLC6A2) in POTS patients. NET is expressed at presynaptic sites in NE neurons and plays a crucial role in regulating NE signaling and homeostasis through NE reuptake into noradrenergic nerve terminals. Our in vitro studies demonstrate that A457P reduces both NET surface trafficking and NE transport and exerts a dominant-negative impact on wild-type NET proteins. Here we report the generation and characterization of NET A457P mice, demonstrating the ability of A457P to drive the POTS phenotype and behaviors that are consistent with reported comorbidities. Mice carrying one A457P allele (NET(+/P)) exhibited reduced brain and sympathetic NE transport levels compared with wild-type (NET(+/+)) mice, whereas transport activity in mice carrying two A457P alleles (NET(P/P)) was nearly abolished. NET(+/P) and NET(P/P) mice exhibited elevations in plasma and urine NE levels, reduced 3,4-dihydroxyphenylglycol (DHPG), and reduced DHPG:NE ratios, consistent with a decrease in sympathetic nerve terminal NE reuptake. Radiotelemetry in unanesthetized mice revealed tachycardia in NET(+/P) mice without a change in blood pressure or baroreceptor sensitivity, consistent with studies of human NET A457P carriers. NET(+/P) mice also demonstrated behavioral changes consistent with CNS NET dysfunction. Our findings support that NET dysfunction is sufficient to produce a POTS phenotype and introduces the first genetic model suitable for more detailed mechanistic studies of the disorder and its comorbidities.

  1. Role of Muscarinic Acetylcholine Receptors in Serial Feature-Positive Discrimination Task during Eyeblink Conditioning in Mice.

    PubMed

    Rahman, Md Ashrafur; Tanaka, Norifumi; Usui, Koji; Kawahara, Shigenori

    2016-01-01

    We investigated the role of muscarinic acetylcholine receptors (mAChRs) in eyeblink serial feature-positive discrimination learning in mice using the mAChR antagonist. A 2-s light cue was delivered 5 or 6 s before the presentation of a 350-ms tone paired with a 100-ms periorbital electrical shock (cued trial) but not before the tone-alone presentation (non-cued trial). Mice received 30 cued and 30 non-cued trials each day in a random order. We found that saline-injected control mice were successfully discriminating between cued and non-cued trials within a few days of conditioning. The mice responded more frequently to the tone in cued trials than in non-cued trials. Analysis of conditioned response (CR) dynamics revealed that the CR onset latency was shorter in cued trials than in non-cued trials, despite the CR peak amplitude not differing significantly between the two conditions. In contrast, scopolamine-injected mice developed an equal number of CRs with similar temporal patterns irrespective of the presence of the cue during the 7 days of conditioning, indicating in a failure to acquire conditional discrimination. In addition, the scopolamine administration to the control mice after they had successfully acquired discrimination did not impair the conditional discrimination and expression of pre-acquired CR. These results suggest that mAChRs may play a pivotal role in memory formation in the conditional brain state associated with the feature cue; however they are unlikely to be involved in the development of discrimination after conditional memory had formed in the serial feature-positive discrimination task during eyeblink conditioning. PMID:26808980

  2. Role of Muscarinic Acetylcholine Receptors in Serial Feature-Positive Discrimination Task during Eyeblink Conditioning in Mice

    PubMed Central

    Rahman, Md. Ashrafur; Tanaka, Norifumi; Usui, Koji; Kawahara, Shigenori

    2016-01-01

    We investigated the role of muscarinic acetylcholine receptors (mAChRs) in eyeblink serial feature-positive discrimination learning in mice using the mAChR antagonist. A 2-s light cue was delivered 5 or 6 s before the presentation of a 350-ms tone paired with a 100-ms periorbital electrical shock (cued trial) but not before the tone-alone presentation (non-cued trial). Mice received 30 cued and 30 non-cued trials each day in a random order. We found that saline-injected control mice were successfully discriminating between cued and non-cued trials within a few days of conditioning. The mice responded more frequently to the tone in cued trials than in non-cued trials. Analysis of conditioned response (CR) dynamics revealed that the CR onset latency was shorter in cued trials than in non-cued trials, despite the CR peak amplitude not differing significantly between the two conditions. In contrast, scopolamine-injected mice developed an equal number of CRs with similar temporal patterns irrespective of the presence of the cue during the 7 days of conditioning, indicating in a failure to acquire conditional discrimination. In addition, the scopolamine administration to the control mice after they had successfully acquired discrimination did not impair the conditional discrimination and expression of pre-acquired CR. These results suggest that mAChRs may play a pivotal role in memory formation in the conditional brain state associated with the feature cue; however they are unlikely to be involved in the development of discrimination after conditional memory had formed in the serial feature-positive discrimination task during eyeblink conditioning. PMID:26808980

  3. [DEMONSTRATION OF LIKELIHOOD OF THE NEGATIVE EFFECT OF PHYSICAL PROTECTION DURING TOTAL PROTON IRRADIATION OF MICE].

    PubMed

    Ivanov, A A; Bulynina, T M; Molokanov, A G; Vorozhtsova, S V; Utina, D M; Severyukhin, Yu S; Ushakov, I B

    2015-01-01

    The experiments were performed with outbred CD-1 male mice (SPF category). Total irradiation at 1.0; 2.5 and 5.0 Gy by protons with the average energy of 170 MeV was conducted in a level medical beam of the phasotron at the Joint Institute of Nuclear Investigations. Targets were 2 points of in-depth dose distribution, i.e. beam entrance of the object, and modified Bragg peak. As a physical protector, the comb filter increases linear energy transfer (LET) of 170 MeV entrance protons from 0.49 keV/μm to 1.6 keV/μm and, according to the bone marrow test, doubles the biological effectiveness of protons when comparing radiation doses that cause 37% inhibition of blood cell formation in the bone marrow. Physical protection increases dose rate from 0.37 Gy/min for entrance protons to 0.8 Gy/min for moderated protons which more than in thrice reduces time of irradiation needed to reach an equal radiobiological effect.

  4. [DEMONSTRATION OF LIKELIHOOD OF THE NEGATIVE EFFECT OF PHYSICAL PROTECTION DURING TOTAL PROTON IRRADIATION OF MICE].

    PubMed

    Ivanov, A A; Bulynina, T M; Molokanov, A G; Vorozhtsova, S V; Utina, D M; Severyukhin, Yu S; Ushakov, I B

    2015-01-01

    The experiments were performed with outbred CD-1 male mice (SPF category). Total irradiation at 1.0; 2.5 and 5.0 Gy by protons with the average energy of 170 MeV was conducted in a level medical beam of the phasotron at the Joint Institute of Nuclear Investigations. Targets were 2 points of in-depth dose distribution, i.e. beam entrance of the object, and modified Bragg peak. As a physical protector, the comb filter increases linear energy transfer (LET) of 170 MeV entrance protons from 0.49 keV/μm to 1.6 keV/μm and, according to the bone marrow test, doubles the biological effectiveness of protons when comparing radiation doses that cause 37% inhibition of blood cell formation in the bone marrow. Physical protection increases dose rate from 0.37 Gy/min for entrance protons to 0.8 Gy/min for moderated protons which more than in thrice reduces time of irradiation needed to reach an equal radiobiological effect. PMID:26554131

  5. Gender features and estrous cycle variations of nocturnal behavior of mice after a single exposure to light at night.

    PubMed

    Datta, Siddhartha; Samanta, Diptaman; Sinha, Priyobrata; Chakrabarti, Nilkanta

    2016-10-01

    Light at night alters behavior and cognitive performances in rodents, the variations of which in gender and stages of reproductive cycle in females are elusive. Young mice habituated in light:dark (12:12h) cycle were given a single exposure of light (100lx) at early night for one hour duration followed by experimentations in open field (closed wall with circular big arena), elevated plus maze and square habituated field for memory performance using novel object recognition task. Light effects were compared with results found during without light conditions. Proestrous females appeared to have greater locomotor activity, less anxiety and better memory performance compared to the diestrous females at night without light exposure. The status of locomotor activity, anxiety and memory performance of male mice at night without light exposure appeared to be comparable to females where the stage of estrous cycle is important to characterize the nocturnal behavior of male mice. Light maximally affected proestrous females with decrease in locomotor activity, increase in anxiety and failure of memory performance. Male and diestrous female mice performed memory performance without alteration of locomotor activity and anxiety after exposure to light where males performed better memory performance with greater locomotor activity and more anxiety compared to that of diestrous females. The present study characterizes the mice nocturnal behavior with and without a single exposure to light stimuli with its gender features and estrous cycle variation. In addition, the study indicates an association of memory performance with locomotor activity and anxiety in mice nocturnal behavior. PMID:27241632

  6. Gender features and estrous cycle variations of nocturnal behavior of mice after a single exposure to light at night.

    PubMed

    Datta, Siddhartha; Samanta, Diptaman; Sinha, Priyobrata; Chakrabarti, Nilkanta

    2016-10-01

    Light at night alters behavior and cognitive performances in rodents, the variations of which in gender and stages of reproductive cycle in females are elusive. Young mice habituated in light:dark (12:12h) cycle were given a single exposure of light (100lx) at early night for one hour duration followed by experimentations in open field (closed wall with circular big arena), elevated plus maze and square habituated field for memory performance using novel object recognition task. Light effects were compared with results found during without light conditions. Proestrous females appeared to have greater locomotor activity, less anxiety and better memory performance compared to the diestrous females at night without light exposure. The status of locomotor activity, anxiety and memory performance of male mice at night without light exposure appeared to be comparable to females where the stage of estrous cycle is important to characterize the nocturnal behavior of male mice. Light maximally affected proestrous females with decrease in locomotor activity, increase in anxiety and failure of memory performance. Male and diestrous female mice performed memory performance without alteration of locomotor activity and anxiety after exposure to light where males performed better memory performance with greater locomotor activity and more anxiety compared to that of diestrous females. The present study characterizes the mice nocturnal behavior with and without a single exposure to light stimuli with its gender features and estrous cycle variation. In addition, the study indicates an association of memory performance with locomotor activity and anxiety in mice nocturnal behavior.

  7. CEP290 alleles in mice disrupt tissue-specific cilia biogenesis and recapitulate features of syndromic ciliopathies.

    PubMed

    Rachel, Rivka A; Yamamoto, Erin A; Dewanjee, Mrinal K; May-Simera, Helen L; Sergeev, Yuri V; Hackett, Alice N; Pohida, Katherine; Munasinghe, Jeeva; Gotoh, Norimoto; Wickstead, Bill; Fariss, Robert N; Dong, Lijin; Li, Tiansen; Swaroop, Anand

    2015-07-01

    Distinct mutations in the centrosomal-cilia protein CEP290 lead to diverse clinical findings in syndromic ciliopathies. We show that CEP290 localizes to the transition zone in ciliated cells, precisely to the region of Y-linkers between central microtubules and plasma membrane. To create models of CEP290-associated ciliopathy syndromes, we generated Cep290(ko/ko) and Cep290(gt/gt) mice that produce no or a truncated CEP290 protein, respectively. Cep290(ko/ko) mice exhibit early vision loss and die from hydrocephalus. Retinal photoreceptors in Cep290(ko/ko) mice lack connecting cilia, and ciliated ventricular ependyma fails to mature. The minority of Cep290(ko/ko) mice that escape hydrocephalus demonstrate progressive kidney pathology. Cep290(gt/gt) mice die at mid-gestation, and the occasional Cep290(gt/gt) mouse that survives shows hydrocephalus and severely cystic kidneys. Partial loss of CEP290-interacting ciliopathy protein MKKS mitigates lethality and renal pathology in Cep290(gt/gt) mice. Our studies demonstrate domain-specific functions of CEP290 and provide novel therapeutic paradigms for ciliopathies. PMID:25859007

  8. Schizophrenia-like features in transgenic mice overexpressing human HO-1 in the astrocytic compartment.

    PubMed

    Song, Wei; Zukor, Hillel; Lin, Shih-Hsiung; Hascalovici, Jacob; Liberman, Adrienne; Tavitian, Ayda; Mui, Jeannie; Vali, Hojatollah; Tong, Xin-Kang; Bhardwaj, Sanjeev K; Srivastava, Lalit K; Hamel, Edith; Schipper, Hyman M

    2012-08-01

    Delineation of key molecules that act epigenetically to transduce diverse stressors into established patterns of disease would facilitate the advent of preventive and disease-modifying therapeutics for a host of neurological disorders. Herein, we demonstrate that selective overexpression of the stress protein heme oxygenase-1 (HO-1) in astrocytes of novel GFAP.HMOX1 transgenic mice results in subcortical oxidative stress and mitochondrial damage/autophagy; diminished neuronal reelin content (males); induction of Nurr1 and Pitx3 with attendant suppression of their targeting miRNAs, 145 and 133b; increased tyrosine hydroxylase and α-synuclein expression with downregulation of the targeting miR-7b of the latter; augmented dopamine and serotonin levels in basal ganglia; reduced D1 receptor binding in nucleus accumbens; axodendritic pathology and altered hippocampal cytoarchitectonics; impaired neurovascular coupling; attenuated prepulse inhibition (males); and hyperkinetic behavior. The GFAP.HMOX1 neurophenotype bears resemblances to human schizophrenia and other neurodevelopmental conditions and implicates glial HO-1 as a prime transducer of inimical (endogenous and environmental) influences on the development of monoaminergic circuitry. Containment of the glial HO-1 response to noxious stimuli at strategic points of the life cycle may afford novel opportunities for the effective management of human neurodevelopmental and neurodegenerative conditions. PMID:22875919

  9. Cocaine Hydrolase Gene Transfer Demonstrates Cardiac Safety and Efficacy against Cocaine-Induced QT Prolongation in Mice.

    PubMed

    Murthy, Vishakantha; Reyes, Santiago; Geng, Liyi; Gao, Yang; Brimijoin, Stephen

    2016-03-01

    Cocaine addiction is associated with devastating medical consequences, including cardiotoxicity and risk-conferring prolongation of the QT interval. Viral gene transfer of cocaine hydrolase engineered from butyrylcholinesterase offers therapeutic promise for treatment-seeking drug users. Although previous preclinical studies have demonstrated benefits of this strategy without signs of toxicity, the specific cardiac safety and efficacy of engineered butyrylcholinesterase viral delivery remains unknown. Here, telemetric recording of electrocardiograms from awake, unrestrained mice receiving a course of moderately large cocaine doses (30 mg/kg, twice daily for 3 weeks) revealed protection against a 2-fold prolongation of the QT interval conferred by pretreatment with cocaine hydrolase vector. By itself, this prophylactic treatment did not affect QT interval duration or cardiac structure, demonstrating that viral delivery of cocaine hydrolase has no intrinsic cardiac toxicity and, on the contrary, actively protects against cocaine-induced QT prolongation.

  10. Demonstration of pattern transfer into sub-100 nm polysilicon line/space features patterned with extreme ultraviolet lithography

    SciTech Connect

    Cardinale, G. F.; Henderson, C. C.; Goldsmith, J. E. M.; Mangat, P. J. S.; Cobb, J.; Hector, S. D.

    1999-11-01

    In two separate experiments, we have successfully demonstrated the transfer of dense- and loose-pitch line/space (L/S) photoresist features, patterned with extreme ultraviolet (EUV) lithography, into an underlying hard mask material. In both experiments, a deep-UV photoresist ({approx}90 nm thick) was spin cast in bilayer format onto a hard mask (50-90 nm thick) and was subsequently exposed to EUV radiation using a 10x reduction EUV exposure system. The EUV reticle was fabricated at Motorola (Tempe, AZ) using a subtractive process with Ta-based absorbers on Mo/Si multilayer mask blanks. In the first set of experiments, following the EUV exposures, the L/S patterns were transferred first into a SiO{sub 2} hard mask (60 nm thick) using a reactive ion etch (RIE), and then into polysilicon (350 nm thick) using a triode-coupled plasma RIE etcher at the University of California, Berkeley, microfabrication facilities. The latter etch process, which produced steep (>85 degree sign ) sidewalls, employed a HBr/Cl chemistry with a large (>10:1) etch selectivity of polysilicon to silicon dioxide. In the second set of experiments, hard mask films of SiON (50 nm thick) and SiO{sub 2} (87 nm thick) were used. A RIE was performed at Motorola using a halogen gas chemistry that resulted in a hard mask-to-photoresist etch selectivity >3:1 and sidewall profile angles {>=}85 degree sign . Line edge roughness (LER) and linewidth critical dimension (CD) measurements were performed using Sandia's GORA(c) CD digital image analysis software. Low LER values (6-9 nm, 3{sigma}, one side) and good CD linearity (better than 10%) were demonstrated for the final pattern-transferred dense polysilicon L/S features from 80 to 175 nm. In addition, pattern transfer (into polysilicon) of loose-pitch (1:2) L/S features with CDs{>=}60 nm was demonstrated. (c) 1999 American Vacuum Society.

  11. Treatment with CB2 Agonist JWH-133 Reduces Histological Features Associated with Erectile Dysfunction in Hypercholesterolemic Mice

    PubMed Central

    Fraga-Silva, Rodrigo Araujo; Costa-Fraga, Fabiana Pereira; Faye, Younouss; Savergnini, Silvia Quintao; Lenglet, Sébastien; Mach, François; Steffens, Sabine; Stergiopulos, Nikolaos; Souza dos Santos, Robson Augusto; da Silva, Rafaela Fernandes

    2013-01-01

    Hypercholesterolemia is one of the most important risk factors for erectile dysfunction, mostly due to the impairment of oxidative stress and endothelial function in the penis. The cannabinoid system might regulate peripheral mechanisms of sexual function; however, its role is still poorly understood. We investigated the effects of CB2 activation on oxidative stress and fibrosis within the corpus cavernosum of hypercholesterolemic mice. Apolipoprotein-E-knockout mice were fed with a western-type diet for 11 weeks and treated with JWH-133 (selective CB2 agonist) or vehicle during the last 3 weeks. CB2 receptor expression, total collagen content, and reactive oxygen species (ROS) production within the penis were assessed. In vitro corpus cavernosum strips preparation was performed to evaluate the nitric oxide (NO) bioavailability. CB2 protein expression was shown in cavernosal endothelial and smooth muscle cells of wild type and hypercholesterolemic mice. Treatment with JWH-133 reduced ROS production and NADPH-oxidase expression in hypercholesterolemic mice penis. Furthermore, JWH-133 increased endothelial NO synthase expression in the corpus cavernosum and augmented NO bioavailability. The decrease in oxidative stress levels was accompanied with a reduction in corpus cavernosum collagen content. In summary, CB2 activation decreased histological features, which were associated with erectile dysfunction in hypercholesterolemic mice. PMID:24302957

  12. [Specific features of the anticonvulsant effect of memantine in mice intoxicated with a model organic phosphate].

    PubMed

    Iudin, M A; Chepur, S V; Bykov, V N; Kurpiakova, A F; Subbotina, S N; Nikiforov, A S; Ivanov, I M

    2013-01-01

    The effect of memantine administration has been studied on the model of mice poisoning with an anticholinesterase compound. It is established that the memantine action is due to its influence on the cholinesterase activity in the brain, blood plasma, and erythrocytes in addition to its NMDA-blocking action. Memantine promotes oxime-induced erythrocyte enzyme reactivation on the model of mice poisoning with anticholinesterase compound (0.8 LD50).

  13. Attainment of Brown Adipocyte Features in White Adipocytes of Hormone-Sensitive Lipase Null Mice

    PubMed Central

    Ström, Kristoffer; Hansson, Ola; Lucas, Stéphanie; Nevsten, Pernilla; Fernandez, Céline; Klint, Cecilia; Movérare-Skrtic, Sofia; Sundler, Frank; Ohlsson, Claes; Holm, Cecilia

    2008-01-01

    Background Hormone-sensitive lipase (HSL) is expressed predominantly in adipose tissue, where it plays an important role in catecholamine-stimulated hydrolysis of stored tri- and diglycerides, thus mobilizing fatty acids. HSL exhibits broad substrate specificity and besides acylglycerides it hydrolyzes cholesteryl esters, retinyl esters and lipoidal esters. Despite its role in fatty acid mobilization, HSL null mice have been shown to be resistant to diet-induced obesity. Methodology/Principal Findings Following a high-fat diet (HFD) regimen, energy expenditure, measured using indirect calorimetry, was increased in HSL null mice. White adipose tissue of HSL null mice was characterized by reduced mass and reduced protein expression of PPARγ, a key transcription factor in adipogenesis, and stearoyl-CoA desaturase 1, the expression of which is known to be positively correlated to the differentiation state of the adipocyte. The protein expression of uncoupling protein-1 (UCP-1), the highly specific marker of brown adipocytes, was increased 7-fold in white adipose tissue of HSL null mice compared to wildtype littermates. Transmission electron microscopy revealed an increase in the size of mitochondria of white adipocytes of HSL null mice. The mRNA expression of pRb and RIP140 was decreased in isolated white adipocytes, while the expression of UCP-1 and CPT1 was increased in HSL null mice compared to wildtype littermates. Basal oxygen consumption was increased almost 3-fold in white adipose tissue of HSL null mice and was accompanied by increased uncoupling activity. Conclusions These data suggest that HSL is involved in the determination of white versus brown adipocytes during adipocyte differentiation The exact mechanism(s) underlying this novel role of HSL remains to be elucidated, but it seems clear that HSL is required to sustain normal expression levels of pRb and RIP140, which both promote differentiation into the white, rather than the brown, adipocyte lineage

  14. Targeted disruption of the Hexa gene results in mice with biochemical and pathologic features of Tay-Sachs disease.

    PubMed

    Yamanaka, S; Johnson, M D; Grinberg, A; Westphal, H; Crawley, J N; Taniike, M; Suzuki, K; Proia, R L

    1994-10-11

    Tay-Sachs disease, the prototype of the GM2 gangliosidoses, is a catastrophic neurodegenerative disorder of infancy. The disease is caused by mutations in the HEXA gene resulting in an absence of the lysosomal enzyme, beta-hexosaminidase A. As a consequence of the enzyme deficiency, GM2 ganglioside accumulates progressively, beginning early in fetal life, to excessive amounts in the central nervous system. Rapid mental and motor deterioration starting in the first year of life leads to death by 2-4 years of age. Through the targeted disruption of the mouse Hexa gene in embryonic stem cells, we have produced mice with biochemical and neuropathologic features of Tay-Sachs disease. The mutant mice displayed < 1% of normal beta-hexosaminidase A activity and accumulated GM2 ganglioside in their central nervous system in an age-dependent manner. The accumulated ganglioside was stored in neurons as membranous cytoplasmic bodies characteristically found in the neurons of Tay-Sachs disease patients. At 3-5 months of age, the mutant mice showed no apparent defects in motor or memory function. These beta-hexosaminidase A-deficient mice should be useful for devising strategies to introduce functional enzyme and genes into the central nervous system. This model may also be valuable for studying the biochemical and pathologic changes occurring during the course of the disease.

  15. Targeted disruption of the Hexa gene results in mice with biochemical and pathologic features of Tay-Sachs disease

    SciTech Connect

    Proia, R.L.; Yamanaka, S.; Johnson, M.D.

    1994-09-01

    Tay-Sachs disease, the prototype of the G{sub M2} gangliosidoses, is a catastrophic neurodegenerative disorder of infancy. The disease is caused by mutations in the HEXA gene resulting in an absence of the lysosomal enzyme, {beta}-hexosaminidase A. As consequence of the enzyme deficiency, G{sub M2} ganglioside accumulates progressively, beginning early in fetal life, to excessive amounts in the central nervous system (CNS). Rapid mental and motor deterioration starting in the first year of life leads to death by 2 to 4 years of age. Through the targeted disruption of the Hexa gene in embryonic stem cells, we have produced mice with biochemical and neuropathologic features of Tay-Sachs disease. The mutant mice exhibited less than 1% of normal {beta}-hexosaminidase A activity and accumulated G{sub M2} ganglioside in their CNS in an age-dependent manner. The accumulated ganglioside was stored in neurons as membranous cytoplasmic bodies characteristically found in the neurons of Tay-Sachs disease patients. At three to five months of age the mutant mice showed no apparent defects in motor or memory function. These {beta}-hexosaminidase A deficient mice should be useful for devising strategies to introduce functional enzymes and genes into the CNS. This model may also be valuable for studying the biochemical and pathologic changes occurring during the course of the disease.

  16. Tau Protein Mediates APP Intracellular Domain (AICD)-Induced Alzheimer’s-Like Pathological Features in Mice

    PubMed Central

    Dawson, Hana N.; Pimplikar, Sanjay W.

    2016-01-01

    Amyloid precursor protein (APP) is cleaved by gamma-secretase to simultaneously generate amyloid beta (Aβ) and APP Intracellular Domain (AICD) peptides. Aβ plays a pivotal role in Alzheimer’s disease (AD) pathogenesis but recent studies suggest that amyloid-independent mechanisms also contribute to the disease. We previously showed that AICD transgenic mice (AICD-Tg) exhibit AD-like features such as tau pathology, aberrant neuronal activity, memory deficits and neurodegeneration in an age-dependent manner. Since AD is a tauopathy and tau has been shown to mediate Aβ–induced toxicity, we examined the role of tau in AICD-induced pathological features. We report that ablating endogenous tau protects AICD-Tg mice from deficits in adult neurogenesis, seizure severity, short-term memory deficits and neurodegeneration. Deletion of tau restored abnormal phosphorylation of NMDA receptors, which is likely to underlie hyperexcitability and associated excitotoxicity in AICD-Tg mice. Conversely, overexpression of wild-type human tau aggravated receptor phosphorylation, impaired adult neurogenesis, memory deficits and neurodegeneration. Our findings show that tau is essential for mediating the deleterious effects of AICD. Since tau also mediates Aβ-induced toxic effects, our findings suggest that tau is a common downstream factor in both amyloid-dependent and–independent pathogenic mechanisms and therefore could be a more effective drug target for therapeutic intervention in AD. PMID:27459671

  17. Physiological Features of Perigonadal Adipose Tissue Containing Uncoupling Protein UCP1 in ICR Mice.

    PubMed

    Elsukova, E I; Medvedev, L N; Mizonova, O V

    2016-07-01

    Immunoreactive uncoupling protein UCP1 was found in the perigonadal fat of only twothirds of 14-week-old male ICR mice. The presence of UCP1 had no effect on the rate of O2 consumption by the adipose tissue. The cellularity of perigonadal fat estimated by the DNA content was significantly higher in tissue containing UCP1 than in samples without this protein. This regularity was also observed after adaptation of mice to moderate cold (10oC) over 8 weeks. PMID:27496031

  18. Inhibition of myostatin does not ameliorate disease features of severe spinal muscular atrophy mice

    PubMed Central

    Sumner, Charlotte J.; Wee, Claribel D.; Warsing, Leigh C.; Choe, Dong W.; Ng, Andrew S.; Lutz, Cathleen; Wagner, Kathryn R.

    2009-01-01

    There is currently no treatment for the inherited motor neuron disease, spinal muscular atrophy (SMA). Severe SMA causes lower motor neuron loss, impaired myofiber development, profound muscle weakness and early mortality. Myostatin is a transforming growth factor-β family member that inhibits muscle growth. Loss or blockade of myostatin signaling increases muscle mass and improves muscle strength in mouse models of primary muscle disease and in the motor neuron disease, amyotrophic lateral sclerosis. In this study, we evaluated the effects of blocking myostatin signaling in severe SMA mice (hSMN2/delta7SMN/mSmn−/−) by two independent strategies: (i) transgenic overexpression of the myostatin inhibitor follistatin and (ii) post-natal administration of a soluble activin receptor IIB (ActRIIB-Fc). SMA mice overexpressing follistatin showed little increase in muscle mass and no improvement in motor function or survival. SMA mice treated with ActRIIB-Fc showed minimal improvement in motor function, and no extension of survival compared with vehicle-treated mice. Together these results suggest that inhibition of myostatin may not be a promising therapeutic strategy in severe forms of SMA. PMID:19477958

  19. Heterozygous Pitx2 Null Mice Accurately Recapitulate the Ocular Features of Axenfeld-Rieger Syndrome and Congenital Glaucoma

    PubMed Central

    Chen, Lisheng; Gage, Philip J.

    2016-01-01

    Purpose The purpose of this analysis was to assess the utility of Pitx2+/− mice as a model for the ocular features of Axenfeld-Rieger Syndrome and for congenital glaucoma. Methods Eyes of Pitx2+/− and wild-type littermates were examined clinically using optical coherence tomography (OCT) and fundus photography. Intraocular pressures were measured using a TonoLab rebound tonometer. Eyes were examined histologically to assess PITX2 expression, structural integrity, and optic nerve and ganglion cell content. Results PITX2 is present postnatally in the corneal endothelium and stroma, iris stroma, trabecular meshwork, and Schlemm's canal. Reduced central corneal thickness, iris defects, and iridicorneal adhesions are all prevalent in Pitx2+/− eyes. Although optic nerve heads appear normal at postnatal day 7, IOP is elevated and optic nerve head cupping is fully penetrant in Pitx2+/− eyes by 3 weeks of age. Neurodegeneration is present in a significant percentage of optic nerves from Pitx2+/− mice by 3 weeks of age, and is fully penetrant by 2 months of age. Pitx2+/− eyes show significant reductions in specifically ganglion cell density in all four quadrants by 2 months of age. Conclusions Pitx2+/− mice model the major ocular features of Axenfeld-Rieger Syndrome and will be an important resource for understanding the molecular mechanisms leading to anterior segment dysgenesis and a high prevalence of glaucoma in this disease. In addition, these mice may provide an efficient new model for assessing the molecular events in glaucoma more generally, and for developing and testing new treatment paradigms for this disease. PMID:27654429

  20. Expansion of natural killer cells in mice transgenic for IgM antibody to ganglioside GD2: demonstration of prolonged survival after challenge with syngeneic tumor cells.

    PubMed

    Kawashima, Ikuo; Yoshida, Yukiko; Taya, Chouji; Shitara, Hiroshi; Yonekawa, Hiromichi; Karasuyama, Hajime; Tada, Nobuhiko; Furukawa, Koichi; Tai, Tadashi

    2003-08-01

    IgM antibodies to gangliosides, sialic acid-containing glycosphingolipids, have been shown to mediate anti-tumor effects in cancer patients with melanoma and neuroblastoma and to correlate with survival. Mechanisms by which the antibodies induce tumor suppression, however, have not been systematically studied. To investigate this point, we produced and characterized C57BL/6 mice transgenic for IgM antibody to ganglioside GD2. The transgenic (TG) mice showed high IgM, but not IgG antibody titers against GD2 in their sera. No significant clinical symptoms were observed. When EL4 cells, syngeneic T lymphoma that express ganglioside GD2, were injected into TG mice, prolonged survival was observed. Complement-dependent cytotoxicity (CDC) of EL4 cells was mediated with TG mice sera. Neither antibody-dependent cellular cytotoxicity with their sera nor cytotoxic T lymphocyte activity to EL4 cells was shown in TG mice. Spleen lymphocytes from TG mice had increased numbers of natural killer (NK) cells, but not T cells, B cells, or macrophages compared with wild-type mice. Depletion of NK cells with anti-asialo GM1 rabbit serum reduced or abrogated the observed anti-tumor effects, suggesting that NK cells play a major role in tumor eradication or suppression. NK cell activity in TG mice was much higher than wild-type mice. Moreover, TG mice showed prolonged survival after injection with syngeneic B16 melanoma cells, which express GM3, but not GD2 or GD3. Taking these results together, our studies demonstrate that the TG mice have significant anti-tumor characteristics, probably due to CDC and NK cell expansion and activation with anti-ganglioside GD2 antibody.

  1. Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur

    SciTech Connect

    Klebig, M.L.; Woychik, R.P.; Wilkinson, J.E.; Geisler, J.G. |

    1995-05-23

    Mice that carry the lethal yellow (A{sup y}) or viable yellow (A{sup vy}) mutation, two dominant mutations of the agouti (a) gene in mouse chromosome 2, exhibit a phenotype that includes yellow fur, marked obesity, a form of type II diabetes associated with insulin resistance, and an increased susceptibility to tumor development. Molecular analyses of these and several other dominant {open_quotes}obese yellow{close_quotes} a-locus mutations suggested that ectopic expression of the normal agouti protein gives rise to this complex pleiotropic phenotype. We have now tested this hypothesis directly by generating transgenic mice that ectopically express an agouti cDNA clone encoding the normal agouti protein in all tissues examined. Transgenic mice of both sexes have yellow fur, become obese, and develop hyperinsulinemia. In addition, male transgenic mice develop hyperglycemia by 12-20 weeks of age. These results demonstrate conclusively that the ectopic agouti expression is responsible for most, if not all, of the phenotypic traits of the dominant, obese yellow mutants. 42 refs., 5 figs.

  2. Experimental hepatic fibrosis due to Capillaria hepatica infection (differential features presented by rats and mice).

    PubMed

    Andrade, Stelamares Boyda de; Andrade, Zilton A

    2004-06-01

    Rats and mice are among the most susceptible hosts for the helminth Capillaria hepatica. More information on the similarities and differences between the hepatic pathology presented by these two parasite hosts are needed, since they may represent good models for the study of hepatic fibrosis. Early changes are similar for both hosts and are represented by necro-inflammatory lesions around dead parasites and their eggs and diffuse and intense reactive hepatitis. Although worms remain alive longer in mice than in rats, hepatic changes are more rapidly and deeply modulated in the former, even leading to almost complete disappearance of fibrosis. As for the rats, the modulation of the focal lesions is followed by the formation of septal fibrosis, a process where fine and long fibrous septa appear connecting portal spaces and central veins in such a way as to form a final morphologic picture of cirrhosis. Hepatic functional changes usually present good correlations with the morphologic findings at the different phases of the infection evolution. Therefore C. hepatica infection in rats and mice represent two different models of hepatic fibrosis and these differences, if properly known and understood, can be explored to answer different questions regarding several aspects of hepatic fibrosis.

  3. CXC receptor knockout mice: characterization of skeletal features and membranous bone healing in the adult mouse.

    PubMed

    Bischoff, David S; Sakamoto, Taylor; Ishida, Kenji; Makhijani, Nalini S; Gruber, Helen E; Yamaguchi, Dean T

    2011-02-01

    The potential role of CXC chemokines bearing the glu-leu-arg (ELR) motif in bone repair was studied using a cranial defect (CD) model in mice lacking the CXC receptor (mCXCR(-/-) knockout mice), which is homologous to knockout of the human CXC receptor 2 (CXCR2) gene. During the inflammatory stage of bone repair, ELR CXC chemokines are released by inflammatory cells and serve as chemotactic and angiogenic factors. mCXCR(-/-) mice were smaller in weight and length from base of tail to nose tip, compared to WT littermates. DEXA analysis indicated that bone mineral density (BMD), bone mineral content (BMC), total area (TA), bone area (BA), and total tissue mass (TTM) were decreased in the mCXCR(-/-) mice at 6, 12, and 18 weeks of age. Trabecular bone characteristics in mCXCR(-/-) (% bone, connectivity, number, and thickness) were reduced, and trabecular spacing was increased as evidenced by μCT. There was no difference in bone formation or resorption indices measured by bone histomorphometry. Trabecular BMD was not altered. Cortical bone volume, BMD, and thickness were reduced; whereas, bone marrow volume was increased in mCXCR(-/-). Decreased polar moment of inertia (J) in the tibias/femurs suggested that the mCXCR(-/-) long bones are weaker. This was confirmed by three-point bending testing of the femurs. CDs created in 6-week-old male mCXCR(-/-) and WT littermates were not completely healed at 12 weeks; WT animals, however, had significantly more bone in-growth than mCXCR(-/-). New bone sites were identified using polarized light and assessed for numbers of osteocyte (OCy) lacunae and blood vessels (BlV) around the original CD. In new bone, the number of BlV in WT was >2× that seen in mCXCR(-/-). Bone histomorphometry parameters in the cranial defect did not show any difference in bone formation or resorption markers. In summary, studies showed that mCXCR(-/-) mice have (1) reduced weight and size; (2) decreased BMD and BMC; (3) decreased amounts of trabecular

  4. Some mice feature 5th pharyngeal arch arteries and double-lumen aortic arch malformations.

    PubMed

    Geyer, Stefan H; Weninger, Wolfgang J

    2012-01-01

    A 5th pair of pharyngeal arch arteries (PAAs) has never been identified with certainty in mice. Murines in general are considered to not develop a 5th pair. If true, the significance of the mouse as a model for researching the genesis of malformations of the great intrathoracic arteries is limited. We aimed to investigate whether mouse embryos develop a 5th pair of PAAs and to identify malformations known to be caused by defective remodelling of the 5th PAAs. We employed the high-resolution episcopic microscopy method for creating digital volume data and three-dimensional (3D) computer models of the great intrathoracic arteries of 30 mouse embryos from days 12-12.5 post conception and 180 mouse fetuses from days 14.5 and 15.5 post conception. The 3D models of the fetuses were screened for the presence of a double-lumen aortic arch malformation. We identified such a malformation in 1 fetus. The 3D models of the embryos were analysed for the presence of 5th PAAs. Six of the 30 embryos (20%) showed a 5th PAA bilaterally, and an additional 9 (30%) showed a 5th PAA unilaterally. Our results prove that some mice do develop a 5th pair of PAAs. They also show that malformations which occur rarely in humans and result from defective remodelling of the left 5th PAA can be identified in mice as well. Thus, the mouse does represent an excellent model for researching the mechanisms driving PAA remodelling and the genesis of malformations of the great intrathoracic arteries.

  5. Low doses of mercuric chloride cause the main features of anti-nucleolar autoimmunity in female outbred CFW mice.

    PubMed

    Arefieva, Alla S; Kamaeva, Alfia G; Krasilshchikova, Marina S

    2016-09-01

    The growth of the influence of anthropogenic factors aimed on the improvement of human life has its side effect, for example, living organisms receive increasing exposure to toxic mercuric compounds. Experimental data show that mercury (Hg) salts are able to induce systemic autoimmunity in rodents. This Hg-induced autoimmune process (HgIA) is characterized by T cell-dependent polyclonal activation of B lymphocytes, increased level of serum immunoglobulin G1 (IgG1) and immunoglobulin E (IgE), production of antinucleolar autoantibodies (ANoA), and immune complex deposition in multiple organs. HgIA in mice is used as a model of human systemic autoimmune disorders. However, the dose of mercuric chloride (HgCl2) usually used in laboratory mice to induce HgIA is above the allowable limit for everyday levels of Hg exposure in humans. So, we decided to determine the lowest dose of HgCl2 that is able to trigger autoimmunity in outbred Carworth Farms Swiss Webster (CFW) mice not genetically prone to HgIA development. The lowest dose (50 µg/kg body weight (b.w.)/week) was chosen to match the World Health Organization provisional weekly tolerable intake of total Hg for humans. We also tested HgCl2 at 500 and 1500 µg/kg b.w./week (6.5- and 2-fold less than usually used for induction of HgIA in mice). We found that even the lowest dose of Hg resulted in a statistically significant increase in serum level of IgG1 after 8 weeks of treatment. HgCl2 in doses 500 and 1500 µg/kg b.w./week resulted in a significant increase in serum level of IgG1 after 4 weeks of treatment, followed by ANoA production. Sera of HgCl2-treated mice stained the regions in which the major autoantigen in HgIA, fibrillarin, was revealed. These results suggest that low doses of Hg are able to induce the main features of HgIA in genetically heterozygous mice, and that humans chronically exposed to low doses of Hg may be at risk of autoimmunity induction regardless of their genetic background.

  6. α2-Null mutant mice have altered levels of neuronal activity in restricted midbrain and limbic brain regions during nicotine withdrawal as demonstrated by cfos expression.

    PubMed

    Upton, Montana; Lotfipour, Shahrdad

    2015-10-15

    Neuronal nicotinic acetylcholine receptors (nAChRs) are the primary binding sites for nicotine within the brain. Using alpha(α)2 nAChR subunit-null mutant mice, the current study evaluates whether the absence of this gene product during mecamylamine-precipitated nicotine withdrawal eliminates neuronal activity within selective midbrain and limbic brain regions, as determined by the expression of the immediate early gene, cfos. Our results demonstrate that nicotine withdrawal enhances neuronal activity within the interpeduncular nucleus and dorsal hippocampus, which is absent in mice null for α2-containing nAChRs. In contrast, we observe that α2-null mutant mice exhibit a suppression of neuronal activity in the dentate gyrus in mice undergoing nicotine withdrawal. Interestingly, α2-null mutant mice display potentiated neuronal activity specifically within the stratum lacunosum moleculare layer of the hippocampus, independent of nicotine withdrawal. Overall, our findings demonstrate that α2-null mutant mice have altered cfos expression in distinct populations of neurons within selective midbrain and limbic brain structures that mediate baseline and nicotine withdrawal-induced neuronal activity.

  7. Huntingtons Disease Mice Infected with Toxoplasma gondii Demonstrate Early Kynurenine Pathway Activation, Altered CD8+ T-Cell Responses, and Premature Mortality

    PubMed Central

    Donley, David W.; Olson, Andrew R.; Raisbeck, Merl F.; Fox, Jonathan H.; Gigley, Jason P.

    2016-01-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a polyglutamine-repeat expansion in the huntingtin protein. Activation of the kynurenine pathway of tryptophan degradation is implicated in the pathogenesis of HD. Indoleamine-2,3-dioxygenase (IDO) catalyzes the oxidation of tryptophan to kynurenine, the first step in this pathway. The prevalent, neuroinvasive protozoal pathogen Toxoplasma gondii (T. gondii) results in clinically silent life-long infection in immune-competent individuals. T. gondii infection results in activation of IDO which provides some protection against the parasite by depleting tryptophan which the parasite cannot synthesize. The kynurenine pathway may therefore represent a point of synergism between HD and T. gondii infection. We show here that IDO activity is elevated at least four-fold in frontal cortex and striata of non-infected N171-82Q HD mice at 14-weeks corresponding to early–advanced HD. T. gondii infection at 5 weeks resulted in elevation of cortical IDO activity in HD mice. HD-infected mice died significantly earlier than wild-type infected and HD control mice. Prior to death, infected HD mice demonstrated decreased CD8+ T-lymphocyte proliferation in brain and spleen compared to wild-type infected mice. We demonstrate for the first time that HD mice have an altered response to an infectious agent that is characterized by premature mortality, altered immune responses and early activation of IDO. Findings are relevant to understanding how T. gondii infection may interact with pathways mediating neurodegeneration in HD. PMID:27611938

  8. Huntingtons Disease Mice Infected with Toxoplasma gondii Demonstrate Early Kynurenine Pathway Activation, Altered CD8+ T-Cell Responses, and Premature Mortality.

    PubMed

    Donley, David W; Olson, Andrew R; Raisbeck, Merl F; Fox, Jonathan H; Gigley, Jason P

    2016-01-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a polyglutamine-repeat expansion in the huntingtin protein. Activation of the kynurenine pathway of tryptophan degradation is implicated in the pathogenesis of HD. Indoleamine-2,3-dioxygenase (IDO) catalyzes the oxidation of tryptophan to kynurenine, the first step in this pathway. The prevalent, neuroinvasive protozoal pathogen Toxoplasma gondii (T. gondii) results in clinically silent life-long infection in immune-competent individuals. T. gondii infection results in activation of IDO which provides some protection against the parasite by depleting tryptophan which the parasite cannot synthesize. The kynurenine pathway may therefore represent a point of synergism between HD and T. gondii infection. We show here that IDO activity is elevated at least four-fold in frontal cortex and striata of non-infected N171-82Q HD mice at 14-weeks corresponding to early-advanced HD. T. gondii infection at 5 weeks resulted in elevation of cortical IDO activity in HD mice. HD-infected mice died significantly earlier than wild-type infected and HD control mice. Prior to death, infected HD mice demonstrated decreased CD8+ T-lymphocyte proliferation in brain and spleen compared to wild-type infected mice. We demonstrate for the first time that HD mice have an altered response to an infectious agent that is characterized by premature mortality, altered immune responses and early activation of IDO. Findings are relevant to understanding how T. gondii infection may interact with pathways mediating neurodegeneration in HD. PMID:27611938

  9. A diet rich in OMEGA-6 polyunsaturated fat and sucrose reproduces key features of metabolic syndrome in C57BL/6 mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine whether a diet enriched in v-6 fatty acids and sucrose will reproduce features of metabolic syndrome in C57BL/6 mice. 4- to 7-week-old male C57BL/6 mice were randomized to chow (13% kcal fat, lard and corn oil) or high fat/high sucrose (HF/HS) diet (48% kcal fat, corn oil) for a period ...

  10. Haplosufficient genomic androgen receptor signaling is adequate to protect female mice from induction of polycystic ovary syndrome features by prenatal hyperandrogenization.

    PubMed

    Caldwell, A S L; Eid, S; Kay, C R; Jimenez, M; McMahon, A C; Desai, R; Allan, C M; Smith, J T; Handelsman, D J; Walters, Kirsty A

    2015-04-01

    Polycystic ovary syndrome (PCOS) is associated with reproductive, endocrine, and metabolic abnormalities. Because hyperandrogenism is the most consistent PCOS feature, we used wild-type (WT) and androgen receptor (AR) knockout (ARKO) mice, together with a mouse model of PCOS, to investigate the contribution of genomic AR-mediated actions in the development of PCOS traits. PCOS features were induced by prenatal exposure to dihydrotestosterone (250 μg) or oil vehicle (control) on days 16-18 of gestation in WT, heterozygote, and homozygote ARKO mice. DHT treatment of WT mice induced ovarian cysts (100% vs 0%), disrupted estrous cycles (42% vs 100% cycling), and led to fewer corpora lutea (5.0±0.4 vs 9.8±1.8). However, diestrus serum LH and FSH, and estradiol-induced-negative feedback as well as hypothalamic expression of kisspeptin, neurokinin B, and dynorphin, were unaffected by DHT treatment in WT mice. DHT-treated WT mice exhibited a more than 48% increase in adipocyte area but without changes in body fat. In contrast, heterozygous and homozygous ARKO mice exposed to DHT maintained comparable ovarian (histo)morphology, estrous cycling, and corpora lutea numbers, without any increase in adipocyte size. These findings provide strong evidence that genomic AR signaling is an important mediator in the development of these PCOS traits with a dose dependency that allows even AR haplosufficiency to prevent induction by prenatal androgenization of PCOS features in adult life.

  11. Boron neutron capture therapy demonstrated in mice bearing EMT6 tumors following selective delivery of boron by rationally designed liposomes

    PubMed Central

    Kueffer, Peter J.; Maitz, Charles A.; Khan, Aslam A.; Schuster, Seth A.; Shlyakhtina, Natalia I.; Jalisatgi, Satish S.; Brockman, John D.; Nigg, David W.; Hawthorne, M. Frederick

    2013-01-01

    The application of boron neutron capture therapy (BNCT) following liposomal delivery of a 10B-enriched polyhedral borane and a carborane against mouse mammary adenocarcinoma solid tumors was investigated. Unilamellar liposomes with a mean diameter of 134 nm or less, composed of an equimolar mixture of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine and incorporating Na3[1-(2′-B10H9)-2-NH3B10H8] in the aqueous interior and K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer, were injected into the tail veins of female BALB/c mice bearing right flank EMT6 tumors. Biodistribution studies indicated that two identical injections given 24 h apart resulted in tumor boron levels exceeding 67 µg/g tumor at 54 h—with tumor/blood boron ratios being greatest at 96 h (5.68:1; 43 µg boron/g tumor)—following the initial injection. For BNCT experiments, tumor-bearing mice were irradiated 54 h after the initial injection for 30 min with thermal neutrons, resulting in a total fluence of 1.6 × 1012 neutrons per cm2 (±7%). Significant suppression of tumor growth was observed in mice given BNCT vs. control mice (only 424% increase in tumor volume at 14 d post irradiation vs. 1551% in untreated controls). In a separate experiment in which mice were given a second injection/irradiation treatment 7 d after the first, the tumor growth was vastly diminished (186% tumor volume increase at 14 d). A similar response was obtained for mice irradiated for 60 min (169% increase at 14 d), suggesting that neutron fluence was the limiting factor controlling BNCT efficacy in this study. PMID:23536304

  12. An Intradermal Inoculation Model of Scrub Typhus in Swiss CD-1 Mice Demonstrates More Rapid Dissemination of Virulent Strains of Orientia tsutsugamushi

    PubMed Central

    Sunyakumthorn, Piyanate; Paris, Daniel H.; Chan, Teik-Chye; Jones, Margaret; Luce-Fedrow, Alison; Chattopadhyay, Suchismita; Jiang, Ju; Anantatat, Tippawan; Turner, Gareth D. H.; Day, Nicholas P. J.; Richards, Allen L.

    2013-01-01

    Scrub typhus is an important endemic disease of the Asia-Pacific region caused by Orientia tsutsugamushi. To develop an effective vaccine to prevent scrub typhus infection, a better understanding of the initial host-pathogen interaction is needed. The objective of this study was to investigate early bacterial dissemination in a CD-1 Swiss outbred mouse model after intradermal injection of O. tsutsugamushi. Three human pathogenic strains of O. tsutsugamushi (Karp, Gilliam, and Woods) were chosen to investigate the early infection characteristics associated with bacterial virulence. Tissue biopsies of the intradermal injection site and draining lymph nodes were examined using histology and immunohistochemistry to characterize bacterial dissemination, and correlated with quantitative real-time PCR for O. tsutsugamushi in blood and tissue from major organs. Soluble adhesion molecules were measured to examine cellular activation in response to infection. No eschar formation was seen at the inoculation site and no clinical disease developed within the 7 day period of observation. However, O. tsutsugamushi was localized at the injection site and in the draining lymph nodes by day 7 post inoculation. Evidence of leukocyte and endothelial activation was present by day 7 with significantly raised levels of sL-selectin, sICAM-1 and sVCAM-1. Infection with the Karp strain was associated with earlier and higher bacterial loads and more extensive dissemination in various tissues than the less pathogenic Gilliam and Woods strains. The bacterial loads of O. tsutsugamushi were highest in the lungs and spleens of mice inoculated with Karp and Gilliam, but not Woods strains. Strains of higher virulence resulted in more rapid systemic infection and dissemination in this model. The CD-1 mouse intradermal inoculation model demonstrates features relevant to early scrub typhus infection in humans, including the development of regional lymphadenopathy, leukocyte activation and distant

  13. Pituitary and ovarian abnormalities demonstrated by CT and ultrasound in children with features of the McCune-Albright syndrome

    SciTech Connect

    Rieth, K.G.; Comite, F.; Shawker, T.H.; Cutler, G.B. Jr.

    1984-11-01

    In a random series of 97 children referred to the National Institutes of Health with a presumptive diagnosis of precocious puberty, eight girls were found to have features of the McCune-Albright syndrome, including fibrous dysplasia of bone and/or skin lesions resembling cafe au lait spots. Radiographic evaluation of these patients included computed tomography of the head and pelvic ultrasound. The pituitary glands were suspicious for abnormality in five of the eight girls. Seven girls underwent pelvic ultrasound, and in all of them the ovaries were considered to be abnormal for their chronological age; in addition, two had functional ovarian cysts. The role of diagnostic radiological studies in the diagnosis of this syndrome is discussed.

  14. Design and operating features of the high-level waste vitrification system for the West Valley demonstration project

    SciTech Connect

    Siemens, D.H.; Beary, M.M.; Barnes, S.M.; Berger, D.N.; Brouns, R.A.; Chapman, C.C.; Jones, R.M.; Peters, R.D.; Peterson, M.E.

    1986-03-01

    A liquid-fed joule-heated ceramic melter system is the reference process for immobilization of the high-level liquid waste in the US and several foreign countries. This system has been under development for over ten years at Pacific Northwest Laboratory and other national laboratories operated for the US Department of Energy. Pacific Northwest Laboratory contributed to this research through its Nuclear Waste Treatment Program and used applicable data to design and test melters and related systems using remote handling of simulated radioactive wastes. This report describes the equipment designed in support of the high-level waste vitrification program at West Valley, New York. Pacific Northwest Laboratory worked closely with West Valley Nuclear Services Company to design a liquid-fed ceramic melter, a liquid waste preparation and feed tank and pump, an off-gas treatment scrubber, and an enclosed turntable for positioning the waste canisters. Details of these designs are presented including the rationale for the design features and the alternatives considered.

  15. Demonstration of motionless Knudsen pump based micro-gas chromatography featuring micro-fabricated columns and on-column detectors.

    PubMed

    Liu, Jing; Gupta, Naveen K; Wise, Kensall D; Gianchandani, Yogesh B; Fan, Xudong

    2011-10-21

    This paper reports the investigation of a micro-gas chromatography (μGC) system that utilizes an array of miniaturized motionless Knudsen pumps (KPs) as well as microfabricated separation columns and optical detectors. A prototype system was built to achieve a flow rate of 1 mL min(-1) and 0.26 mL min(-1) for helium and dry air, respectively, when they were used as carrier gas. This system was then employed to evaluate GC performance compromises and demonstrate the ability to separate and detect gas mixtures containing analytes of different volatilities and polarities. Furthermore, the use of pressure programming of the KP array was demonstrated to significantly shorten the analysis time while maintaining a high detection resolution. Using this method, we obtained a high resolution detection of 5 alkanes of different volatilities within 5 min. Finally, we successfully detected gas mixtures of various polarities using a tandem-column μGC configuration by installing two on-column optical detectors to obtain complementary chromatograms.

  16. Collagen induced arthritis (CIA) in mice features regulatory transcriptional network connecting major histocompatibility complex (MHC H2) with autoantigen genes in the thymus.

    PubMed

    Donate, Paula B; Fornari, Thaís A; Junta, Cristina M; Magalhães, Danielle A; Macedo, Cláudia; Cunha, Thiago M; Nguyen, Catherine; Cunha, Fernando Q; Passos, Geraldo A

    2011-05-01

    Considering that imbalance of central tolerance in the thymus contributes to aggressive autoimmunity, we compared the expression of peripheral tissue autoantigens (PTA) genes, which are involved in self-representation in the thymic stroma, of two mouse strains; DBA-1/J (MHC-H2(q)) susceptible and DBA-2/J (MHC-H2(d)) resistant to collagen induced arthritis (CIA). We evaluate whether these strains differ in their thymic gene expression, allowing identification of genes that might play a role in susceptibility/resistance to CIA. Microarray profiling showed that 1093 PTA genes were differentially modulated between collagen immunized DBA-1/J and DBA-2/J mice. These genes were assigned to 17 different tissues/organs, including joints/bone, characterizing the promiscuous gene expression (PGE), which is implicated in self-representation. Hierarchical clustering of microarray data and quantitative RT-PCR analysis showed that Aire (autoimmune regulator), an important regulator of the PGE process, Aire-dependent (insulin), Aire-independent (Col2A1 and Gad67), and other 22 joint/bone autoantigen genes were down-regulated in DBA-1/J compared with DBA-2/J in the thymus. Considering the importance of MHC-H2 in peptide-self presentation and autoimmunity susceptibility, we reconstructed transcriptional networks of both strains based on actual microarray data. The networks clearly demonstrated different MHC-H2 transcriptional interactions with PTAs genes. DBA-1/J strain featured MHC-H2 as a node influencing downstream genes. Differently, in DBA-2/J strain network MHC-H2 was exclusively self-regulated and does not control other genes. These findings provide evidence that CIA susceptibility in mice may be a reflex of a cascade-like transcriptional control connecting different genes to MHC-H2 in the thymus.

  17. Plasma biomarkers of liver injury and inflammation demonstrate a lack of apoptosis during obstructive cholestasis in mice

    SciTech Connect

    Woolbright, Benjamin L.; Antoine, Daniel J.; Jenkins, Rosalind E.; Bajt, Mary Lynn; Park, B. Kevin; Jaeschke, Hartmut

    2013-12-15

    Cholestasis is a pathological common component of numerous liver diseases that results in hepatotoxicity, inflammation, and cirrhosis when untreated. While the predominant hypothesis in cholestatic liver injury remains hepatocyte apoptosis due to direct toxicity of hydrophobic bile acid exposure, recent work suggests that the injury occurs through inflammatory necrosis. In order to resolve this controversy, we used novel plasma biomarkers to assess the mechanisms of cell death during early cholestatic liver injury. C57Bl/6 mice underwent bile duct ligation (BDL) for 6–72 h, or sham operation. Another group of mice were given D-galactosamine and endotoxin as a positive control for apoptosis and inflammatory necrosis. Plasma levels of full length cytokeratin-18 (FL-K18), microRNA-122 (miR-122) and high mobility group box-1 protein (HMGB1) increased progressively after BDL with peak levels observed after 48 h. These results indicate extensive cell necrosis after BDL, which is supported by the time course of plasma alanine aminotransferase activities and histology. In contrast, plasma caspase-3 activity, cleaved caspase-3 protein and caspase-cleaved cytokeratin-18 fragments (cK18) were not elevated at any time during BDL suggesting the absence of apoptosis. In contrast, all plasma biomarkers of necrosis and apoptosis were elevated 6 h after Gal/End treatment. In addition, acetylated HMGB1, a marker for macrophage and monocyte activation, was increased as early as 12 h but mainly at 48–72 h. However, progressive neutrophil accumulation in the area of necrosis started at 6 h after BDL. In conclusion, these data indicate that early cholestatic liver injury in mice is an inflammatory event, and occurs through necrosis with little evidence for apoptosis. - Highlights: • The mechanism of cell death during cholestasis remains a controversial topic. • Plasma biomarkers offer new insight into cell death after bile duct ligation. • Cytokeratin-18, microRNA-122 and HMGB

  18. Subchronic and mild social defeat stress accelerates food intake and body weight gain with polydipsia-like features in mice.

    PubMed

    Goto, Tatsuhiko; Kubota, Yoshifumi; Tanaka, Yuki; Iio, Wataru; Moriya, Naoko; Toyoda, Atsushi

    2014-08-15

    Development and characterization of animal models of depression are essential for fully understanding the pathogenesis of depression in humans. We made and analyzed a mouse model exhibiting social deficit and hyperphagia-like behavior using a subchronic and mild social defeat stress (sCSDS) paradigm. The body weight, food and water intake of mice were monitored during a test period, and their behaviors and serum components were analyzed at two stages: immediately after the sCSDS period and 1 month after the sCSDS. The body weight and food intake of defeated mice were significantly higher than control mice at the sCSDS period, and these differences were sustained until 1 month after the sCSDS, whereas the water intake of defeated mice was significantly higher than control mice for the period of sCSDS only. Behavioral analyses revealed that the defeated mice exhibit significant social aversion to unfamiliar mice in a social interaction test and a trend of anxiety-like behavior in an elevated-plus maze test. Possibly due to polydipsia-like symptoms, defeated mice had significantly lower levels of albumin and blood urea nitrogen than control mice immediately after the sCSDS period but not at 1 month after sCSDS. The present study revealed that our sCSDS mice keep much more water in their body than control mice. This study reports the first step toward an understanding of the mechanisms of stress-induced overhydration, over-eating and resultant weight gain.

  19. Mice Exposed to Chronic Intermittent Hypoxia Simulate Clinical Features of Deficiency of both Qi and Yin Syndrome in Traditional Chinese Medicine.

    PubMed

    Chai, Chengzhi; Kou, Junping; Zhu, Danni; Yan, Yongqing; Yu, Boyang

    2011-01-01

    Deficiency of both Qi and Yin Syndrome (DQYS) is one of the common syndromes in traditional Chinese medicine (TCM), mainly characterized by tiredness, emaciation, anorexia, fidget, palpitation and rapid pulse, and so forth. Currently, there is no available animal model which can reflect the clinical features of this syndrome. In the present paper, we observed the time-course changes of whole behavior, body weight, food intake, locomotive activity and electrocardiogram in mice exposed to chronic intermittent hypoxia for 6 weeks, and measured bleeding time at last according to the clinical features of DQYS and one key pathological factor. The results showed that the mice exposed to intermittent hypoxia for certain time presented lackluster hair, dull looking hair, resistance, attacking, body weight loss, food intake decline, locomotive activity decrease, heart rate quickening and T wave elevating, which were similar to the major clinical features of DQYS. Meanwhile, bleeding time shortening was also found, which was consistent with the clinical fact that DQYS often accompanied with blood stasis. The possible explanation was also outlined according to the available literature. Such findings suggested chronic intermittent hypoxia could induce similar symptoms and signs in mice accorded with the clinical features of DQYS, which provided a suitable animal model for evaluation of drugs for the treatment of this syndrome and further exploration of pathological process or correlation of the syndrome and related diseases.

  20. Decreased Levels of Proapoptotic Factors and Increased Key Regulators of Mitochondrial Biogenesis Constitute New Potential Beneficial Features of Long-lived Growth Hormone Receptor Gene–Disrupted Mice

    PubMed Central

    2013-01-01

    Decreased somatotrophic signaling is among the most important mechanisms associated with extended longevity. Mice homozygous for the targeted disruption of the growth hormone (GH) receptor gene (GH receptor knockout; GHRKO) are obese and dwarf, are characterized by a reduced weight and body size, undetectable levels of GH receptor, high concentration of serum GH, and greatly reduced plasma levels of insulin and insulin-like growth factor-I, and are remarkably long lived. Recent results suggest new features of GHRKO mice that may positively affect longevity—decreased levels of proapoptotic factors and increased levels of key regulators of mitochondrial biogenesis. The alterations in levels of the proapoptotic factors and key regulators of mitochondrial biogenesis were not further improved by two other potential life-extending interventions—calorie restriction and visceral fat removal. This may attribute the primary role to GH resistance in the regulation of apoptosis and mitochondrial biogenesis in GHRKO mice in terms of increased life span. PMID:23197187

  1. Meta-Analysis Identifies Gene-by-Environment Interactions as Demonstrated in a Study of 4,965 Mice

    PubMed Central

    Joo, Jong Wha J.; Shih, Diana; Davis, Richard C.; Lusis, Aldons J.; Eskin, Eleazar

    2014-01-01

    Identifying environmentally-specific genetic effects is a key challenge in understanding the structure of complex traits. Model organisms play a crucial role in the identification of such gene-by-environment interactions, as a result of the unique ability to observe genetically similar individuals across multiple distinct environments. Many model organism studies examine the same traits but under varying environmental conditions. For example, knock-out or diet-controlled studies are often used to examine cholesterol in mice. These studies, when examined in aggregate, provide an opportunity to identify genomic loci exhibiting environmentally-dependent effects. However, the straightforward application of traditional methodologies to aggregate separate studies suffers from several problems. First, environmental conditions are often variable and do not fit the standard univariate model for interactions. Additionally, applying a multivariate model results in increased degrees of freedom and low statistical power. In this paper, we jointly analyze multiple studies with varying environmental conditions using a meta-analytic approach based on a random effects model to identify loci involved in gene-by-environment interactions. Our approach is motivated by the observation that methods for discovering gene-by-environment interactions are closely related to random effects models for meta-analysis. We show that interactions can be interpreted as heterogeneity and can be detected without utilizing the traditional uni- or multi-variate approaches for discovery of gene-by-environment interactions. We apply our new method to combine 17 mouse studies containing in aggregate 4,965 distinct animals. We identify 26 significant loci involved in High-density lipoprotein (HDL) cholesterol, many of which are consistent with previous findings. Several of these loci show significant evidence of involvement in gene-by-environment interactions. An additional advantage of our meta

  2. Temporal evolution of neurophysiological and behavioral features of synapsin I/II/III triple knock-out mice.

    PubMed

    Cambiaghi, Marco; Cursi, Marco; Monzani, Elena; Benfenati, Fabio; Comi, Giancarlo; Minicucci, Fabio; Valtorta, Flavia; Leocani, Letizia

    2013-02-01

    Deletion of one or more synapsin genes in mice results in a spontaneous epilepsy. In these animals, seizures can be evoked by opening or moving the cage. Aim of the present study was to characterize the evolution of the epileptic phenotype by neurophysiological examination and behavioral observation in synapsin triple knock-out (Syn-TKO) mice. Syn-TKO mice were studied from 20 postnatal days (PND) up to 6 months of age by video-EEG recording and behavioral observation. Background EEG spectral analysis was performed and data were compared to WT animals. Syn-TKO revealed rare spontaneous seizures and increased susceptibility to evoked seizures in mice from 60 to 100 PND. Spontaneous and evoked seizures presented similar duration and morphology. At times, seizures were followed by a post-ictal phase characterized by a 4 Hz rhythmic activity and immobility of the animal. Spectral analysis of background EEG evidenced a slowing of the theta-alpha peak in Syn-TKO mice compared to WT mice within the period from PND 40 to 100. These data indicate that Syn-TKO mice do not exhibit a linear progression of the epileptic phenotype, with the period corresponding to a higher susceptibility to evoked seizures characterized by background EEG slowing. This aspect might be connected to brain dysfunction often associated to epilepsy in the interictal period.

  3. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1979-01-01

    Two demonstrations are presented: a verification of the discontinuity of matter based on the law of definite proportions, and a series of consecutive chemical reactions featuring reversible equilibria. (BB)

  4. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L.

    1982-01-01

    Two demonstrations are described: (1) a sunset effect using a gooseneck lamp and 20 sheets of paper and (2) the preparation and determination of structural features of dimethyl sulfoxide (DMSO) by infrared spectroscopy. (SK)

  5. Only minor differences in renal osteodystrophy features between wild-type and sclerostin knockout mice with chronic kidney disease.

    PubMed

    Cejka, Daniel; Parada-Rodriguez, Diego; Pichler, Stefanie; Marculescu, Rodrig; Kramer, Ina; Kneissel, Michaela; Gross, Thomas; Reisinger, Andreas; Pahr, Dieter; Monier-Faugere, Marie-Claude; Haas, Martin; Malluche, Hartmut H

    2016-10-01

    Renal osteodystrophy affects the majority of patients with advanced chronic kidney disease (CKD) and is characterized by progressive bone loss. This study evaluated the effects of sclerostin knockout on bone in a murine model of severe, surgically induced CKD in both sclerostin knockout and wild-type mice. Mice of both genotypes with normal kidney function served as controls. Tibiae were analyzed using micro-computed tomography, and lumbar vertebrae were analyzed by histomorphometry. Results were tested for statistical significance by 2-way ANOVA to investigate whether bone of the knockout mice reacted differently to CKD compared with bone of wild-type mice. In the tibiae, there was no difference after creation of CKD between wild-type and knockout animals for cortical thickness or cross-sectional moment of inertia. Increases in cortical porosity induced by CKD differed significantly between genotypes in the tibial metaphysis but not in the diaphysis. In the trabecular compartment, no difference in reaction to CKD between genotypes was found for bone volume, trabecular number, trabecular thickness, and trabecular separation. In the lumbar vertebrae, significant differences in response to CKD between wild-type and knockout mice were seen for both bone volume and trabecular thickness. Osteoblast parameters did not differ significantly, whereas osteoclast numbers significantly increased in the wild-type but significantly decreased in knockout mice with CKD. No differences in response to CKD between genotypes were found for bone formation rate or mineral apposition rate. Thus, complete absence of sclerostin has only minor effects on CKD-induced bone loss in mice. PMID:27528549

  6. Modulation of Specific Sensory Cortical Areas by Segregated Basal Forebrain Cholinergic Neurons Demonstrated by Neuronal Tracing and Optogenetic Stimulation in Mice.

    PubMed

    Chaves-Coira, Irene; Barros-Zulaica, Natali; Rodrigo-Angulo, Margarita; Núñez, Ángel

    2016-01-01

    Neocortical cholinergic activity plays a fundamental role in sensory processing and cognitive functions. Previous results have suggested a refined anatomical and functional topographical organization of basal forebrain (BF) projections that may control cortical sensory processing in a specific manner. We have used retrograde anatomical procedures to demonstrate the existence of specific neuronal groups in the BF involved in the control of specific sensory cortices. Fluoro-Gold (FlGo) and Fast Blue (FB) fluorescent retrograde tracers were deposited into the primary somatosensory (S1) and primary auditory (A1) cortices in mice. Our results revealed that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups. Most of the neurons located in the horizontal limb of the diagonal band of Broca (HDB) projected to the S1 cortex, indicating that this area is specialized in the sensory processing of tactile stimuli. However, the nucleus basalis magnocellularis (B) nucleus shows a similar number of cells projecting to the S1 as to the A1 cortices. In addition, we analyzed the cholinergic effects on the S1 and A1 cortical sensory responses by optogenetic stimulation of the BF neurons in urethane-anesthetized transgenic mice. We used transgenic mice expressing the light-activated cation channel, channelrhodopsin-2, tagged with a fluorescent protein (ChR2-YFP) under the control of the choline-acetyl transferase promoter (ChAT). Cortical evoked potentials were induced by whisker deflections or by auditory clicks. According to the anatomical results, optogenetic HDB stimulation induced more extensive facilitation of tactile evoked potentials in S1 than auditory evoked potentials in A1, while optogenetic stimulation of the B nucleus facilitated either tactile or auditory evoked potentials equally. Consequently, our results suggest that cholinergic projections to the cortex are organized into segregated

  7. Modulation of Specific Sensory Cortical Areas by Segregated Basal Forebrain Cholinergic Neurons Demonstrated by Neuronal Tracing and Optogenetic Stimulation in Mice

    PubMed Central

    Chaves-Coira, Irene; Barros-Zulaica, Natali; Rodrigo-Angulo, Margarita; Núñez, Ángel

    2016-01-01

    Neocortical cholinergic activity plays a fundamental role in sensory processing and cognitive functions. Previous results have suggested a refined anatomical and functional topographical organization of basal forebrain (BF) projections that may control cortical sensory processing in a specific manner. We have used retrograde anatomical procedures to demonstrate the existence of specific neuronal groups in the BF involved in the control of specific sensory cortices. Fluoro-Gold (FlGo) and Fast Blue (FB) fluorescent retrograde tracers were deposited into the primary somatosensory (S1) and primary auditory (A1) cortices in mice. Our results revealed that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups. Most of the neurons located in the horizontal limb of the diagonal band of Broca (HDB) projected to the S1 cortex, indicating that this area is specialized in the sensory processing of tactile stimuli. However, the nucleus basalis magnocellularis (B) nucleus shows a similar number of cells projecting to the S1 as to the A1 cortices. In addition, we analyzed the cholinergic effects on the S1 and A1 cortical sensory responses by optogenetic stimulation of the BF neurons in urethane-anesthetized transgenic mice. We used transgenic mice expressing the light-activated cation channel, channelrhodopsin-2, tagged with a fluorescent protein (ChR2-YFP) under the control of the choline-acetyl transferase promoter (ChAT). Cortical evoked potentials were induced by whisker deflections or by auditory clicks. According to the anatomical results, optogenetic HDB stimulation induced more extensive facilitation of tactile evoked potentials in S1 than auditory evoked potentials in A1, while optogenetic stimulation of the B nucleus facilitated either tactile or auditory evoked potentials equally. Consequently, our results suggest that cholinergic projections to the cortex are organized into segregated

  8. Modulation of Specific Sensory Cortical Areas by Segregated Basal Forebrain Cholinergic Neurons Demonstrated by Neuronal Tracing and Optogenetic Stimulation in Mice.

    PubMed

    Chaves-Coira, Irene; Barros-Zulaica, Natali; Rodrigo-Angulo, Margarita; Núñez, Ángel

    2016-01-01

    Neocortical cholinergic activity plays a fundamental role in sensory processing and cognitive functions. Previous results have suggested a refined anatomical and functional topographical organization of basal forebrain (BF) projections that may control cortical sensory processing in a specific manner. We have used retrograde anatomical procedures to demonstrate the existence of specific neuronal groups in the BF involved in the control of specific sensory cortices. Fluoro-Gold (FlGo) and Fast Blue (FB) fluorescent retrograde tracers were deposited into the primary somatosensory (S1) and primary auditory (A1) cortices in mice. Our results revealed that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups. Most of the neurons located in the horizontal limb of the diagonal band of Broca (HDB) projected to the S1 cortex, indicating that this area is specialized in the sensory processing of tactile stimuli. However, the nucleus basalis magnocellularis (B) nucleus shows a similar number of cells projecting to the S1 as to the A1 cortices. In addition, we analyzed the cholinergic effects on the S1 and A1 cortical sensory responses by optogenetic stimulation of the BF neurons in urethane-anesthetized transgenic mice. We used transgenic mice expressing the light-activated cation channel, channelrhodopsin-2, tagged with a fluorescent protein (ChR2-YFP) under the control of the choline-acetyl transferase promoter (ChAT). Cortical evoked potentials were induced by whisker deflections or by auditory clicks. According to the anatomical results, optogenetic HDB stimulation induced more extensive facilitation of tactile evoked potentials in S1 than auditory evoked potentials in A1, while optogenetic stimulation of the B nucleus facilitated either tactile or auditory evoked potentials equally. Consequently, our results suggest that cholinergic projections to the cortex are organized into segregated

  9. Loss of Magel2, a Candidate Gene for Features of Prader-Willi Syndrome, Impairs Reproductive Function in Mice

    PubMed Central

    Mercer, Rebecca E.; Wevrick, Rachel

    2009-01-01

    Background MAGEL2 is one of several genes typically inactivated in the developmental obesity disorder Prader-Willi syndrome (PWS). The physiological consequences of loss of MAGEL2, but without the concurrent loss of other PWS genes, are not well understood. Gene-targeted mutation of Magel2 in mice disrupts circadian rhythm and metabolism causing reduced total activity, reduced weight gain before weaning, and increased adiposity after weaning. Principal Findings We now show that loss of Magel2 in mice causes reduced fertility in both males and females through extended breeding intervals and early reproductive decline and termination. Female Magel2-null mice display extended and irregular estrous cycles, while males show decreased testosterone levels, and reduced olfactory preference for female odors. Conclusions Our results suggest that loss of MAGEL2 contributes to the reproductive deficits seen in people with PWS, and further highlights the role of normal circadian rhythm in the maintenance of fertility. PMID:19172181

  10. FVB/NJ mice demonstrate a youthful sensitivity to noise-induced hearing loss and provide a useful genetic model for the study of neural hearing loss.

    PubMed

    Ho, Maria K; Li, Xin; Wang, Juemei; Ohmen, Jeffrey D; Friedman, Rick A

    2014-01-01

    The hybrid mouse diversity panel (HMDP), a panel of 100 strains, has been employed in genome wide association studies (GWAS) to study complex traits in mice. Hearing is a complex trait and the CBA/CaJ mouse strain is a widely used model for age-related hearing loss (ARHI) and noise induced hearing loss (NIHL). The CBA/CaJ strain's youthful sensitivity to noise and limited age-related loss led us to attempt to identify additional strains segregating a similar phenotype for our panel. FVB/NJ is part of the HMDP and has been previously described as having a similar ARHI phenotype to CBA/CaJ. For these reasons, we have studied the FVB/NJ mouse for ARHI and NIHL phenotypes in hopes of incorporating its phenotype into HMDP studies. We demonstrate that FVB/NJ exhibits ARHI at an earlier age than CBA/CaJ and young FVB/NJ mice are vulnerable to NIHL up until 10 to 12 weeks. This suggests that FVB/NJ may be used as an additional genetic model for neural forms of progressive hearing loss and for the study of youthful sensitivity to noise.

  11. FVB/NJ mice demonstrate a youthful sensitivity to noise-induced hearing loss and provide a useful genetic model for the study of neural hearing loss

    PubMed Central

    Ho, Maria K.; Li, Xin; Wang, Juemei; Ohmen, Jeffrey D.; Friedman, Rick A.

    2014-01-01

    The hybrid mouse diversity panel (HMDP), a panel of 100 strains, has been employed in genome wide association studies (GWAS) to study complex traits in mice. Hearing is a complex trait and the CBA/CaJ mouse strain is a widely used model for age-related hearing loss (ARHI) and noise induced hearing loss (NIHL). The CBA/CaJ strain's youthful sensitivity to noise and limited age-related loss led us to attempt to identify additional strains segregating a similar phenotype for our panel. FVB/NJ is part of the HMDP and has been previously described as having a similar ARHI phenotype to CBA/CaJ. For these reasons, we have studied the FVB/NJ mouse for ARHI and NIHL phenotypes in hopes of incorporating its phenotype into HMDP studies. We demonstrate that FVB/NJ exhibits ARHI at an earlier age than CBA/CaJ and young FVB/NJ mice are vulnerable to NIHL up until 10 to 12 weeks. This suggests that FVB/NJ may be used as an additional genetic model for neural forms of progressive hearing loss and for the study of youthful sensitivity to noise. PMID:24707282

  12. Studies on visceral Leishmania tropica infection in BALB/c mice. I. Clinical features and cellular changes.

    PubMed Central

    Djoko-Tamnou, J; Leclerc, C; Modabber, F; Chedid, L

    1981-01-01

    The visceral and lethal infection produced in BALB/c mice by Leishmania tropica (major) is accompanied by splenomegaly, anaemia and reversal of albumin-to-globulin ratio. The percentages of both B and T cells are decreased in the spleen. The spleen and lymph nodes become populated with large Ig-, Thy 1.2- 'null' cells. The similarity of some of these parameters with those produced in human kala-azar is discussed. Images Fig. 1 PMID:7337976

  13. Carbohydrate-remodelled acid α-glucosidase with higher affinity for the cation-independent mannose 6-phosphate receptor demonstrates improved delivery to muscles of Pompe mice

    PubMed Central

    2005-01-01

    To enhance the delivery of rhGAA (recombinant GAA, where GAA stands for acid α-glucosidase) to the affected muscles in Pompe disease, the carbohydrate moieties on the enzyme were remodelled to exhibit a high affinity ligand for the CI-MPR (cation-independent M6P receptor, where M6P stands for mannose 6-phosphate). This was achieved by chemically conjugating on to rhGAA, a synthetic oligosaccharide ligand bearing M6P residues in the optimal configuration for binding the receptor. The carbonyl chemistry used resulted in the conjugation of approx. six synthetic ligands on to each enzyme. The resulting modified enzyme [neo-rhGAA (modified recombinant human GAA harbouring synthetic oligosaccharide ligands)] displayed near-normal specific activity and significantly increased affinity for the CI-MPR. However, binding to the mannose receptor was unaffected despite the introduction of additional mannose residues in neo-rhGAA. Uptake studies using L6 myoblasts showed neo-rhGAA was internalized approx. 20-fold more efficiently than the unmodified enzyme. Administration of neo-rhGAA into Pompe mice also resulted in greater clearance of glycogen from all the affected muscles when compared with the unmodified rhGAA. Comparable reductions in tissue glycogen levels in the Pompe mice were realized using an approx. 8-fold lower dose of neo-rhGAA in the heart and diaphragm and an approx. 4-fold lower dose in the skeletal muscles. Treatment of older Pompe mice, which are more refractory to enzyme therapy, with 40 mg/kg neo-rhGAA resulted in near-complete clearance of glycogen from all the affected muscles as opposed to only partial correction with the unmodified rhGAA. These results demonstrate that remodelling the carbohydrate of rhGAA to improve its affinity for the CI-MPR represents a feasible approach to enhance the efficacy of enzyme replacement therapy for Pompe disease. PMID:15839836

  14. Modeling bipolar disorder in mice by increasing acetylcholine or dopamine: Chronic lithium treats most, but not all features

    PubMed Central

    van Enkhuizen, Jordy; Milienne-Petiot, Morgane; Geyer, Mark A.; Young, Jared W.

    2015-01-01

    Rationale Bipolar disorder (BD) is a disabling and life-threatening disease characterized by states of depression and mania. New and efficacious treatments have not been forthcoming partly due to a lack of well-validated models representing both facets of BD. Objectives We hypothesized that cholinergic- and dopaminergic-pharmacological manipulations would model depression and mania respectively, each attenuated by lithium treatment. Methods C57BL/6J mice received the acetylcholinesterase inhibitor physostigmine or saline before testing for ‘behavioral despair’ (immobility) in the tail-suspension test (TST) and forced-swim test (FST). Physostigmine effects on exploration and sensorimotor gating were assessed using the cross-species behavioral pattern monitor (BPM) and prepulse inhibition (PPI) paradigms. Other C57BL/6J mice received chronic lithium drinking water (300, 600, or 1200 mg/l) before assessing their effects alone in the BPM or with physostigmine on FST performance. Another group was tested with acute GBR12909 (dopamine transporter inhibitor) and chronic lithium (1000 mg/l) in the BPM. Results Physostigmine (0.03 mg/kg) increased immobility in the TST and FST without affecting activity, exploration, or PPI. Lithium (600 mg/l) resulted in low therapeutic serum concentrations and normalized the physostigmine-increased immobility in the FST. GBR12909 induced mania-like behavior in the BPM of which hyper-exploration was attenuated, though not reversed, after chronic lithium (1000 mg/ml). Conclusions Increased cholinergic levels induced depression-like behavior and hyperdopaminergia induced mania-like behavior in mice, while chronic lithium treated some, but not all, facets of these effects. These data support a cholinergic-monoaminergic mechanism for modeling BD aspects and provide a way to assess novel therapeutics. PMID:26141192

  15. Influence of genetic dissimilarity of mother and fetus on progesterone concentrations in pregnant mice and adaptive features of offspring.

    PubMed

    Gerlinskaya, L A; Evsikov, V I

    2001-03-01

    Concentrations of progesterone in blood plasma and tissue were studied in pregnant mice of strains BALB/cLac and C57BL/6J. Both intra- and interstrain mating and embryo transplantations were used as models of homo- and heterotopic pregnancy. On day 4 of heterotopic pregnancy, plasma progesterone concentrations of females of both strains were higher than those in females of both strains undergoing homotopic pregnancy. In addition, tissue progesterone content of hybrid embryos was higher than that of purebred embryos. Adrenocortical responses to social conflict as indicators of stress resistance were studied in progeny aged 2-3 months. There was a minimal increase in plasma glucocorticoid concentrations in heterotopic transplantants after 15 min pair-matching tests and 30 min crowding compared with those of other progeny, including purebred male mice of BALB/cLac and C57BL/6J strains, homotransplantants and reciprocal hybrids. Thus, genetic dissimilarity of mother and fetuses plays an important role in progesterone provision during pregnancy and also modifies development of progeny. PMID:11226067

  16. THE PATHOGENESIS OF HERPES VIRUS ENCEPHALITIS. I. VIRUS PATHWAYS TO THE NERVOUS SYSTEM OF SUCKLING MICE DEMONSTRATED BY FLUORESCENT ANTIBODY STAINING.

    PubMed

    JOHNSON, R T

    1964-02-01

    The pathogenesis of herpes simplex virus encephalitis and myelitis was studied in suckling mice using routine titration procedures and fluorescent antibody staining for the identification of infected cells. After intracerebral inoculation virus was shown to disperse rapidly in the cerebrospinal fluid (CSF), multiply in meninges and ependyma, and then invade the underlying parenchyma infecting both neurons and glia. Following extraneural inoculation virus gained access to the central nervous system (CNS) by both hematogenous and neural pathways. After intraperitoneal and intranasal inoculation virus was found to multiply in viscera and produce viremia; foci of CNS infection then developed around small cerebral vessels. After subcutaneous and intranasal inoculation neural spread of virus was demonstrated along corresponding peripheral and cranial nerves. This spread resulted from the centripetal infection of endoneural cells (Schwann cells and fibroblasts). Antigen was not found in axons even after infection of the corresponding ganglion cell perikaryon. Subsequent spread within the CNS was unrelated to neural tracts, and there was no evidence of axonal spread of virus in the host-virus system studied. These findings are discussed in relation to previous and current theories of the viral "blood-brain barrier" and neural pathways of infection.

  17. [11C]-Labeled Metformin Distribution in the Liver and Small Intestine Using Dynamic Positron Emission Tomography in Mice Demonstrates Tissue-Specific Transporter Dependency.

    PubMed

    Jensen, Jonas B; Sundelin, Elias I; Jakobsen, Steen; Gormsen, Lars C; Munk, Ole L; Frøkiær, Jørgen; Jessen, Niels

    2016-06-01

    Metformin is the most commonly prescribed oral antidiabetic drug, with well-documented beneficial preventive effects on diabetic complications. Despite being in clinical use for almost 60 years, the underlying mechanisms for metformin action remain elusive. Organic cation transporters (OCT), including multidrug and toxin extrusion proteins (MATE), are essential for transport of metformin across membranes, but tissue-specific activity of these transporters in vivo is incompletely understood. Here, we use dynamic positron emission tomography with [(11)C]-labeled metformin ([(11)C]-metformin) in mice to investigate the role of OCT and MATE in a well-established target tissue, the liver, and a putative target of metformin, the small intestine. Ablation of OCT1 and OCT2 significantly reduced the distribution of metformin in the liver and small intestine. In contrast, inhibition of MATE1 with pyrimethamine caused accumulation of metformin in the liver but did not affect distribution in the small intestine. The demonstration of OCT-mediated transport into the small intestine provides evidence of direct effects of metformin in this tissue. OCT and MATE have important but separate roles in uptake and elimination of metformin in the liver, but this is not due to changes in biliary secretion. [(11)C]-Metformin holds great potential as a tool to determine the pharmacokinetic properties of metformin in clinical studies.

  18. Lipidomic profiling of phosphocholine-containing brain lipids in mice with sensorimotor deficits and anxiety-like features after exposure to Gulf War agents.

    PubMed

    Abdullah, Laila; Evans, James E; Bishop, Alex; Reed, Jon M; Crynen, Gogce; Phillips, John; Pelot, Robert; Mullan, Myles A; Ferro, Austin; Mullan, Christopher M; Mullan, Michael J; Ait-Ghezala, Ghania; Crawford, Fiona C

    2012-12-01

    The central nervous system (CNS)-based symptoms of Gulf War Illness (GWI) include motor dysfunction, anxiety, and cognitive impairment. Gulf War (GW) agents, such as pyridostigmine bromide (PB), permethrin (PER), N,N-diethyl-meta-toluamide (DEET), and stress, are among the contributory factors to the pathobiology of GWI. This study characterizes disturbances in phosphocholine-containing lipids that accompany neurobehavioral and neuropathological features associated with GW agent exposure. Exposed mice received PB orally, dermal application of PER and DEET and restraint stress daily for 28 days, while controls received vehicle during this period. Neurobehavioral studies included the rotarod, open field, and Morris water maze tests. Histopathological assessments included glial fibrillary acid protein, CD45, and Nissl staining. Liquid chromatography/mass spectrometry with source collision-induced dissociation in negative and positive ionization scanning modes was performed to characterize brain phosphatidylcholine (PC) and sphingomyelin (SM). A significant increase in ether containing PC (ePC34:0, ePC36:2, and ePC36:1) or long-chain fatty acid-containing PC (38:1, 40:4, 40:2) was observed in exposed mice compared with controls. Among differentially expressed PCs, levels of those with monounsaturated fatty acids were more affected than those with saturated and polyunsaturated fatty acids. Sensorimotor deficits and anxiety, together with an increase in astrocytosis, were observed in exposed mice compared with controls. These lipid changes suggest that alterations in peroxisomal pathways and stearoyl-CoA desaturase activity accompany neurobehavioral and neuropathological changes after GW agent exposure and represent possible treatment targets for the CNS symptoms of GWI.

  19. A Rodent Model of Chikungunya Virus Infection in RAG1 -/- Mice, with Features of Persistence, for Vaccine Safety Evaluation.

    PubMed

    Seymour, Robert L; Adams, A Paige; Leal, Grace; Alcorn, Maria D H; Weaver, Scott C

    2015-01-01

    Chikungunya virus (CHIKV) is a positive sense, single stranded RNA virus in the genus Alphavirus, and the etiologic agent of epidemics of severe arthralgia in Africa, Asia, Europe and, most recently, the Americas. CHIKV causes chikungunya fever (CHIK), a syndrome characterized by rash, fever, and debilitating, often chronic arthritis. In recent outbreaks, CHIKV has been recognized to manifest more neurologic signs of illness in the elderly and those with co-morbidities. The syndrome caused by CHIKV is often self-limited; however, many patients develop persistent arthralgia that can last for months or years. These characteristics make CHIKV not only important from a human health standpoint, but also from an economic standpoint. Despite its importance as a reemerging disease, there is no licensed vaccine or specific treatment to prevent CHIK. Many studies have begun to elucidate the pathogenesis of CHIKF and the mechanism of persistent arthralgia, including the role of the adaptive immune response, which is still poorly understood. In addition, the lack of an animal model for chronic infection has limited studies of CHIKV pathogenesis as well as the ability to assess the safety of vaccine candidates currently under development. To address this deficiency, we used recombination activating gene 1 (RAG1-/-) knockout mice, which are deficient in both T and B lymphocytes, to develop a chronic CHIKV infection model. Here, we describe this model as well as its use in evaluating the safety of a live-attenuated vaccine candidate.

  20. TU-A-12A-04: Quantitative Texture Features Calculated in Lung Tissue From CT Scans Demonstrate Consistency Between Two Databases From Different Institutions

    SciTech Connect

    Cunliffe, A; Armato, S; Castillo, R; Pham, N; Guerrero, T; Al-Hallaq, H

    2014-06-15

    Purpose: To evaluate the consistency of computed tomography (CT) scan texture features, previously identified as stable in a healthy patient cohort, in esophageal cancer patient CT scans. Methods: 116 patients receiving radiation therapy (median dose: 50.4Gy) for esophageal cancer were retrospectively identified. For each patient, diagnostic-quality pre-therapy (0-183 days) and post-therapy (5-120 days) scans (mean voxel size: 0.8mm×0.8mm×2.5mm) and a treatment planning scan and associated dose map were collected. An average of 501 32x32-pixel ROIs were placed randomly in the lungs of each pre-therapy scan. ROI centers were mapped to corresponding locations in post-therapy and planning scans using the displacement vector field output by demons deformable registration. Only ROIs with mean dose <5Gy were analyzed, as these were expected to contain minimal post-treatment damage. 140 texture features were calculated in pre-therapy and post-therapy scan ROIs and compared using Bland-Altman analysis. For each feature, the mean feature value change and the distance spanned by the 95% limits of agreement were normalized to the mean feature value, yielding normalized range of agreement (nRoA) and normalized bias (nBias). Using Wilcoxon signed rank tests, nRoA and nBias were compared with values computed previously in 27 healthy patient scans (mean voxel size: 0.67mm×0.67mm×1mm) acquired at a different institution. Results: nRoA was significantly (p<0.001) larger in cancer patients than healthy patients. Differences in nBias were not significant (p=0.23). The 20 features identified previously as having nRoA<20% for healthy patients had the lowest nRoA values in the current database, with an average increase of 5.6%. Conclusion: Despite differences in CT scanner type, scan resolution, and patient health status, the same 20 features remained stable (i.e., low variability and bias) in the absence of disease changes for databases from two institutions. Identification of

  1. Vertical Feature Mask Feature Classification Flag Extraction

    Atmospheric Science Data Center

    2013-03-28

      Vertical Feature Mask Feature Classification Flag Extraction This routine demonstrates extraction of the ... in a CALIPSO Lidar Level 2 Vertical Feature Mask feature classification flag value. It is written in Interactive Data Language (IDL) ...

  2. Use of mice tolerant to lipopolysaccharide to demonstrate requirement of cooperation between macrophages and lymphocytes to generate lipopolysaccharide-induced colony-stimulating factor in vivo.

    PubMed Central

    Williams, Z; Hertogs, C F; Pluznik, D H

    1983-01-01

    Injection of lipopolysaccharide (LPS) into mice was followed by a rapid elevation of colony-stimulating factor (CSF) in the serum. A second, challenging injection of LPS given 3 to 4 days later failed to induce elevated levels of CSF in the serum. Such mice tolerant to LPS were used as an experimental tool to identify the CSF-producing cells which respond to LPS. We observed that generation of LPS-induced CSF in mice tolerant to LPS could be restored by an intraperitoneal injection of spleen cells 24 h before the challenging injection of LPS. Depletion of the adherent cells from the spleen cells reduced the ability of the splenic lymphocytes to restore the capacity of the mice tolerant to LPS to generate serum CSF. Reconstitution of the splenic lymphocytes with 5% thioglycolate-elicited peritoneal macrophages, however, reestablished the restorative capacity of these cells, whereas almost no restoration was observed after direct injection of elicited peritoneal macrophages. These data suggest that the spleen cells are active in generating CSF, provided that macrophages are present and can interact with the splenic lymphocytes to generate LPS-induced CSF in the serum. PMID:6602767

  3. Direct demonstration of P-selectin- and VCAM-1-dependent mononuclear cell rolling in early atherosclerotic lesions of apolipoprotein E-deficient mice.

    PubMed

    Ramos, C L; Huo, Y; Jung, U; Ghosh, S; Manka, D R; Sarembock, I J; Ley, K

    1999-06-11

    Apolipoprotein E-deficient (ApoE-/-) mice develop atherosclerotic lesions throughout the arterial tree, including the carotid bifurcation. Although the expression of adhesion molecules such as ICAM-1, vascular cell adhesion molecule-1 (VCAM-1), and P-selectin on endothelium that overlie atherosclerotic plaques has been implicated in monocyte recruitment to developing lesions, monocyte adhesion in atherosclerotic vessels has not been observed directly. To investigate which adhesion molecules may be important in monocyte adhesion to atherosclerotic lesions, an isolated mouse carotid artery preparation was developed and perfused with mononuclear cells. We show rolling and attachment of the human monocytic cell line U937 and the mouse monocyte-macrophage cell line P388D1 in carotid arteries from 10- to 12-week-old ApoE-/- and C57BL/6 wild-type mice fed a Western-type diet (21% fat wt/wt) for 4 to 5 weeks. No rolling was observed in carotid arteries from C57BL/6 or BALB/c wild-type mice fed a chow diet and little was observed in BALB/c mice fed a Western-type diet. This model represents early lesion development as shown by minimal macrophage infiltration in the intima of carotid arteries from ApoE-/- mice fed a Western-type diet. Rolling was observed at shear stresses that were characteristic of the low-shear recirculation zone near the carotid bifurcation. Mononuclear cell attachment and rolling were significantly inhibited by monoclonal antibody blockade of P-selectin or its leukocyte ligand P-selectin glycoprotein ligand-1. Rolling velocities increased after monoclonal antibody blockade of mononuclear cell alpha4-integrin or VCAM-1, which indicates that alpha4-integrin interacting with VCAM-1 stabilizes rolling interactions and prolongs monocyte transit times.

  4. Near infrared lymphatic imaging demonstrates the dynamics of lymph flow and lymphangiogenesis during the acute vs. chronic phases of arthritis in mice

    PubMed Central

    Zhou, Quan; Wood, Ronald; Schwarz, Edward M.; Wang, Yong-Jun; Xing, Lianping

    2010-01-01

    Objective Development of an in vivo imaging method to assess lymphatic draining function in the K/B×N mouse model of inflammatory arthritis. Methods Indocyanine green (ICG), a near-infrared (NIR) fluorescent dye, was injected intradermally into the footpad of wild-type mice, the limb was illuminated with an 806 nm NIR laser, and the movement of ICG from the injection site to the draining popliteal lymph node (PLN) was recorded with a CCD camera. ICG-NIR images were analyzed to obtain 5 measures of lymphatic function across time. K/B×N arthritic mice and control non-arthritic littermates were imaged at one-month of age when acute joint inflammation commenced, and repeated at 3 months when joint inflammation became chronic. Lymphangiogenesis in PLNs was assessed by immunochemistry. Results ICG and its transport within lymphatic vessels were readily visualized and quantitative measures derived. During the acute phase of arthritis, the lymphatic vessels were dilated with increased ICG signal intensity and lymphatic pulses, and PLNs became fluorescent quickly. During the chronic phase, new lymphatic vessels were present near the foot. However, ICG appearance in lymphatic vessels was delayed. The size and area of PLN lymphatic sinuses progressively increased in the K/B×N mice. Conclusion ICG-NIR lymphatic imaging is a valuable method to assess the lymphatic draining function in mice with inflammatory arthritis. ICG-NIR imaging of K/B×N mice identified two distinct lymphatic phenotypes during the acute and chronic phase of inflammation. This technique can be used to assess new therapies for lymphatic disorders. PMID:20309866

  5. Transgenic Mice Expressing MCP-1 by the Urothelium Demonstrate Bladder Hypersensitivity, Pelvic Pain and Voiding Dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study

    PubMed Central

    Wang, Yaoqin; Lutgendorf, Susan; Bradley, Catherine; Schrepf, Andrew; Kreder, Karl; O'Donnell, Michael; Luo, Yi

    2016-01-01

    Monocyte chemoattractant protein-1 (MCP-1) is one of the key chemokines that play important roles in diverse inflammatory and chronic pain conditions. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating inflammatory condition of the urinary bladder characterized by the hallmark symptoms of pelvic pain and voiding dysfunction. To facilitate IC/BPS research, we used transgenic technology to develop a novel urothelial MCP-1 secretion mouse model (URO-MCP-1). A transgene consisting of the uroplakin II gene promoter and the mouse MCP-1 coding sequence with a secretory element was constructed and microinjected. URO-MCP-1 mice were found to express MCP-1 mRNA in the bladder epithelium and MCP-1 protein in the urine, and developed bladder inflammation 24 hours after intravesical administration of a single sub-noxious dose of lipopolysaccharide (LPS). The inflamed bladders of URO-MCP-1 mice exhibited elevated mRNAs for interleukin (IL)-1ß, IL-6, substance P precursor, and nerve growth factor as well as increased macrophage infiltration. In parallel with these phenotypic changes, URO-MCP-1 mice manifested significant functional changes at days 1 and 3 after cystitis induction. These functional changes included pelvic pain as measured by von Frey filament stimulation and voiding dysfunction (increased urinary frequency, reduced average volume voided per micturition, and reduced maximum volume voided per micturition) as measured by micturition cages. Micturition changes remained evident at day 7 after cystitis induction, although these changes were not statistically significant. Control wild-type C57BL/6 mice manifested no clear changes in histological, biochemical and behavioral features after similar cystitis induction with LPS. Taken together, our results indicate that URO-MCP-1 mice are hypersensitive to bladder irritants such as LPS and develop pelvic pain and voiding dysfunction upon cystitis induction, providing a novel model for IC

  6. Demonstration of skin friction measurements featuring in situ estimation of conduction loss using constant voltage anemometers and surface hot-films

    NASA Astrophysics Data System (ADS)

    Sarma, Garimella R.; Moes, Timothy R.

    2005-05-01

    The top of the 12.2m long NASA Dryden Flight Research Center's ground research vehicle (GRV) was used as a flat plate test bed for demonstrating an approach to measure skin friction. Using an array of surface hot-films operated by constant voltage anemometers (CVAs), the approach was demonstrated with in situ estimation of conduction heat loss from the hot-films to the substrate. An algebraic relationship, using the channel calibration constants a and b (determined a priori) with CVA output voltages Vs and Vw from that channel, is used for the estimation of the required quantities and lead resistance (rL) of the hot-film measured on site. Estimates of the power dissipated in the hot-film alone (Phf) (excluding the lead resistances), in situ resistance (Rw) of the hot-film due to applied overheat and flow, and the cold resistance (Ra) of the same hot-film at the ambient temperature are so obtained. Different approaches to estimate the in situ cold resistance (which is the resistance without any self-heating) of the hot-film are presented addressing the suitability of the procedure for flight applications as well. Tests were performed at several speeds of the GRV on the tarmac of a runway at the flight test center. The measured values are fitted to the classical (1/3) law equation with the computational dimensional skin friction (τ) obtained using the empirical local skin friction law for the long flat plate. There was an excellent (1/3) law fit in all the hot-films, demonstrating that the measured values fit classical theory. Using this measured fit with the theoretical values, calibration coefficients (A and B) for dimensional skin friction (τ) were obtained. Using these calibration coefficients, measured values were then converted to nondimensional local skin friction coefficients cf for all the hot-films at all speeds. Measured cf values agree well with the associated flat plate theory. Since the in situ measurement of heat loss to the substrate should ideally

  7. Cloning and sequencing of yajC and secD homologs of Brucella abortus and demonstration of immune responses to YajC in mice vaccinated with B. abortus RB51.

    PubMed

    Vemulapalli, R; Duncan, A J; Boyle, S M; Sriranganathan, N; Toth, T E; Schurig, G G

    1998-12-01

    To identify Brucella antigens that are potentially involved in stimulating a protective cell-mediated immune response, a gene library of Brucella abortus 2308 was screened for the expression of antigens reacting with immunoglobulin G2a antibodies from BALB/c mice vaccinated with B. abortus RB51. One selected positive clone (clone MCB68) contained an insert of 2.6 kb; nucleotide sequence analysis of this insert revealed two open reading frames (ORFs). The deduced amino acid sequences of the first and second ORFs had significant similarities with the YajC and SecD proteins, respectively, of several bacterial species. Both the YajC and SecD proteins were expressed in Escherichia coli as fusion proteins with maltose binding protein (MBP). In Western blots, sera from mice vaccinated with B. abortus RB51 recognized YajC but not SecD. Further Western blot analysis with purified recombinant YajC protein indicated that mice inoculated with B. abortus 19 or 2308 or B. melitensis RM1 also produced antibodies to YajC. In response to in vitro stimulation with recombinant MBP-YajC fusion protein, splenocytes from mice vaccinated with B. abortus RB51 were able to proliferate and produce gamma interferon but not interleukin-4. This study demonstrates, for the first time, the involvement of YajC protein in an immune response to an infectious agent.

  8. H9c2 and HL-1 cells demonstrate distinct features of energy metabolism, mitochondrial function and sensitivity to hypoxia-reoxygenation

    PubMed Central

    Kuznetsov, Andrey V.; Javadov, Sabzali; Sickinger, Stephan; Frotschnig, Sandra; Grimm, Michael

    2015-01-01

    Dysfunction of cardiac energy metabolism plays a critical role in many cardiac diseases, including heart failure, myocardial infarction and ischemia–reperfusion injury and organ transplantation. The characteristics of these diseases can be elucidated in vivo, though animal-free in vitro experiments, with primary adult or neonatal cardiomyocytes, the rat ventricular H9c2 cell line or the mouse atrial HL-1 cells, providing intriguing experimental alternatives. Currently, it is not clear how H9c2 and HL-1 cells mimic the responses of primary cardiomyocytes to hypoxia and oxidative stress. In the present study, we show that H9c2 cells are more similar to primary cardiomyocytes than HL-1 cells with regard to energy metabolism patterns, such as cellular ATP levels, bioenergetics, metabolism, function and morphology of mitochondria. In contrast to HL-1, H9c2 cells possess beta-tubulin II, a mitochondrial isoform of tubulin that plays an important role in mitochondrial function and regulation. We demonstrate that H9c2 cells are significantly more sensitive to hypoxia-reoxygenation injury in terms of loss of cell viability and mitochondrial respiration, whereas HL-1 cells were more resistant to hypoxia as evidenced by their relative stability. In comparison to HL-1 cells, H9c2 cells exhibit a higher phosphorylation (activation) state of AMP-activated protein kinase, but lower peroxisome proliferator-activated receptor gamma coactivator 1-alpha levels, suggesting that each cell type is characterized by distinct regulation of mitochondrial biogenesis. Our results provide evidence that H9c2 cardiomyoblasts are more energetically similar to primary cardiomyocytes than are atrial HL-1 cells. H9c2 cells can be successfully used as an in vitro model to simulate cardiac ischemia–reperfusion injury. PMID:25450968

  9. Effects of tea, decaffeinated tea, and caffeine on UVB light-induced complete carcinogenesis in SKH-1 mice: demonstration of caffeine as a biologically important constituent of tea.

    PubMed

    Huang, M T; Xie, J G; Wang, Z Y; Ho, C T; Lou, Y R; Wang, C X; Hard, G C; Conney, A H

    1997-07-01

    Oral administration of green or black tea inhibited UVB light-induced complete carcinogenesis in the skin of SKH-1 mice. Green tea was a more effective inhibitor than black tea. Oral administration of decaffeinated green or black tea resulted in substantially less inhibitory activity than did administration of the regular teas, and in one experiment, administration of a high-dose level of the decaffeinated teas enhanced the tumorigenic effect of UVB. Oral administration of caffeine alone had a substantial inhibitory effect on UVB-induced carcinogenesis, and adding caffeine to the decaffeinated teas restored the inhibitory effects of these teas on UVB-induced carcinogenesis. In additional studies, topical application of a green tea polyphenol fraction after each UVB application inhibited UVB-induced tumorigenesis. The results indicate that caffeine contributes in an important way to the inhibitory effects of green and black tea on UVB-induced complete carcinogenesis.

  10. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1984-01-01

    Procedures for two demonstrations are presented. The first is a demonstration of chemiluminescence. The second is a demonstration using a secondary battery constructed from common household articles. (JN)

  11. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1978-01-01

    Presents the following chemistry lecture demonstrations and experiments: (1) a versatile kinetic demonstration; (2) the Bakelite Demonstration; (3) applying Beer's law; and (4) entropy calculations. (HM)

  12. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1988-01-01

    Details three demonstrations for use in chemistry classrooms. Includes: "A Demonstration of Corrosion by Differential Aeration"; "A Simple Demonstration of the Activation Energy Concept"; and "A Boiling Demonstration at Room Temperature." Each description includes equipment, materials, and methods. (CW)

  13. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1988-01-01

    Describes two chemistry demonstrations including a demonstration of chemical inhibition and "The Rayleigh Fountain" which demonstrates the polarity of the water molecule. Provides instructions and explanations for each demonstration. (CW)

  14. Cell volume control in phospholemman (PLM) knockout mice: do cardiac myocytes demonstrate a regulatory volume decrease and is this influenced by deletion of PLM?

    PubMed

    Bell, James R; Lloyd, David; Curl, Claire L; Delbridge, Lea M D; Shattock, Michael J

    2009-03-01

    In addition to modulatory actions on Na+-K+-ATPase, phospholemman (PLM) has been proposed to play a role in cell volume regulation. Overexpression of PLM induces ionic conductances, with 'PLM channels' exhibiting selectivity for taurine. Osmotic challenge of host cells overexpressing PLM increases taurine efflux and augments the cellular regulatory volume decrease (RVD) response, though a link between PLM and cell volume regulation has not been studied in the heart. We recently reported a depressed cardiac contractile function in PLM knockout mice in vivo, which was exacerbated in crystalloid-perfused isolated hearts, indicating that these hearts were osmotically challenged. To address this, the present study investigated the role of PLM in osmoregulation in the heart. Isolated PLM wild-type and knockout hearts were perfused with a crystalloid buffer supplemented with mannitol in a bid to prevent perfusate-induced cell swelling and maintain function. Accordingly, and in contrast to wild-type control hearts, contractile function was improved in PLM knockout hearts with 30 mM mannitol. To investigate further, isolated PLM wild-type and knockout cardiomyocytes were subjected to increasing hyposmotic challenges. Initial validation studies showed the IonOptix video edge-detection system to be a simple and accurate 'real-time' method for tracking cell width as a marker of cell size. Myocytes swelled equally in both genotypes, indicating that PLM, when expressed at physiological levels in cardiomyocytes, is not essential to limit water accumulation in response to a hyposmotic challenge. Interestingly, freshly isolated adult cardiomyocytes consistently failed to mount RVDs in response to cell swelling, adding to conflicting reports in the literature. A proposed perturbation of the RVD response as a result of the cell isolation process was not restored, however, with short-term culture in either adult or neonatal cardiomyocytes.

  15. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1988-01-01

    Describes three flame test demonstrations including "Student-Presented Demonstrations on the Colors of Transition Metal Complexes,""A Flame Test Demonstration Device," and "Vivid Flame Tests." Preparation and procedures are discussed. Included in the first demonstration is an evaluation scheme for grading student demonstrations. (CW)

  16. [Features of behavioral reactions of chronically irradiated mice in the raised crosswise labyrinth with various genetically determined radiosensitivity and possibilities of their modification by the fungal biopolymer complex].

    PubMed

    Seniuk, O F; Gorovoĭ, L F; Kovalev, V A; Palamar, L A; Krul', N I; Zhidkov, A V; Chemerskiĭ, G F; Kireev, S I; Khatuntseva, I V

    2013-01-01

    Structural elements of the central nervous system--neurons, along with the higher neuroendocrine structures and the hypothalamus centres, show high sensitivity to a chronic action of low doses of ionizing radiation (IR) in view of their extreme enrichment by phospholipids and intensive supply by oxygen, creating favorable conditions for the development of oxidizing stress. Stressful influences cause negative emotions in the behaviour of animals manifested as fear or uneasiness. The study represents the results of comparative research into the behavioral reactions characterized by uneasiness in the Balb/c and C57bl/6 mice exposed to a chronic irradiation at low doses. The chitin-melanin-glucan complex from fungi Fomes fomentarius (ChMG) was approved as an adaptive agent. It has been shown that under identical conditions, deposition levels of radionuclides 137Cs and 90Sr are raised in mice with IR hypersensitivity--line Balb/c, in comparison with less radio sensitive mice--line C57bl/6. Simultaneously, Balb/c mice were observed to exhibit the signs of a more anxious behaviour in the new environment. Chronic external and internal radiation exposure to rare ionizing radiation at low doses promotes strengthening of anxiety and phobic reactions in mice with IR hypersensitivity. The use of ChMG in animals neutralized the increase in anxiety and phobic reactions after a prolonged irradiation, thus indicating the presence in ChMG of the anxiolitic activity along with the above mentioned powerful radiosorbent, antioxidant, gene protective and immunomodulatory properties.

  17. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1982-01-01

    Three chemistry demonstrations are described: (1) partition coefficients; (2) Rutherford simulation experiment; and (3) demonstration of the powerful oxidizing property of dimanganeseheptoxide. Background information, materials needed, and procedures are provided for each demonstration. (JN)

  18. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1987-01-01

    Presented are three demonstrations for chemical education. The activities include: (1) demonstration of vapor pressure; (2) a multicolored luminol-based chemiluminescence demonstration; and (3) a Charles's Law/Vapor pressure apparatus. (RH)

  19. Reflectance Demonstration.

    ERIC Educational Resources Information Center

    Kowalski, Frank

    1993-01-01

    Presents a demonstration in which a mirror "disappears" upon rotation. The author has used the demonstration with students from fourth grade up through college. Suggestions are given for making the demonstration into a permanent hallway display. (MVL)

  20. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1981-01-01

    Provides procedures for demonstrations: (1) the ferrioxalate actinometer, which demonstrates a photochemical reaction; and (2) the silver mirror, which demonstrates the reduction of a metal salt to the metal and/or the reducing power of sugars. (CS)

  1. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1988-01-01

    This article details two demonstrations involving color changes. Included are "Manganese Color Reactions" and "Flame Colors Demonstration." Include a list of materials needed, procedures, cautions, and results. (CW)

  2. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1985-01-01

    Background information (including chemical reactions) and procedures used are provided for (1) three buffer demonstrations and (2) a demonstration of phase transfer catalysis and carbanion formation. (JN)

  3. Tested Demonstrations

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1977-01-01

    Three demonstrations are described: paramagnetic properties of Fe(11) and Fe(111), the preparation of polyurethane foam: a lecture demonstration and the electrolysis of water-fuel cell reactions. A small discussion of the concepts demonstrated is included in each demonstration's description. (MR)

  4. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1988-01-01

    Describes two demonstrations for college level chemistry courses including: "Electrochemical Cells Using Sodium Silicate" and "A Simple, Vivid Demonstration of Selective Precipitation." Lists materials, preparation, procedures, and precautions. (CW)

  5. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1981-01-01

    Two demonstrations are described: (1) red cabbage and electrolysis of water to bring together acid/base and electrochemical concepts; and (2) a model to demonstrate acid/base conjugate pairs utilizing magnets. (SK)

  6. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1981-01-01

    Presents: (1) a simple demonstration which illustrates the driving force of entropy using the familiar effects of the negative thermal expansion coefficient of rubber; and (2) a demonstration of tetrahedral bonding using soap films. (CS)

  7. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1989-01-01

    Presented are two demonstrations including a variation of the iodine clock reaction, and a simple demonstration of refractive index. The materials, procedures, and a discussion of probable results are given for each. (CW)

  8. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1990-01-01

    Presented are two demonstrations; "Heat of Solution and Colligative Properties: An Illustration of Enthalpy and Entropy," and "A Vapor Pressure Demonstration." Included are lists of materials and experimental procedures. Apparatus needed are illustrated. (CW)

  9. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1978-01-01

    Presents two demonstrations; one on Boyle's Law, to illustrate the gas law and serve as a challenging problem for the students; the other is a modified Color Blind Traffic Light demonstration in which the oscillating reactions were speeded up. (GA)

  10. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1987-01-01

    Provides instructions on conducting four demonstrations for the chemistry classroom. Outlines procedures for demonstrations dealing with coupled oscillations, the evaporation of liquids, thioxanthone sulfone radical anion, and the control of variables and conservation of matter. (TW)

  11. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1978-01-01

    Two demonstrations are described which are suitable for introductory chemistry classes. The first involves the precipitation of silver, and the second is a demonstration of the relationship between rate constants and equilibrium constants using water and beakers. (BB)

  12. Demonstrating Diffusion

    ERIC Educational Resources Information Center

    Foy, Barry G.

    1977-01-01

    Two demonstrations are described. Materials and instructions for demonstrating movement of molecules into cytoplasm using agar blocks, phenolphthalein, and sodium hydroxide are given. A simple method for demonstrating that the rate of diffusion of a gas is inversely proportional to its molecular weight is also presented. (AJ)

  13. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1986-01-01

    Describes a demonstration involving the controlled combustion of a mixture of metals with black and smokeless powder in a small Erlenmeyer flask. Also describes demonstrations using a device that precludes breathing of hazardous vapors during class demonstrations; the device is easy to transport and use in rooms without sinks. (JN)

  14. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1986-01-01

    Describes two demonstrations used in laboratory chemistry courses. Discusses a "pH-activated" display used to chemically and visually supplement lecture demonstrations. Outlines another demonstration designed to show that copper(II) chloride is made of two ions, blue and yellow, which are combined to produce green. (TW)

  15. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Sands, Robert; And Others

    1982-01-01

    Procedures for two demonstrations are provided. The solubility of ammonia gas in water is demonstrated by introducing water into a closed can filled with the gas, collapsing the can. The second demonstration relates scale of standard reduction potentials to observed behavior of metals in reactions with hydrogen to produce hydrogen gas. (Author/JN)

  16. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1987-01-01

    Describes two classroom chemistry demonstrations which focus on the descriptive chemistry of bromine and iodine. Outlines the chemicals and equipment needed, experimental procedures, and discussion of one demonstration of the oxidation states of bromine and iodine, and another demonstration of the oxidation states of iodine. (TW)

  17. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1985-01-01

    List of materials needed, procedures used, and results obtained are provided for two demonstrations. The first is an inexpensive and quick method for demonstrating column chromatography of plant pigments of spinach extract. The second is a demonstration of cathodic protection by impressed current. (JN)

  18. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1983-01-01

    Free radical chlorination of methane is used in organic chemistry to introduce free radical/chain reactions. In spite of its common occurrence, demonstrations of the reaction are uncommon. Therefore, such a demonstration is provided, including background information, preparation of reactants/reaction vessel, introduction of reactants, irradiation,…

  19. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1986-01-01

    Provides three descriptions of demonstrations used in various chemistry courses. Includes the use of a simple demonstration model to illustrate principles of chromatography, techniques for using balloons to teach about the behavior of gases, and the use of small concentrations of synthetic polyelectrolytes to induce the flocculation hydrophobic…

  20. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1986-01-01

    Outlines a simple, inexpensive way of demonstrating electroplating using the reaction between nickel ions and copper metal. Explains how to conduct a demonstration of the electrolysis of water by using a colored Na2SO4 solution as the electrolyte so that students can observe the pH changes. (TW)

  1. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1990-01-01

    Presented are three demonstrations: "The Construction and Use of Commercial Voltaic Cell Displays in Freshman Chemistry"; Dramatizing Isotopes: Deuterated Ice Cubes Sink"; and "A Simple Apparatus to Demonstrate Differing Gas Diffusion Rates (Graham's Law)." Materials, procedures, and safety considerations are discussed. (CW)

  2. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1980-01-01

    Described is a demonstration utilized to measure the heat of vaporization using the Clausius-Clapeyron equation. Explained is that when measurement is made as part of a demonstration, it raises student's consciousness that chemistry is experimentally based. (Author/DS)

  3. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1982-01-01

    Three chemistry demonstrations are described: (1) modification of copper catalysis demonstration apparatus; (2) experiments in gas-liquid chromatography with simple gas chromatography at room temperature; and (3) equilibria in silver arsenate-arsenic acid and silver phosphate-phosphoric acid systems. Procedures and materials needed are provided.…

  4. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1989-01-01

    Presented are two chemistry demonstrations: (1) an alternative method for the demonstration of the properties of alkali metals, water is added to small amounts of metal; (2) an exploration of the properties of hydrogen, helium, propane, and carbon dioxide using an open trough and candle. (MVL)

  5. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1990-01-01

    Described are demonstrations designed to reveal the important "nonsolvent" properties of water through its interaction with a toy called "Magic Sand" and other synthetic silica derivatives, especially those bonded with organic moities. The procedures for seven demonstrations along with a discussion of the effects are presented. (CW)

  6. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1980-01-01

    Two demonstrations are described: (1) a variant of preparing purple benzene by phase transfer catalysis with quaternary ammonium salts and potassium permanganate in which crown ethers are used; (2) a corridor or "hallway" demonstration in which unknown molecular models are displayed and prizes awarded to students correctly identifying the…

  7. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1983-01-01

    Describes a lecture demonstration of a solid state phase transition using a thermodynamic material which changes state at room temperature. Also describes a demonstration on kinetics using a "Big Bang" (trade mark) calcium carbide cannon. Indicates that the cannon is safe to use. (JN)

  8. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1983-01-01

    Provides directions for setup and performance of two demonstrations. The first demonstrates the principles of Raoult's Law; using a simple apparatus designed to measure vapor pressure. The second illustrates the energy available from alcohol combustion (includes safety precautions) using an alcohol-fueled missile. (JM)

  9. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1979-01-01

    Presents two demonstrations for classroom use related to precipitation of ferrous hydroxide and to variation of vapor pressure with temperature. The former demonstration is simple and useful when discussing solubility of ionic compounds electrode potential of transition elements, and mixed valence compounds. (Author/SA)

  10. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1983-01-01

    Discusses a supplement to the "water to rose" demonstration in which a pink color is produced. Also discusses blood buffer demonstrations, including hydrolysis of sodium bicarbonate, simulated blood buffer, metabolic acidosis, natural compensation of metabolic acidosis, metabolic alkalosis, acidosis treatment, and alkalosis treatment. Procedures…

  11. Complete Demonstration.

    ERIC Educational Resources Information Center

    Yelon, Stephen; Maddocks, Peg

    1986-01-01

    Describes four-step approach to educational demonstration: tell learners they will have to perform; what they should notice; describe each step before doing it; and require memorization of steps. Examples illustrate use of this process to demonstrate a general mental strategy, and industrial design, supervisory, fine motor, and specific…

  12. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1987-01-01

    Describes two laboratory demonstrations in chemistry. One uses dry ice, freon, and freezer bags to demonstrate volume changes, vapor-liquid equilibrium, a simulation of a rain forest, and vaporization. The other uses the clock reaction technique to illustrate fast reactions and kinetic problems in releasing carbon dioxide during respiration. (TW)

  13. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1984-01-01

    Background information and procedures are provided for a second part to the dichromate volcano demonstration. The green ash produced during the demonstration is reduced to metal using aluminothermy (Goldschmide process). Also describes suitable light sources and spectroscopes for student observation of emission spectra in lecture halls. (JN)

  14. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1986-01-01

    Describes two demonstrations designed to help chemistry students visualize certain chemical properties. One experiment uses balloons to illustrate the behavior of gases under varying temperatures and pressures. The other uses a makeshift pea shooter and a commercial model to demonstrate atomic structure and the behavior of high-speed particles.…

  15. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1989-01-01

    Provided are two demonstrations for an introductory course in chemistry. The first one emphasizes the observation and the interpretation of facts to form hypotheses during the heating of a beaker of water. The second demonstration shows the liquid phase of carbon dioxide using dry ice and a pressure gauge. (YP)

  16. Green coffee polyphenols do not attenuate features of the metabolic syndrome and improve endothelial function in mice fed a high fat diet.

    PubMed

    Li Kwok Cheong, J D; Croft, K D; Henry, P D; Matthews, V; Hodgson, J M; Ward, N C

    2014-10-01

    We have investigated the effects of the major polyphenol in coffee, chlorogenic acid (CGA), on obesity, glucose intolerance, insulin resistance, systemic oxidative stress and endothelial dysfunction in a mouse model of the metabolic syndrome. Thirty C57BL6 mice were randomly divided into (n=10/group) (i) normal diet (ND), (ii) high fat diet (HFD), or (iii) high fat diet supplemented with 0.5% w/w green coffee bean extract (GCE) rich in chlorogenic acid (HFD+GCE). The high fat diet consisted of 28% fat and all animals were maintained on their diets for 12 weeks. The mice fed a HFD and HFD+GCE displayed symptoms of the metabolic syndrome compared to their normal fed counterparts, although no endothelial dysfunction was detected in the abdominal aortas after 12 weeks. GCE did not attenuate HFD-induced obesity, glucose intolerance, insulin resistance or systemic oxidative stress. Furthermore, GCE did not protect against ex vivo oxidant (hypochlorous acid)-induced endothelial dysfunction.

  17. Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice.

    PubMed

    Papadopoulou, Aikaterini S; Serneels, Lutgarde; Achsel, Tilmann; Mandemakers, Wim; Callaerts-Vegh, Zsuzsanna; Dooley, James; Lau, Pierre; Ayoubi, Torik; Radaelli, Enrico; Spinazzi, Marco; Neumann, Melanie; Hébert, Sébastien S; Silahtaroglu, Asli; Liston, Adrian; D'Hooge, Rudi; Glatzel, Markus; De Strooper, Bart

    2015-01-01

    miR-29 is expressed strongly in the brain and alterations in expression have been linked to several neurological disorders. To further explore the function of this miRNA in the brain, we generated miR-29a/b-1 knockout animals. Knockout mice develop a progressive disorder characterized by locomotor impairment and ataxia. The different members of the miR-29 family are strongly expressed in neurons of the olfactory bulb, the hippocampus and in the Purkinje cells of the cerebellum. Morphological analysis showed that Purkinje cells are smaller and display less dendritic arborisation compared to their wildtype littermates. In addition, a decreased number of parallel fibers form synapses on the Purkinje cells. We identified several mRNAs significantly up-regulated in the absence of the miR-29a/b-1 cluster. At the protein level, however, the voltage-gated potassium channel Kcnc3 (Kv3.3) was significantly up-regulated in the cerebella of the miR-29a/b knockout mice. Dysregulation of KCNC3 expression may contribute to the ataxic phenotype. PMID:25315682

  18. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1979-01-01

    Presents a recipe for the Nylon Rope Trick, which is considered to be one of the most spectacular demonstrations in chemistry. Materials for growing the polymer and some safety precautions are given. (SA)

  19. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L.

    1990-01-01

    Included are three demonstrations that include the phase change of ice when under pressure, viscoelasticity and colloid systems, and flame tests for metal ions. The materials, procedures, probable results, and applications to real life situations are included. (KR)

  20. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1987-01-01

    Describes two demonstrations suitable for chemistry instruction. One involves fractal structures obtained by electrodeposition of silver at an air-water interface and the other deals with molecular weights and music. (TW)

  1. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1986-01-01

    Background information, list of materials needed, and procedures used are provided for a demonstration involving the transformation of a hydrophobic liquid to a partially hydrophobic semisolid. Safety considerations are noted. (JN)

  2. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Roffia, Sergio; And Others

    1988-01-01

    Reports two electrochemical demonstrations. Uses a hydrogen-oxygen fuel cell to power a clock. Includes description of methods and materials. Investigates the "potato clock" used with different fruits. Lists emf and current for various fruit and electrode combinations. (ML)

  3. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1980-01-01

    Presented is a Corridor Demonstration which can be set up in readily accessible areas such as hallways or lobbies. Equipment is listed for a display of three cells (solar cells, fuel cells, and storage cells) which develop electrical energy. (CS)

  4. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Rehfeld, D. W.; And Others

    1988-01-01

    Describes two demonstrations (1) a dust explosion using a coffee can, candle, rubber tubing, and cornstarch and (2) forming a silicate-polyvinyl alcohol polymer which can be pressed into plastic sheets or molded. Gives specific instructions. (MVL)

  5. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1987-01-01

    Presents three demonstrations suitable for undergraduate chemistry classes. Focuses on experiments with calcium carbide, the induction by iron of the oxidation of iodide by dichromate, and the classical iodine clock reaction. (ML)

  6. Tested Demonstrations

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1977-01-01

    Describes a room-temperature method for demonstrating phosphorescence by including samples in a polymer matrix. Also discusses the Old Nassau Reaction, a clock reaction which turns orange then black. (MLH)

  7. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1988-01-01

    Describes two demonstrations for use in college chemistry classes. Includes "Spectroscopy in Large Lecture Halls" and "The Endothermic Dissolution of Ammonium Nitrate." Gives materials lists and procedures as well as a discussion of the results. (CW)

  8. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1987-01-01

    Describes two demonstrations for use in chemistry instruction. The first illustrates the preparation of a less common oxide of iron, showing why this oxide is rare. The second is an explosion reaction of hydrogen and oxygen that is recommended for use as an attention-getting device. (TW)

  9. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1981-01-01

    Provides instructions and a list of materials needed to demonstrate: (1) a model of the quantum mechanical atom; (2) principles involved in metal corrosion and in the prevention of this destructive process by electrochemical means; and (3) a Thermit reaction, modified to make it more dramatic and interesting for students. (SK)

  10. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1985-01-01

    Background information, procedures, and typical results obtained are provided for two demonstrations. The first involves the colorful complexes of copper(II). The second involves reverse-phase separation of Food, Drug, and Cosmetic (FD & C) dyes using a solvent gradient. (JN)

  11. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Cliche, Jean-Marie; And Others

    1988-01-01

    Describes two demonstrations: 1) the effect of polarity on solubility using sodium dichromate, TTE, ligroin, and water to form nonpolar-polar-nonpolar layers with the polar layer being colored; 2) determination of egg whites to be yellow by determining the content of yellow colored riboflavin in the egg white. (MVL)

  12. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1987-01-01

    Describes two demonstrations to illustrate characteristics of substances. Outlines a method to detect the changes in pH levels during the electrolysis of water. Uses water pistols, one filled with methane gas and the other filled with water, to illustrate the differences in these two substances. (TW)

  13. Tested Demonstrations

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1976-01-01

    Describes two demonstrations: one that illustrates the attainment of equilibrium in first-order reactions by changing the volumes of two beakers of water at a specified rate, and another that illustrates the role of indicators in showing pH changes in buffer solutions. (MLH)

  14. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1985-01-01

    Describes two demonstrations that require almost no preparation time, are visually stimulating, and present a variety of material for class discussion (with sample questions provided). The first involves a sodium bicarbonate hydrochloric acid volcano; the second involves a dissolving polystyrene cup. Procedures used and information on…

  15. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L.

    1983-01-01

    An apparatus is described in which effects of pressure, volume, and temperature changes on a gas can be observed simultaneously. Includes use of the apparatus in demonstrating Boyle's, Gay-Lussac's, and Charles' Laws, attractive forces, Dalton's Law of Partial pressures, and in illustrating measurable vapor pressures of liquids and some solids.…

  16. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1984-01-01

    Two demonstrations are described. The first shows the effect of polarity on solubility. The second is based on the unexpected formation of a precipitate of barium nitrate when barium carbonate or barium phosphate is treated with dilute nitric acid. List of materials needed and procedures used are included. (JN)

  17. Development and functional evaluation of biomimetic silicone surfaces with hierarchical micro/nano-topographical features demonstrates favourable in vitro foreign body response of breast-derived fibroblasts.

    PubMed

    Kyle, Daniel J T; Oikonomou, Antonios; Hill, Ernie; Bayat, Ardeshir

    2015-06-01

    Reproducing extracellular matrix topographical cues, such as those present within acellular dermal matrix (ADM), in synthetic implant surfaces, may augment cellular responses, independent of surface chemistry. This could lead to enhanced implant integration and performance while reducing complications. In this work, the hierarchical micro and nanoscale features of ADM were accurately and reproducibly replicated in polydimethylsiloxane (PDMS), using an innovative maskless 3D grayscale fabrication process not previously reported. Human breast derived fibroblasts (n=5) were cultured on PDMS surfaces and compared to commercially available smooth and textured silicone implant surfaces, for up to one week. Cell attachment, proliferation and cytotoxicity, in addition to immunofluorescence staining, SEM imaging, qRT-PCR and cytokine array were performed. ADM PDMS surfaces promoted cell adhesion, proliferation and survival (p=<0.05), in addition to increased focal contact formation and spread fibroblast morphology when compared to commercially available implant surfaces. PCNA, vinculin and collagen 1 were up-regulated in fibroblasts on biomimetic surfaces while IL8, TNFα, TGFβ1 and HSP60 were down-regulated (p=<0.05). A reduced inflammatory cytokine response was also observed (p=<0.05). This study represents a novel approach to the development of functionalised biomimetic prosthetic implant surfaces which were demonstrated to significantly attenuate the acute in vitro foreign body reaction to silicone. PMID:25818416

  18. Immunological response to re-infections with clones of the Colombian strain of Trypanosoma cruzi with different degrees of virulence: influence on pathological features during chronic infection in mice

    PubMed Central

    Guerreiro, Marcos Lazaro da Silva; Morais, Isa Rita Brito; Andrade, Sonia Gumes

    2015-01-01

    Re-infections with Trypanosoma cruzi are an aggravating factor for Chagas disease morbidity. The Colombian strain of T. cruzi represents multiclonal populations formed by clonally propagating organisms with different tropisms and degrees of virulence. In the present study, the influence of successive inoculations with clones of the Colombian strain, exhibiting different degrees of virulence, on chronic myocarditis and the humoral and cellular immune responses (Col-C1 high virulence, Col-C8 medium virulence and Col-C5 low virulence) were demonstrated. Mice from three groups with a single infection were evaluated during the acute (14th-30th day) and chronic phases for 175 days. An immunofluorescence assay, ELISA and delayed type hypersensitivity (DTH) cutaneous test were also performed. Mice with a triple infection were studied on the 115th-175th days following first inoculation. The levels of IgM and IgG2a were higher in the animals with a triple infection. DTH showed a higher intensity in the inflammatory infiltrate based on the morphometric analysis during a 48 h period of the triple infection and at 24 h with a single infection. The histopathology of the heart demonstrated significant exacerbation of cardiac inflammatory lesions confirmed by the morphometric test. The humoral responses indicate a reaction to the triple infection, even with clones of the same strain. PMID:25946153

  19. Immunological response to re-infections with clones of the Colombian strain of Trypanosoma cruzi with different degrees of virulence: influence on pathological features during chronic infection in mice.

    PubMed

    Guerreiro, Marcos Lazaro da Silva; Morais, Isa Rita Brito; Andrade, Sonia Gumes

    2015-06-01

    Re-infections with Trypanosoma cruzi are an aggravating factor for Chagas disease morbidity. The Colombian strain of T. cruzi represents multiclonal populations formed by clonally propagating organisms with different tropisms and degrees of virulence. In the present study, the influence of successive inoculations with clones of the Colombian strain, exhibiting different degrees of virulence, on chronic myocarditis and the humoral and cellular immune responses (Col-C1 high virulence, Col-C8 medium virulence and Col-C5 low virulence) were demonstrated. Mice from three groups with a single infection were evaluated during the acute (14th-30th day) and chronic phases for 175 days. An immunofluorescence assay, ELISA and delayed type hypersensitivity (DTH) cutaneous test were also performed. Mice with a triple infection were studied on the 115th-175th days following first inoculation. The levels of IgM and IgG2a were higher in the animals with a triple infection. DTH showed a higher intensity in the inflammatory infiltrate based on the morphometric analysis during a 48 h period of the triple infection and at 24 h with a single infection. The histopathology of the heart demonstrated significant exacerbation of cardiac inflammatory lesions confirmed by the morphometric test. The humoral responses indicate a reaction to the triple infection, even with clones of the same strain. PMID:25946153

  20. Immunological response to re-infections with clones of the Colombian strain of Trypanosoma cruzi with different degrees of virulence: influence on pathological features during chronic infection in mice.

    PubMed

    Guerreiro, Marcos Lazaro da Silva; Morais, Isa Rita Brito; Andrade, Sonia Gumes

    2015-06-01

    Re-infections with Trypanosoma cruzi are an aggravating factor for Chagas disease morbidity. The Colombian strain of T. cruzi represents multiclonal populations formed by clonally propagating organisms with different tropisms and degrees of virulence. In the present study, the influence of successive inoculations with clones of the Colombian strain, exhibiting different degrees of virulence, on chronic myocarditis and the humoral and cellular immune responses (Col-C1 high virulence, Col-C8 medium virulence and Col-C5 low virulence) were demonstrated. Mice from three groups with a single infection were evaluated during the acute (14th-30th day) and chronic phases for 175 days. An immunofluorescence assay, ELISA and delayed type hypersensitivity (DTH) cutaneous test were also performed. Mice with a triple infection were studied on the 115th-175th days following first inoculation. The levels of IgM and IgG2a were higher in the animals with a triple infection. DTH showed a higher intensity in the inflammatory infiltrate based on the morphometric analysis during a 48 h period of the triple infection and at 24 h with a single infection. The histopathology of the heart demonstrated significant exacerbation of cardiac inflammatory lesions confirmed by the morphometric test. The humoral responses indicate a reaction to the triple infection, even with clones of the same strain.

  1. GASIS demonstration

    SciTech Connect

    Vidas, E.H.

    1995-04-01

    A prototype of the GASIS database and retrieval software has been developed and is the subject of this poster session and computer demonstration. The prototype consists of test or preliminary versions of the GASIS Reservoir Data System and Source Directory datasets and the software for query and retrieval. The prototype reservoir database covers the Rocky Mountain region and contains the full GASIS data matrix (all GASIS data elements) that will eventually be included on the CD-ROM. It is populated for development purposes primarily by the information included in the Rocky Mountain Gas Atlas. The software has been developed specifically for GASIS using Foxpro for Windows. The application is an executable file that does not require Foxpro to run. The reservoir database software includes query and retrieval, screen display, report generation, and data export functions. Basic queries by state, basin, or field name will be assisted by scrolling selection lists. A detailed query screen will allow record selection on the basis of any data field, such as depth, cumulative production, or geological age. Logical operators can be applied to any-numeric data element or combination of elements. Screen display includes a {open_quotes}browse{close_quotes} display with one record per row and a detailed single record display. Datasets can be exported in standard formats for manipulation with other software packages. The Source Directory software will allow record retrieval by database type or subject area.

  2. Of Mice and Dogs

    PubMed Central

    Dewald, Oliver; Ren, Guofeng; Duerr, Georg D.; Zoerlein, Martin; Klemm, Christina; Gersch, Christine; Tincey, Sophia; Michael, Lloyd H.; Entman, Mark L.; Frangogiannis, Nikolaos G.

    2004-01-01

    Large animal models have provided much of the descriptive data regarding the cellular and molecular events in myocardial infarction and repair. The availability of genetically altered mice may provide a valuable tool for specific cellular and molecular dissection of these processes. In this report we compare closed chest models of canine and mouse infarction/reperfusion qualitatively and quantitatively for temporal, cellular, and spatial differences. Much like the canine model, reperfused mouse hearts are associated with marked induction of endothelial adhesion molecules, cytokines, and chemokines. Reperfused mouse infarcts show accelerated replacement of cardiomyocytes by granulation tissue leading to a thin mature scar at 14 days, when the canine infarction is still cellular and evolving. Infarcted mouse hearts demonstrate a robust but transient postreperfusion inflammatory reaction, associated with a rapid up-regulation of interleukin-10 and transforming growth factor-β. Unlike canine infarcts, infarcted mouse hearts show only transient macrophage infiltration and no significant mast cell accumulation. In correlation, the growth factor for macrophages, M-CSF, shows modest and transient up-regulation in the early days of reperfusion; and the obligate growth factor for mast cells, stem cell factor, SCF, is not induced. In summary, the postinfarction inflammatory response and resultant repair in the mouse heart shares many common characteristics with large mammalian species, but has distinct temporal and qualitative features. These important species-specific differences should be considered when interpreting findings derived from studies using genetically altered mice. PMID:14742270

  3. A complex dietary supplement extends longevity of mice.

    PubMed

    Lemon, Jennifer A; Boreham, Douglas R; Rollo, C David

    2005-03-01

    Key factors implicated in aging include reactive oxygen species, inflammatory processes, insulin resistance, and mitochondrial dysfunction. All are exaggerated in transgenic growth hormone mice (TGM), which display a syndrome resembling accelerated aging. We formulated a complex dietary supplement containing 31 ingredients known to ameliorate all of the above features. We previously showed that this supplement completely abolished the severe age-related cognitive decline expressed by untreated TGM. Here we report that longevity of both TGM and normal mice is extended by this supplement. Treated TGM showed a 28% increase (p < .00008) in mean longevity. An 11% increase in mean longevity was also significant (p < .002093) for treated normal mice, compared to untreated normal mice. These data support the hypothesis that TGM are a model of accelerated aging, and demonstrate that complex dietary supplements may be effective in ameliorating aging or age-related pathologies where simpler formulations have generally failed.

  4. An inbred line of transgenic mice expressing an internally deleted gene for type II procollagen (COL2A1). Young mice have a variable phenotype of a chondrodysplasia and older mice have osteoarthritic changes in joints.

    PubMed Central

    Helminen, H J; Kiraly, K; Pelttari, A; Tammi, M I; Vandenberg, P; Pereira, R; Dhulipala, R; Khillan, J S; Ala-Kokko, L; Hume, E L

    1993-01-01

    Studies were carried out on a line of transgenic mice that expressed an internally deleted COL2A1 gene and developed a phenotype resembling human chondrodysplasias (Vandenberg et al. 1991. Proc. Natl. Acad. Sci. USA. 88:7640-7644. Marked differences in phenotype were observed with propagation of the mutated gene in an inbred strain of mice in that approximately 15% of the transgenic mice had a cleft palate and a lethal phenotype, whereas the remaining mice were difficult to distinguish from normal littermates. 1-d- and 3-mo-old transgenic mice that were viable showed microscopic signs of chondrodysplasia with reduced amounts of collagen fibrils in the cartilage matrix, dilatation of the rough surfaced endoplasmic reticulum in the chondrocytes, and decrease of optical path difference in polarized light microscopy. The transgenic mice also showed signs of disturbed growth as evidenced by lower body weight, lower length and weight of the femur, decreased bone collagen, decreased bone mineral, and decreased resistance of bone to breakage. Comparisons of mice ranging in age from 1 d to 15 mo demonstrated that there was decreasing evidence of a chondrodysplasia as the mice grew older. Instead, the most striking feature in the 15-mo-old mice were degenerative changes of articular cartilage similar to osteoarthritis. Images PMID:8349798

  5. Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice.

    PubMed

    Soenjaya, Y; Foster, B L; Nociti, F H; Ao, M; Holdsworth, D W; Hunter, G K; Somerman, M J; Goldberg, H A

    2015-09-01

    Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp(-/-)) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp(-/-) mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp(-/-) mice. This hypothesis was tested by comparing Bsp(-/-) and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro-computed tomography. By 8 wk of age, Bsp(-/-) mice exhibited molar and incisor malocclusion regardless of diet. Bsp(-/-) mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp(-/-) mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp(-/-) mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp(-/-) mice. Bsp(-/-) incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the

  6. Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice

    PubMed Central

    Soenjaya, Y.; Foster, B.L.; Nociti, F.H.; Ao, M.; Holdsworth, D.W.; Hunter, G.K.; Somerman, M.J.

    2015-01-01

    Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp-/-) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp-/- mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp-/- mice. This hypothesis was tested by comparing Bsp-/- and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro–computed tomography. By 8 wk of age, Bsp-/- mice exhibited molar and incisor malocclusion regardless of diet. Bsp-/- mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp-/- mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp-/- mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp-/- mice. Bsp-/- incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the importance of BSP

  7. Dealer model site demonstrations

    SciTech Connect

    Mann, H.C.

    1992-08-01

    Model site demonstrations are joint efforts between TVA and cooperating organizations to improve the industry's environmental stewardship. Program objectives are to develop, demonstrate, and transfer technologies and management practices to help retail fertilizer/agricultural chemical dealers minimize adverse environmental impacts. The model site demonstrations serve as 'real life' laboratories for researchers, technologists, educators and participants. The retail dealership is treated as a complete unit. The program recognizes the need to: Develop information and experience to guide others; Test numerous methods of containment, materials of construction, management practices, and monitoring techniques; Strengthen and highlight industry's commitment to envirorunental stewardship; Identify future research needs; and Provide a catalyst for cooperation across a broad spectrum of groups and organizations to identify problems and develop solutions appropriate for fertilizer and agrichemical dealers. Emphasis is on transferring current technology and developing and introducing needed new technologies. Field testing and applied research are encouraged at demonstration sites. One of the key concepts is to bridge the gap between research findings and their practical application and evaluation in field settings. Primary audiences include fertilizer dealers and professional workers in agriculture, the fertilizer industry, the environmental arena, and related institutions across the nation. Experiences at participating dealer sites are shared through organized tours, open houses, news articles and publications. Sixteen sites have been selected for demonstrations, and at least four more are planned. TVA provides assistance in engineering, design and educational forums. Dealers pay for installation of needed containment and related features.

  8. [Experimental infection caused by Machupo virus in intact and immunosuppressed albino mice].

    PubMed

    Orlova, S V; Votiakov, V I

    1989-01-01

    Features of the course of experimental infection in white mice caused by Machupo virus in relation to their age, route of virus inoculation, and under conditions of normal and suppressed immune response created by antithymocyte globulin (ATG) were studied. The effect of different ATG doses and intervals of its administration on the experimental infection were demonstrated.

  9. Immunopathogenesis of environmentally induced lupus in mice.

    PubMed Central

    Shaheen, V M; Satoh, M; Richards, H B; Yoshida, H; Shaw, M; Jennette, J C; Reeves, W H

    1999-01-01

    Systemic lupus erythematosus (SLE) is a systemic autoimmune syndrome defined by clinical and serologic features, including arthritis, glomerulonephritis, and certain autoantibodies such as anti-nuclear ribonucleoprotein (nRNP)/Smith antigen (Sm), DNA, and ribosomal P. Although lupus is considered primarily a genetic disorder, we recently demonstrated the induction of a syndrome strikingly similar to spontaneous lupus in many nonautoimmune strains of mice exposed to the isoprenoid alkane pristane (2,6,10,14-tetramethylpentadecane), a component of mineral oil. Intraperitoneal injection of pristane leads to the formation of lipogranulomas consisting of phagocytic cells that have engulfed the oil and collections of lymphocytes. Subsequently, pristane-treated BALB/c and SJL mice develop autoantibodies characteristic of SLE, including anti-nRNP/Sm, antiribosomal P, anti-Su, antichromatin, anti-single-stranded DNA, and anti-double-stranded DNA. This is accompanied by a severe glomerulonephritis with immune complex deposition, mesangial or mesangiocapillary proliferation, and proteinuria. All inbred mice examined appear to be susceptible to this novel form of chemically induced lupus. Pristane-induced lupus is the only inducible model of autoimmunity associated with the clinical syndrome as well as with the characteristic serologic abnormalities of SLE. Defining the immunopathogenesis of pristane-induced lupus in mice may provide insight into the causes of spontaneous (idiopathic) lupus and also may lead to information concerning possible risks associated with the ingestion or inhalation of mineral oil and exposure to hydrocarbons in the environment. Images Figure 1 Figure 2 Figure 3 PMID:10502537

  10. Partial Return Yoke for MICE

    SciTech Connect

    Witte H.; Plate, S

    2013-05-03

    The international Muon Ionization Cooling Experiment (MICE) is a large scale experiment which is presently assembled at the Rutherford Appleton Laboratory in Didcot, UK. The purpose of MICE is to demonstrate the concept of ionization cooling experimentally. Ionization cooling is an important accelerator concept which will be essential for future HEP experiments such as a potential Muon Collider or a Neutrino Factory. The MICE experiment will house up to 18 superconducting solenoids, all of which produce a substantial amount of magnetic flux. Recently it was realized that this magnetic flux leads to a considerable stray magnetic field in the MICE hall. This is a concern as technical equipment in the MICE hall may may be compromised by this. In July 2012 a concept called partial return yoke was presented to the MICE community, which reduces the stray field in the MICE hall to a safe level. This report summarizes the general concept, engineering considerations and the expected shielding performance.

  11. Intracellular demonstration of active TGFbeta1 in B cells and plasma cells of autoimmune mice. IgG-bound TGFbeta1 suppresses neutrophil function and host defense against Staphylococcus aureus infection.

    PubMed Central

    Caver, T E; O'Sullivan, F X; Gold, L I; Gresham, H D

    1996-01-01

    Infection remains a leading cause of morbidity and mortality in patients with SLE. To investigate this, previously we assessed the host defense status of autoimmune MRL/lpr mice and found that elaboration of active TGFbeta suppressed neutrophil function and decreased survival in response to Staphylococcus aureus infection. The purpose of the present work was to elucidate the molecular form and the cellular source of the active TGFbeta involved. Here, we report for the first time that TGFbeta1 is found in the active form inside B cells and plasma cells and that it circulates in the plasma complexed with IgG in two murine models of systemic autoimmunity and in some patients with SLE. IgG-bound active TGFbeta1 is many times more potent than uncomplexed active TGFbeta1 for suppression of neutrophil function in vitro and host defense against S. aureus infection in vivo. These data indicate that TGFbeta1 is in the active form inside B cells and plasma cells, that the formation of a complex of IgG and active TGFbeta1 is greatly accelerated in autoimmunity, and that this complex is extremely potent for suppression of PMN function and host defense against bacterial infection. PMID:8958212

  12. Demonstrational Features of the Tuskegee Institute Retraining Project, Volume I.

    ERIC Educational Resources Information Center

    Tuskegee Inst., AL.

    This 52-week Tuskegee Institute project, undertaken in 1964 to train a sample of culturally deprived male heads of households in Alabama, included vocational skills (brickmasonry, carpentry, farm machinery, and meat processing), academic skills (mathematics, English, and remedial reading), group, individual, and family counseling, medical care,…

  13. Lack of Chronic Histologic Lesions Supportive of Sublethal Spontaneous Seizures in FVB/N Mice.

    PubMed

    Kohnken, Rebecca A; Schwahn, Denise J

    2016-04-01

    FVB/N mice with 'space cadet' syndrome are prone to audiogenic seizures and are considered excitotoxic 'sensitive' mice due to the neuronal damage that accompanies seizures. FVB/N mice found dead demonstrate acute neuronal cell death--attributed to a massive seizure episode--within the hippocampus and cerebrocortical laminae. However, the behavioral features of FVB/N mice and numerous studies using excitotoxins to induce seizure activity indicate that this strain experiences multiple sublethal seizures. To assess whether FVB/N mice develop histologically detectable lesions, we evaluated the brains of 86 aged (154-847 d) FVB/N mice without a history of seizures. The hippocampus and cerebrocortical laminae were evaluated histologically for neuronal atrophy and gliosis. Neuronal atrophy was quantified by counting neurons in the hippocampus (CA3 and dentate gyrus) and cerebral cortex. Gliosis was quantified by using immunohistochemistry for glial fibrillary acidic protein and glial counting in the cerebral cortex. In addition, ventricular area was calculated. Our study revealed no changes in brain weight with age, no neuronal loss or gliosis, no correlation between neuronal or glial cell profile densities and brain weight or age, and no differences in ventricular size between FVB/N and control mice. Neuronal densities in the cerebral cortex and granule cells of the dentate gyrus were lower in FVB/N mice than in control Swiss Webster mice. We conclude that although acute lesions of seizure activity are a previous feature of the FVB/N strain, chronic seizure activity in these mice either is negligible or does not cause morphologic or phenotypic changes.

  14. Lack of Chronic Histologic Lesions Supportive of Sublethal Spontaneous Seizures in FVB/N Mice

    PubMed Central

    Kohnken, Rebecca A; Schwahn, Denise J

    2016-01-01

    FVB/N mice with ‘space cadet’ syndrome are prone to audiogenic seizures and are considered excitotoxic ‘sensitive’ mice due to the neuronal damage that accompanies seizures. FVB/N mice found dead demonstrate acute neuronal cell death—attributed to a massive seizure episode—within the hippocampus and cerebrocortical laminae. However, the behavioral features of FVB/N mice and numerous studies using excitotoxins to induce seizure activity indicate that this strain experiences multiple sublethal seizures. To assess whether FVB/N mice develop histologically detectable lesions, we evaluated the brains of 86 aged (154-847 d) FVB/N mice without a history of seizures. The hippocampus and cerebrocortical laminae were evaluated histologically for neuronal atrophy and gliosis. Neuronal atrophy was quantified by counting neurons in the hippocampus (CA3 and dentate gyrus) and cerebral cortex. Gliosis was quantified by using immunohistochemistry for glial fibrillary acidic protein and glial counting in the cerebral cortex. In addition, ventricular area was calculated. Our study revealed no changes in brain weight with age, no neuronal loss or gliosis, no correlation between neuronal or glial cell profile densities and brain weight or age, and no differences in ventricular size between FVB/N and control mice. Neuronal densities in the cerebral cortex and granule cells of the dentate gyrus were lower in FVB/N mice than in control Swiss Webster mice. We conclude that although acute lesions of seizure activity are a previous feature of the FVB/N strain, chronic seizure activity in these mice either is negligible or does not cause morphologic or phenotypic changes. PMID:27053564

  15. Feature selection in bioinformatics

    NASA Astrophysics Data System (ADS)

    Wang, Lipo

    2012-06-01

    In bioinformatics, there are often a large number of input features. For example, there are millions of single nucleotide polymorphisms (SNPs) that are genetic variations which determine the dierence between any two unrelated individuals. In microarrays, thousands of genes can be proled in each test. It is important to nd out which input features (e.g., SNPs or genes) are useful in classication of a certain group of people or diagnosis of a given disease. In this paper, we investigate some powerful feature selection techniques and apply them to problems in bioinformatics. We are able to identify a very small number of input features sucient for tasks at hand and we demonstrate this with some real-world data.

  16. General features

    SciTech Connect

    Wallace, R.E.

    1990-01-01

    The San Andreas fault system, a complex of faults that display predominantly large-scale strike slip, is part of an even more complex system of faults, isolated segments of the East Pacific Rise, and scraps of plates lying east of the East Pacific Rise that collectively separate the North American plate from the Pacific plate. This chapter briefly describes the San Andreas fault system, its setting along the Pacific Ocean margin of North America, its extent, and the patterns of faulting. Only selected characteristics are described, and many features are left for depictions on maps and figures.

  17. Automatic Visual Tracking and Social Behaviour Analysis with Multiple Mice

    PubMed Central

    Giancardo, Luca; Sona, Diego; Huang, Huiping; Sannino, Sara; Managò, Francesca; Scheggia, Diego; Papaleo, Francesco; Murino, Vittorio

    2013-01-01

    Social interactions are made of complex behavioural actions that might be found in all mammalians, including humans and rodents. Recently, mouse models are increasingly being used in preclinical research to understand the biological basis of social-related pathologies or abnormalities. However, reliable and flexible automatic systems able to precisely quantify social behavioural interactions of multiple mice are still missing. Here, we present a system built on two components. A module able to accurately track the position of multiple interacting mice from videos, regardless of their fur colour or light settings, and a module that automatically characterise social and non-social behaviours. The behavioural analysis is obtained by deriving a new set of specialised spatio-temporal features from the tracker output. These features are further employed by a learning-by-example classifier, which predicts for each frame and for each mouse in the cage one of the behaviours learnt from the examples given by the experimenters. The system is validated on an extensive set of experimental trials involving multiple mice in an open arena. In a first evaluation we compare the classifier output with the independent evaluation of two human graders, obtaining comparable results. Then, we show the applicability of our technique to multiple mice settings, using up to four interacting mice. The system is also compared with a solution recently proposed in the literature that, similarly to us, addresses the problem with a learning-by-examples approach. Finally, we further validated our automatic system to differentiate between C57B/6J (a commonly used reference inbred strain) and BTBR T+tf/J (a mouse model for autism spectrum disorders). Overall, these data demonstrate the validity and effectiveness of this new machine learning system in the detection of social and non-social behaviours in multiple (>2) interacting mice, and its versatility to deal with different experimental settings and

  18. A Fluorescence Lecture Demonstration.

    ERIC Educational Resources Information Center

    Bozzelli, Joseph W.; Kemp, Marwin

    1982-01-01

    Describes fluorescence demonstrations related to several aspects of molecular theory and quantitized energy levels. Demonstrations use fluorescent chemical solutions having luminescence properties spanning the visible spectrum. Also describes a demonstration of spontaneous combustion of familiar substances in chlorine. (JN)

  19. ORION II bus demonstration. Demonstration report (Final)

    SciTech Connect

    Shanley, J.

    1989-02-01

    The Central New York Regional Transportation Authority conducted an 18-month demonstration to determine how the ORION II bus operates in actual service. The ORION II vehicle is a small low floor, accessible heavy duty, diesel-powered transit bus designed to meet the needs of the elderly and handicapped. It has the capacity to seat 26 passengers with 4 wheelchair lockdowns. Side and rear doors are equipped with electrically powered ramps. Eight Thomas vehicles (22-foot, 11,500 lbs, wheelchair equipped, gasoline fueled) were also tested during the demonstration period. Operations (fuel and oil usage) and maintenance (scheduled and unscheduled) data were collected and charted-out in the report as well as driver, passenger, and maintenance surveys. This report provides descriptions, photographs, and comparison charts of both the diesel-fueled ORION II transit bus and the gasoline-fueled Thomas vehicles along with the demonstration test plan, evaluations, conclusions, and survey results.

  20. Self-Tracking Energy Transfer for Neural Stimulation in Untethered Mice

    NASA Astrophysics Data System (ADS)

    Ho, John S.; Tanabe, Yuji; Iyer, Shrivats Mohan; Christensen, Amelia J.; Grosenick, Logan; Deisseroth, Karl; Delp, Scott L.; Poon, Ada S. Y.

    2015-08-01

    Optical or electrical stimulation of neural circuits in mice during natural behavior is an important paradigm for studying brain function. Conventional systems for optogenetics and electrical microstimulation require tethers or large head-mounted devices that disrupt animal behavior. We report a method for wireless powering of small-scale implanted devices based on the strong localization of energy that occurs during resonant interaction between a radio-frequency cavity and intrinsic modes in mice. The system features self-tracking over a wide (16-cm diameter) operational area, and is used to demonstrate wireless activation of cortical neurons with miniaturized stimulators (10 mm3 , 20 mg) fully implanted under the skin.

  1. Herschel's Interference Demonstration.

    ERIC Educational Resources Information Center

    Perkalskis, Benjamin S.; Freeman, J. Reuben

    2000-01-01

    Describes Herschel's demonstration of interference arising from many coherent rays. Presents a method for students to reproduce this demonstration and obtain beautiful multiple-beam interference patterns. (CCM)

  2. Restoration of lymphatic function rescues obesity in Prox1-haploinsufficient mice

    PubMed Central

    Proulx, Steven T.; Dillard, Miriam E.; Johnson, Nicole; Detmar, Michael

    2016-01-01

    Prox1 heterozygous mice have a defective lymphatic vasculature and develop late-onset obesity. Chyle abnormally leaks from those vessels, accumulates in the surrounding tissues, and causes an increase in adipose tissue. We characterized the lymphatics of Prox1+/– mice to determine whether the extent of obesity correlated with the severity of lymphatic defects. The lymphatic vasculature in Prox1+/– mice exhibited reduced tracer clearance from the ear skin, dysfunctional perfusion of the lower legs, and reduced tracer uptake into the deep lymphatic collectors during mechanostimulation prior to the onset of obesity. Ear lymphatic vessels and leg collectors in Prox1+/– mice were disorganized and irregular, further confirming that defective lymphatic vessels are associated with obesity in Prox1+/– mice. We now provide conclusive in vivo evidence that demonstrates that leaky lymphatics mediate obesity in Prox1+/– mice, as restoration of lymphatic vasculature function was sufficient to rescue the obesity features in Prox1+/– mice. Finally, depth-lipomic profiling of lymph contents showed that free fatty acids induce adipogenesis in vitro. PMID:26973883

  3. Porphyromonas gingivalis Accelerates Inflammatory Atherosclerosis in the Innominate Artery of ApoE Deficient Mice

    PubMed Central

    Hayashi, Chie; Viereck, Jason; Hua, Ning; Phinikaridou, Alkystis; Madrigal, Andres G.; Gibson, Frank C.; Hamilton, James A.; Genco, Caroline A.

    2011-01-01

    Objective Studies in humans support a role for the oral pathogen Porphyromonas gingivalis in the development of inflammatory atherosclerosis. The goal of this study was to determine if P. gingivalis infection accelerates inflammation and atherosclerosis in the innominate artery of mice, an artery which has been reported to exhibit many features of human atherosclerotic disease, including plaque rupture. Methods and Results Apolipoprotein E-deficient (ApoE−/−) mice were orally infected with P. gingivalis, and Magnetic Resonance Imaging (MRI) was used to monitor the progression of atherosclerosis in live mice. P. gingivalis infected mice exhibited a statistically significant increase in atherosclerotic plaque in the innominate artery as compared to uninfected mice. Polarized light microscopy and immunohistochemistry revealed that the innominate arteries of infected mice had increased lipids, macrophages and T cells as compared to uninfected mice. Increases in plaque, total cholesterol esters and cholesterol monohydrate crystals, macrophages, and T cells were prevented by immunization with heat-killed P. gingivalis prior to pathogen exposure. Conclusions These are the first studies to demonstrate progression of inflammatory plaque accumulation in the innominate arteries by in-vivo MRI analysis following pathogen exposure, and to document protection from plaque progression in the innominate artery via immunization. PMID:21251656

  4. Ovariectomy is associated with metabolic impairments and enhanced mammary tumor growth in MKR mice.

    PubMed

    Ben-Shmuel, Sarit; Scheinman, Eyal J; Rashed, Rola; Orr, Zila Shen; Gallagher, Emily J; LeRoith, Derek; Rostoker, Ran

    2015-12-01

    Obesity and type 2 diabetes (T2D) are associated with an increased risk of breast cancer incidence and mortality. Common features of obesity and T2D are insulin resistance and hyperinsulinemia. A mammary tumor promoting effect of insulin resistance and hyperinsulinemia was demonstrated in the transgenic female MKR mouse model of pre-diabetes inoculated with mammary cancer cells. Interestingly, in MKR mice, as well as in other diabetic mouse models, males exhibit severe hyperglycemia, while females display insulin resistance and hyperinsulinemia with only a mild increase in blood glucose levels. This gender-specific protection from hyperglycemia may be attributed to estradiol, a key player in the regulation of the metabolic state, including obesity, glucose homeostasis, insulin resistance, and lipid profile. The aim of this study was to investigate the effects of ovariectomy (including the removal of endogenous estradiol) on the metabolic state of MKR female mice and subsequently on the growth of Mvt-1 mammary cancer cells, inoculated into the mammary fat pad of ovariectomized mice, compared with sham-operated mice. The results showed an increase in body weight, accompanied by increased fat mass, elevated blood glucose levels, and hypercholesterolemia, in ovariectomized MKR mice. In addition, mammary tumor growth was significantly higher in these mice. The results suggest that ovarian hormone deficiency may promote impaired metabolic homeostasis in the hyperinsulinemic MKR female mice, which in turn is associated with an increased growth of mammary tumors. PMID:26383532

  5. No obvious abnormality in mice deficient in receptor protein tyrosine phosphatase beta.

    PubMed

    Harroch, S; Palmeri, M; Rosenbluth, J; Custer, A; Okigaki, M; Shrager, P; Blum, M; Buxbaum, J D; Schlessinger, J

    2000-10-01

    The development of neurons and glia is governed by a multitude of extracellular signals that control protein tyrosine phosphorylation, a process regulated by the action of protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Receptor PTPbeta (RPTPbeta; also known as PTPzeta) is expressed predominantly in the nervous system and exhibits structural features common to cell adhesion proteins, suggesting that this phosphatase participates in cell-cell communication. It has been proposed that the three isoforms of RPTPbeta play a role in regulation of neuronal migration, neurite outgrowth, and gliogenesis. To investigate the biological functions of this PTP, we have generated mice deficient in RPTPbeta. RPTPbeta-deficient mice are viable, are fertile, and showed no gross anatomical alterations in the nervous system or other organs. In contrast to results of in vitro experiments, our study demonstrates that RPTPbeta is not essential for neurite outgrowth and node formation in mice. The ultrastructure of nerves of the central nervous system in RPTPbeta-deficient mice suggests a fragility of myelin. However, conduction velocity was not altered in RPTPbeta-deficient mice. The normal development of neurons and glia in RPTPbeta-deficient mice demonstrates that RPTPbeta function is not necessary for these processes in vivo or that loss of RPTPbeta can be compensated for by other PTPs expressed in the nervous system. PMID:11003666

  6. Why Demonstrations Matter

    ERIC Educational Resources Information Center

    Black, Richard

    2005-01-01

    With the current focus on constructivist perspectives, science demonstrations have fallen out of favor in some circles. Demonstrations are easy to do and offer many benefits and unique opportunities in the constructivist classroom. With careful use, demonstrations can be powerful teaching tools. A wonderful quality of a demonstration (or a series…

  7. Mice with human livers.

    PubMed

    Grompe, Markus; Strom, Stephen

    2013-12-01

    Animal models are used to study many aspects of human disease and to test therapeutic interventions. However, some very important features of human biology cannot be replicated in animals, even in nonhuman primates or transgenic rodents engineered with human genes. Most human microbial pathogens do not infect animals and the metabolism of many xenobiotics is different between human beings and animals. The advent of transgenic immune-deficient mice has made it possible to generate chimeric animals harboring human tissues and cells, including hepatocytes. The liver plays a central role in many human-specific biological processes and mice with humanized livers can be used to model human metabolism, liver injury, gene regulation, drug toxicity, and hepatotropic infections.

  8. Image feature localization by multiple hypothesis testing of Gabor features.

    PubMed

    Ilonen, Jarmo; Kamarainen, Joni-Kristian; Paalanen, Pekka; Hamouz, Miroslav; Kittler, Josef; Kälviäinen, Heikki

    2008-03-01

    Several novel and particularly successful object and object category detection and recognition methods based on image features, local descriptions of object appearance, have recently been proposed. The methods are based on a localization of image features and a spatial constellation search over the localized features. The accuracy and reliability of the methods depend on the success of both tasks: image feature localization and spatial constellation model search. In this paper, we present an improved algorithm for image feature localization. The method is based on complex-valued multi resolution Gabor features and their ranking using multiple hypothesis testing. The algorithm provides very accurate local image features over arbitrary scale and rotation. We discuss in detail issues such as selection of filter parameters, confidence measure, and the magnitude versus complex representation, and show on a large test sample how these influence the performance. The versatility and accuracy of the method is demonstrated on two profoundly different challenging problems (faces and license plates).

  9. The MICE Muon Beam Line

    NASA Astrophysics Data System (ADS)

    Apollonio, Marco

    2011-10-01

    In the Muon Ionization Cooling Experiment (MICE) at RAL, muons are produced and transported in a dedicated beam line connecting the production point (target) to the cooling channel. We discuss the main features of the beamline, meant to provide muons with momenta between 140 MeV/c and 240 MeV/c and emittances up to 10 mm rad, which is accomplished by means of a diffuser. Matching procedures to the MICE cooling channel are also described. In summer 2010 we performed an intense data taking campaign to finalize the calibration of the MICE Particle Identification (PID) detectors and the understanding of the beam line, which completes the STEPI phase of MICE. We highlight the main results from these data.

  10. LIMB Demonstration Project Extension and Coolside Demonstration

    SciTech Connect

    Goots, T.R.; DePero, M.J.; Nolan, P.S.

    1992-11-10

    This report presents results from the limestone Injection Multistage Burner (LIMB) Demonstration Project Extension. LIMB is a furnace sorbent injection technology designed for the reduction of sulfur dioxide (SO[sub 2]) and nitrogen oxides (NO[sub x]) emissions from coal-fired utility boilers. The testing was conducted on the 105 Mwe, coal-fired, Unit 4 boiler at Ohio Edison's Edgewater Station in Lorain, Ohio. In addition to the LIMB Extension activities, the overall project included demonstration of the Coolside process for S0[sub 2] removal for which a separate report has been issued. The primary purpose of the DOE LIMB Extension testing, was to demonstrate the generic applicability of LIMB technology. The program sought to characterize the S0[sub 2] emissions that result when various calcium-based sorbents are injected into the furnace, while burning coals having sulfur content ranging from 1.6 to 3.8 weight percent. The four sorbents used included calcitic limestone, dolomitic hydrated lime, calcitic hydrated lime, and calcitic hydrated lime with a small amount of added calcium lignosulfonate. The results include those obtained for the various coal/sorbent combinations and the effects of the LIMB process on boiler and plant operations.

  11. Report on modular hydropower demonstration

    SciTech Connect

    Pelton, F.

    1988-09-01

    This report describes an Energy Authority project to demonstrate the use of modular small hydropower systems at two sites. The project demonstrated that 'off-the-shelf' components can be used to construct a functionally reliable, cost-effective hydropower system at a significant savings over custom-designed systems. A key feature of the modular system is the replacement of the conventional hydroelectric turbine with a pump operated in reverse. Also, the construction of a water-intake system in the dam is replaced with a siphon penstock. Further cost and time savings are gained from the use of a prefabricated powerhouse and automated control equipment. The project demonstrated that modular systems are an attractive option for sites with capacities from under 100 to 500 kilowatts. The modular concept is applicable at about 250 sites Statewide, with a combined capacity of up to 400 MW.

  12. Laithwaite's Heavy Spinning Disk Demonstration

    NASA Astrophysics Data System (ADS)

    Cross, Rod

    2014-09-01

    In 1974, Professor Eric Laithwaite demonstrated an unusually heavy gyroscope at a Royal Institution lecture in London. The demonstration was televised and can be viewed on YouTube.1 A recent version of the same experiment, together with partial explanations, attracted two million YouTube views in the first few months.2 In both cases, the gyroscope consisted of a 40-lb (18-kg) spinning disk on the end of a 3-ft (0.91-m) long axle. The most remarkable feature of the demonstration was that Laithwaite was able to lift the disk over his head with one hand, holding onto the far end of the axle. The impression was given that the 40-lb disk was almost weightless, or "as light as a feather" according to Laithwaite.

  13. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Kolb, Doris, Ed.

    1987-01-01

    Describes several chemistry demonstrations that use an overhead projector. Some of the demonstrations deal with electrochemistry, and another deals with the reactions of nonvolatile immiscible liquid in water. (TW)

  14. Traveling Wave Demonstration.

    ERIC Educational Resources Information Center

    Kluger-Bell, Barry

    1995-01-01

    Describes a traveling-wave demonstration that uses inexpensive materials (crepe-paper streamers) and is simple to assemble and perform. Explains how the properties of light waves are illustrated using the demonstration apparatus. (LZ)

  15. Polarized Light Corridor Demonstrations.

    ERIC Educational Resources Information Center

    Davies, G. R.

    1990-01-01

    Eleven demonstrations of light polarization are presented. Each includes a brief description of the apparatus and the effect demonstrated. Illustrated are strain patterns, reflection, scattering, the Faraday Effect, interference, double refraction, the polarizing microscope, and optical activity. (CW)

  16. Adolescents' Demonstrative Behavior Research

    ERIC Educational Resources Information Center

    Parfilova, Gulfiya G.; Karimova, Lilia Sh.

    2016-01-01

    The problem of demonstrative behavior is very topical among teenagers and this issue has become the subject of systematic scientific research. Demonstrative manifestations in adolescents disrupt the favorable socialization; therefore, understanding, prevention and correction of demonstrative behavior at this age is relevant and requires special…

  17. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Kolb, Doris, Ed.

    1988-01-01

    Details two demonstrations for use with an overhead projector in a chemistry lecture. Includes "A Very Rapidly Growing Silicate Crystal" and "A Colorful Demonstration to Simulate Orbital Hybridization." The materials and directions for each demonstration are included as well as a brief explanation of the essential learning involved. (CW)

  18. A Boyle's Law Demonstrator.

    ERIC Educational Resources Information Center

    Sathe, Dileep V.

    1984-01-01

    The usual apparatus for demonstrating Boyle's law produces reasonably accurate results, but is not impressive as a demonstration because students cannot easily appreciate the change in pressure. An apparatus designed to produce a more effective demonstration is described. Procedures employed are also described. (JN)

  19. Classroom Demonstrations: Individual Differences.

    ERIC Educational Resources Information Center

    Singer, Sandra M.

    These demonstrations stress individual differences, a concept becoming increasingly important in psychological research. Intended for use in undergraduate psychology courses, four demonstrations that illustrate common examples of human variation are described. The demonstrations deal with the following individual differences: taste blindness,…

  20. Disrupted iron homeostasis causes dopaminergic neurodegeneration in mice

    PubMed Central

    Matak, Pavle; Matak, Andrija; Moustafa, Sarah; Aryal, Dipendra K.; Benner, Eric J.; Wetsel, William; Andrews, Nancy C.

    2016-01-01

    Disrupted brain iron homeostasis is a common feature of neurodegenerative disease. To begin to understand how neuronal iron handling might be involved, we focused on dopaminergic neurons and asked how inactivation of transport proteins affected iron homeostasis in vivo in mice. Loss of the cellular iron exporter, ferroportin, had no apparent consequences. However, loss of transferrin receptor 1, involved in iron uptake, caused neuronal iron deficiency, age-progressive degeneration of a subset of dopaminergic neurons, and motor deficits. There was gradual depletion of dopaminergic projections in the striatum followed by death of dopaminergic neurons in the substantia nigra. Damaged mitochondria accumulated, and gene expression signatures indicated attempted axonal regeneration, a metabolic switch to glycolysis, oxidative stress, and the unfolded protein response. We demonstrate that loss of transferrin receptor 1, but not loss of ferroportin, can cause neurodegeneration in a subset of dopaminergic neurons in mice. PMID:26929359

  1. Disrupted iron homeostasis causes dopaminergic neurodegeneration in mice.

    PubMed

    Matak, Pavle; Matak, Andrija; Moustafa, Sarah; Aryal, Dipendra K; Benner, Eric J; Wetsel, William; Andrews, Nancy C

    2016-03-29

    Disrupted brain iron homeostasis is a common feature of neurodegenerative disease. To begin to understand how neuronal iron handling might be involved, we focused on dopaminergic neurons and asked how inactivation of transport proteins affected iron homeostasis in vivo in mice. Loss of the cellular iron exporter, ferroportin, had no apparent consequences. However, loss of transferrin receptor 1, involved in iron uptake, caused neuronal iron deficiency, age-progressive degeneration of a subset of dopaminergic neurons, and motor deficits. There was gradual depletion of dopaminergic projections in the striatum followed by death of dopaminergic neurons in the substantia nigra. Damaged mitochondria accumulated, and gene expression signatures indicated attempted axonal regeneration, a metabolic switch to glycolysis, oxidative stress, and the unfolded protein response. We demonstrate that loss of transferrin receptor 1, but not loss of ferroportin, can cause neurodegeneration in a subset of dopaminergic neurons in mice.

  2. Edible Astronomy Demonstrations

    NASA Astrophysics Data System (ADS)

    Lubowich, D. A.

    2006-08-01

    By using astronomy demonstrations with edible ingredients, I have been able to increase student interest and knowledge of astronomical concepts. This approach has been successful with all age groups from elementary school through college students. I will present some of the edible demonstrations I have created including using popcorn to simulate radioactivity; using chocolate, nuts, and marshmallows to illustrate density and differentiation during the formation of the planets; and making big-bang brownies or chocolate chip-cookies to illustrate the expansion of the Universe. Sometimes the students eat the results of the astronomical demonstrations. These demonstrations are an effective teaching tool and the students remember these demonstrations after they are presented.

  3. Strategy Guideline. Demonstration Home

    SciTech Connect

    Hunt, A.; Savage, C.

    2012-12-01

    This guideline will provide a general overview of the different kinds of demonstration home projects, a basic understanding of the different roles and responsibilities involved in the successful completion of a demonstration home, and an introduction into some of the lessons learned from actual demonstration home projects. Also, this guideline will specifically look at the communication methods employed during demonstration home projects. And lastly, we will focus on how to best create a communication plan for including an energy efficient message in a demonstration home project and carry that message to successful completion.

  4. Strategy Guideline: Demonstration Home

    SciTech Connect

    Savage, C.; Hunt, A.

    2012-12-01

    This guideline will provide a general overview of the different kinds of demonstration home projects, a basic understanding of the different roles and responsibilities involved in the successful completion of a demonstration home, and an introduction into some of the lessons learned from actual demonstration home projects. Also, this guideline will specifically look at the communication methods employed during demonstration home projects. And lastly, we will focus on how to best create a communication plan for including an energy efficient message in a demonstration home project and carry that message to successful completion.

  5. Status of MICE

    SciTech Connect

    Soler, F. J. P.

    2010-03-30

    The Muon Ionization Cooling Experiment (MICE) is an experiment currently under construction at the Rutherford Appleton Laboratory (RAL) in the UK. The aim of the experiment is to demonstrate the concept of ionization cooling for a beam of muons, crucial for the requirements of a Neutrino Factory and a Muon Collider. Muon cooling is achieved by measuring the reduction of the four dimensional transverse emittance for a beam of muons passing through low density absorbers and then accelerating the longitudinal component of the momentum using RF cavities. The absorbers are maintained in a focusing magnetic field to reduce the beta function of the beam and the RF cavities are kept inside coupling coils. The main goal of MICE is to measure a fractional drop in emittance, of order -10% for large emittance beams, with an accuracy of 1%(which imposes a requirement that the absolute emittance be measured with an accuracy of 0.1%). This paper will discuss the status of MICE, including the progress in commissioning the muon beam line at the ISIS accelerator at RAL, the construction of the different detector elements in MICE and the prospects for the future.

  6. [The aging particularities of bone marrow composition, pineal gland and thymus functions in mice of different lines].

    PubMed

    Labunets, I F

    2013-01-01

    We investigated the amount of stromal precursor cells for colonies of fibroblasts (CFC-F) and progenitor cells for granulocyte-macrophage colonies (CFC-GM cells), blood content of thymulin and melatonin in bone marrow of young and old mice CBA/Ca and FVB/N lines. The CBA/Ca mice demonstrated only weak increasing amount of CFC-F and CFC-GM in bone marrow, but these indices in FVB/N mice are increased more significantly. Linear difference of age-related changes in the biological features of the cells of bone marrow are significantly associated with the characteristics and relationships of the function of epiphysis and the thymus in mice of different lines during aging.

  7. A role for Toll-like receptor 4 in the host response to the lung infection of Yersinia pseudotuberculosis in mice.

    PubMed

    Choi, Jin-A; Jeong, Yu-Jin; Kim, Jae-Eun; Kang, Min-Jung; Kim, Jee-Cheon; Oh, Sang-Muk; Lee, Kyung-Bok; Kim, Dong-Hyun; Kim, Dong-Jae; Park, Jong-Hwan

    2016-02-01

    Although a Yersinia pseudotuberculosis (Yptb) lung infection model has been developed to study Y. pestis pathogenesis, it is still necessary to establish a new animal model to mimic the pathophysiological features induced by Y. pestis infection. Here, we provide a new lung infection model using the Yptb strain, IP2777, which displayed rapid spread of bacteria to the liver, spleen, and blood. In addition, we examined whether TLR4 is involved in Yptb-induced pathogenesis in the lung infection model of mice we generated. Following lung infection of WT and TLR4-deficient mice with the Yptb strain IP2777, the survival rate, bacterial colonization, histopathology, and level of cytokines and chemokines in the lung, spleen, liver, and blood were analyzed. TLR4-deficient mice had a lower survival rate than WT mice in response to Yptb lung infection. Although the bacterial colonization and pathology of the lung were comparable between WT and TLR4-deficient mice, those of the spleen and liver were more severe in TLR4-deficient mice. In addition, the levels of TNF-α and CXCL2 in the liver and IL-6 and CXCL2 in the blood were higher in TLR4-deficient mice than in WT mice. Our results demonstrate that TLR4 is necessary for optimal host protection against Yptb lung infection and TLR4-deficient mice may serve as a better genetic model of Yptb infection for mimicking Y. pestis infection. PMID:26851596

  8. Pulmonary eosinophils and their role in immunopathologic responses to formalin-inactivated pneumonia virus of mice

    PubMed Central

    Percopo, Caroline M.; Qiu, Zhijun; Phipps, Simon; Foster, Paul S.; Domachowske, Joseph B.; Rosenberg, Helene F.

    2009-01-01

    Enhanced disease is the term used to describe the aberrant Th2 skewed responses to naturally-acquired human respiratory syncytial virus (hRSV) infection observed in individuals vaccinated with formalin-inactivated viral antigens. Here we explore this paradigm with pneumonia virus of mice (PVM), a pathogen that faithfully reproduces features of severe hRSV infection in a rodent host. We demonstrate that PVM infection in mice vaccinated with formalin-inactivated antigens from PVM-infected cells (PVM Ags) yields Th2-skewed hypersensitivity, analogous to that observed in response to hRSV. Specifically, we detect elevated levels of IL-4, IL-5, IL-13, and eosinophils in bronchoalveolar lavage (BAL) fluid of PVM-infected mice that were vaccinated with PVM Ags, but not among mice vaccinated with formalin-inactivated antigens from uninfected cells (Ctrl Ags). Interestingly, infection in PVM Ag-vaccinated mice was associated with a ~10-fold reduction in lung virus titer and protection against weight loss when compared to infected mice vaccinated with Ctrl Ags, despite the absence of serum neutralizing antibodies. Given recent findings documenting a role for eosinophils in promoting clearance of hRSV in vivo, we explored the role of eosinophils in altering the pathogenesis of disease with eosinophil-deficient mice. We found that eosinophil deficiency had no impact on virus titer in PVM Ags-vaccinated mice, nor on weight loss or levels of CCL11 (eotaxin-1), interferon-γ, interleukin (IL)-5, or IL-13 in BAL fluid. However, levels of both IL-4 and CCL3 (macrophage inflammatory protein-1α) in BAL fluid were markedly diminished in PVM Ag-vaccinated, PVM-infected eosinophil-deficient mice when compared to wild type controls (246 words). PMID:19542471

  9. RAP-011, an activin receptor ligand trap, increases hemoglobin concentration in hepcidin transgenic mice.

    PubMed

    Langdon, Jacqueline M; Barkataki, Sangjucta; Berger, Alan E; Cheadle, Chris; Xue, Qian-Li; Sung, Victoria; Roy, Cindy N

    2015-01-01

    Over expression of hepcidin antimicrobial peptide is a common feature of iron-restricted anemia in humans. We investigated the erythroid response to either erythropoietin or RAP-011, a "murinized" ortholog of sotatercept, in C57BL/6 mice and in hepcidin antimicrobial peptide 1 over expressing mice. Sotatercept, a soluble, activin receptor type IIA ligand trap, is currently being evaluated for the treatment of anemias associated with chronic renal disease, myelodysplastic syndrome, β-thalassemia, and Diamond Blackfan anemia and acts by inhibiting signaling downstream of activin and other Transforming Growth Factor-β superfamily members. We found that erythropoietin and RAP-011 increased hemoglobin concentration in C57BL/6 mice and in hepcidin antimicrobial peptide 1 over expressing mice. While erythropoietin treatment depleted splenic iron stores in C57BL/6 mice, RAP-011 treatment did not deplete splenic iron stores in mice of either genotype. Bone marrow erythroid progenitors from erythropoietin-treated mice exhibited iron-restricted erythropoiesis, as indicated by increased median fluorescence intensity of transferrin receptor immunostaining by flow cytometry. In contrast, RAP-011-treated mice did not exhibit the same degree of iron-restricted erythropoiesis. In conclusion, we have demonstrated that RAP-011 can improve hemoglobin concentration in hepcidin antimicrobial peptide 1 transgenic mice. Our data support the hypothesis that RAP-011 has unique biologic effects which prevent or circumvent depletion of mouse splenic iron stores. RAP-011 may, therefore, be an appropriate therapeutic for trials in human anemias characterized by increased expression of hepcidin antimicrobial peptide and iron-restricted erythropoiesis.

  10. Exploration Technology Development & Demonstration

    NASA Video Gallery

    Chris Moore delivers a presentation from the Exploration Technology Development & Demonstration (ETDD) study team on May 25, 2010, at the NASA Exploration Enterprise Workshop held in Galveston, TX....

  11. LIMB demonstration project extension

    SciTech Connect

    Not Available

    1990-09-21

    The purpose of the DOE limestone injection multistage burner (LIMB) Demonstration Project Extension is to extend the data base on LIMB technology and to expand DOE's list of Clean Coal Technologies by demonstrating the Coolside process as part of the project. The main objectives of this project are: to demonstrate the general applicability of LIMB technology by testing 3 coals and 4 sorbents (total of 12 coal/sorbent combinations) at the Ohio Edison Edgewater plant; and to demonstrate that Coolside is a viable technology for improving precipitator performance and reducing sulfur dioxide emissions while acceptable operability is maintained. Progress is reported. 3 figs.

  12. Demonstrating Bacterial Flagella.

    ERIC Educational Resources Information Center

    Porter, John R.; And Others

    1992-01-01

    Describes an effective laboratory method for demonstrating bacterial flagella that utilizes the Proteus mirabilis organism and a special harvesting technique. Includes safety considerations for the laboratory exercise. (MDH)

  13. Extra-prostatic Transgene-associated Neoplastic Lesions in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice

    PubMed Central

    Berman-Booty, Lisa D.; Thomas-Ahner, Jennifer M.; Bolon, Brad; Oglesbee, Michael J.; Clinton, Steven K.; Kulp, Samuel K.; Chen, Ching-Shih; La Perle, Krista

    2014-01-01

    Male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice are frequently used in prostate cancer research because their prostates consistently develop a series of pre-neoplastic and neoplastic lesions. Disease progression in TRAMP mouse prostates culminates in metastatic, poorly differentiated carcinomas with neuroendocrine features. The androgen dependence of the rat probasin promoter largely limits transgene expression to the prostatic epithelium. However, extra-prostatic transgene-positive lesions have been described in TRAMP mice, including renal tubulo-acinar carcinomas, neuroendocrine carcinomas of the urethra, and phyllodes-like tumors of the seminal vesicle. Here we describe the histologic and immunohistochemical features of two novel extra-prostatic lesions in TRAMP mice: primary anaplastic tumors of uncertain cell origin in the midbrain, and poorly differentiated adenocarcinomas of the submandibular salivary gland. These newly characterized tumors apparently result from transgene expression in extra-prostatic locations rather than representing metastatic prostate neoplasms because lesions were identified in both male and female mice as well as in male TRAMP mice without histologically apparent prostate tumors. In this paper we also calculate the incidences of the urethral carcinomas and renal tubulo-acinar carcinomas, further elucidate the biological behavior of the urethral carcinomas, and demonstrate the critical importance of complete necropsies even when evaluating presumably well characterized phenotypes in genetically engineered mice. PMID:24742627

  14. Extra-prostatic transgene-associated neoplastic lesions in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice.

    PubMed

    Berman-Booty, Lisa D; Thomas-Ahner, Jennifer M; Bolon, Brad; Oglesbee, Michael J; Clinton, Steven K; Kulp, Samuel K; Chen, Ching-Shih; La Perle, Krista M D

    2015-02-01

    Male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice are frequently used in prostate cancer research because their prostates consistently develop a series of preneoplastic and neoplastic lesions. Disease progression in TRAMP mouse prostates culminates in metastatic, poorly differentiated carcinomas with neuroendocrine features. The androgen dependence of the rat probasin promoter largely limits transgene expression to the prostatic epithelium. However, extra-prostatic transgene-positive lesions have been described in TRAMP mice, including renal tubuloacinar carcinomas, neuroendocrine carcinomas of the urethra, and phyllodes-like tumors of the seminal vesicle. Here, we describe the histologic and immunohistochemical features of 2 novel extra-prostatic lesions in TRAMP mice: primary anaplastic tumors of uncertain cell origin in the midbrain and poorly differentiated adenocarcinomas of the submandibular salivary gland. These newly characterized tumors apparently result from transgene expression in extra-prostatic locations rather than representing metastatic prostate neoplasms because lesions were identified in both male and female mice and in male TRAMP mice without histologically apparent prostate tumors. In this article, we also calculate the incidences of the urethral carcinomas and renal tubuloacinar carcinomas, further elucidate the biological behavior of the urethral carcinomas, and demonstrate the critical importance of complete necropsies even when evaluating presumably well characterized phenotypes in genetically engineered mice.

  15. Tested Demonstrations: Spectroscopy Illustrated.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1983-01-01

    Background information and procedures are provided for an experiment to prepare three metal derivatives of dimethyl sulfoxide (DMSO) and to determine some structural features of these derivatives based on their infrared spectra. Results and discussion of reactions involved are also provided. (JN)

  16. Microgravity Plant Growth Demonstration

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Two visitors watch a TV monitor showing plant growth inside a growth chamber designed for operation aboard the Space Shuttle as part of NASA's Space Product Development program. The exhibit, featuring work by the Wisconsin Center for Space Automation and Robotics, was at AirVenture 2000 sponsored by the Experimental Aircraft Association in Oshkosh, WI.

  17. Demonstrating Phase Changes.

    ERIC Educational Resources Information Center

    Rohr, Walter

    1995-01-01

    Presents two experiments that demonstrate phase changes. The first experiment explores phase changes of carbon dioxide using powdered dry ice sealed in a piece of clear plastic tubing. The second experiment demonstrates an equilibrium process in which a crystal grows in equilibrium with its saturated solution. (PVD)

  18. Levitation Kits Demonstrate Superconductivity.

    ERIC Educational Resources Information Center

    Worthy, Ward

    1987-01-01

    Describes the "Project 1-2-3" levitation kit used to demonstrate superconductivity. Summarizes the materials included in the kit. Discusses the effect demonstrated and gives details on how to obtain kits. Gives an overview of the documentation that is included. (CW)

  19. USFWS demonstration fees

    USGS Publications Warehouse

    Taylor, Jonathan; Vaske, Jerry; Donnelly, Maureen; Shelby, Lori

    2002-01-01

    This study examined National Wildlife Refuge (NWR) visitors' reactions to changes in fees implemented as part of the fee demonstration program. Visitors' evaluations of the fees paid were examined in addition to their beliefs about fees and the fee demonstration program, and the impact of fees paid on their intention to return. All results were analyzed relative to socio-demographic characteristics.

  20. A Stellar Demonstrator

    ERIC Educational Resources Information Center

    Ros, Rosa M.

    2009-01-01

    The main purpose of the stellar demonstrator is to help explain the movement of stars. In particular, students have difficulties understanding why, if they are living in the Northern Hemisphere, they may observe starts in the Southern Hemisphere, or why circumpolar stars are not the same in different parts of Europe. Using the demonstrator, these…

  1. Toy Demonstrator's "VISIT" Handbook.

    ERIC Educational Resources Information Center

    Levenstein, Phyllis

    The role of the toy demonstrator in a home-based, mother-involved intervention effort (Verbal Interaction Project) is presented in this handbook for staff members. It is believed that the prerequisites for functioning in the toy demonstrator's role are a sense of responsibility, patience with the children and their mothers, and willingness to be…

  2. Demonstrating Reduced Gravity

    NASA Technical Reports Server (NTRS)

    Pearlman, Howard; Stocker, Dennis; Gotti, Daniel; Urban, David; Ross, Howard; Sours, Thomas

    1996-01-01

    A miniature drop tower, Reduced-Gravity Demonstrator is developed to illustrate the effects of gravity on a variety of phenomena including the way fluids flow, flames burn, and mechanical systems (such as pendulum) behave. A schematic and description of the demonstrator and payloads are given, followed by suggestions for how one can build his (her) own.

  3. Better Ira Remsen Demonstration

    ERIC Educational Resources Information Center

    Dalby, David K.; Maynard, James H.; Moore, John W.

    2011-01-01

    Many versions of the classic Ira Remsen experience involving copper and concentrated nitric acid have been used as lecture demonstrations. Remsen's original reminiscence from 150 years ago is included in the Supporting Information, and his biography can be found on the Internet. This article presents a new version that makes the demonstration more…

  4. Kinetics and Catalysis Demonstrations.

    ERIC Educational Resources Information Center

    Falconer, John L.; Britten, Jerald A.

    1984-01-01

    Eleven videotaped kinetics and catalysis demonstrations are described. Demonstrations include the clock reaction, oscillating reaction, hydrogen oxidation in air, hydrogen-oxygen explosion, acid-base properties of solids, high- and low-temperature zeolite reactivity, copper catalysis of ammonia oxidation and sodium peroxide decomposition, ammonia…

  5. A Greener Chemiluminescence Demonstration

    ERIC Educational Resources Information Center

    Jilani, Osman; Donahue, Trisha M.; Mitchell, Miguel O.

    2011-01-01

    Because they are dramatic and intriguing, chemiluminescence demonstrations have been used for decades to stimulate interest in chemistry. One of the most intense chemiluminescent reactions is the oxidation of diaryl oxalate diesters with hydrogen peroxide in the presence of a fluorescer. In typical lecture demonstrations, the commercially…

  6. Demonstration Experiments in Physics

    ERIC Educational Resources Information Center

    Sutton, Richard M.

    2003-01-01

    This book represents a "cookbook" for teachers of physics, a book of recipes for the preparation of demonstration experiments to illustrate the principles that make the subject of physics so fascinating. Illustrations and explanations of each demonstration are done in an easy-to-understand format. Each can be adapted to be used as a demonstration…

  7. The Microgravity Demonstrator.

    ERIC Educational Resources Information Center

    Rogers, Melissa J. B.; Wargo, Michael J.

    The Microgravity Demonstrator is a tool used to create microgravity conditions in the classroom. A series of demonstrations is used to provide a dramatically visual, physical connection between free-fall and microgravity conditions in order to understand why various types of experiments are performed under microgravity conditions. The manual is…

  8. Demonstrating Newton's Second Law.

    ERIC Educational Resources Information Center

    Fricker, H. S.

    1994-01-01

    Describes an apparatus for demonstrating the second law of motion. Provides sample data and discusses the merits of this method over traditional methods of supplying a constant force. The method produces empirical best-fit lines which convincingly demonstrate that for a fixed mass, acceleration is proportional to force. (DDR)

  9. Using an OHP to Demonstrate Wave Motion.

    ERIC Educational Resources Information Center

    Jacobs, F.

    1985-01-01

    Describes how, using an overhead projector (OHP) and a transparent roll of acetate film, it is possible to demonstrate: (1) travelling waves; (2) standing waves; and (3) phase and group velocity applied to waves. The set-ups provide a way to demonstrate features which are normally difficult to visualize and understand. (JN)

  10. Experimental Demonstrations in Teaching Chemical Reactions.

    ERIC Educational Resources Information Center

    Hugerat, Muhamad; Basheer, Sobhi

    2001-01-01

    Presents demonstrations of chemical reactions by employing different features of various compounds that can be altered after a chemical change occurs. Experimental activities include para- and dia-magnetism in chemical reactions, aluminum reaction with base, reaction of acid with carbonates, use of electrochemical cells for demonstrating chemical…

  11. METCAN demonstration manual, version 1.0

    NASA Technical Reports Server (NTRS)

    Lee, H.-J.; Murthy, P. L. N.

    1992-01-01

    The various features of the Metal Matrix Composite Analyzer (METCAN) computer program to simulate the high temperature nonlinear behavior of continuous fiber reinforced metal matrix composites are demonstrated. Different problems are used to demonstrate various capabilities of METCAN for both static and cyclic analyses. A complete description of the METCAN output file is also included to help interpret results.

  12. MICE Staging and Status

    NASA Astrophysics Data System (ADS)

    Hanlet, Pierrick

    2010-03-01

    Ionization cooling will be a key technique for a high-intensity Neutrino Factory or Muon Collider. The Muon Ionization Cooling Experiment (MICE) is a high-precision, staged accelerator experiment being performed at Rutherford Appleton Laboratory in the UK. Its goal is the first demonstration, with 0.1% resolution, of the feasibility of reducing the transverse emittance of a beam of muons by ionization cooling in low-Z absorbers. MICE is being staged in the following steps: I. Creating and characterizing a beam of muons; II. Measuring their emittance; III. Systematic comparison of successive measurements; IV. Inserting absorber; V. Reaccelerating longitudinally; and VI. Complete "10%-cooling" test. Step I is currently in progress with Step II to commence next year; completion of Step VI is anticipated in ˜2012.

  13. Defective transcription-coupled repair in Cockayne syndrome B mice is associated with skin cancer predisposition.

    PubMed

    van der Horst, G T; van Steeg, H; Berg, R J; van Gool, A J; de Wit, J; Weeda, G; Morreau, H; Beems, R B; van Kreijl, C F; de Gruijl, F R; Bootsma, D; Hoeijmakers, J H

    1997-05-01

    A mouse model for the nucleotide excision repair disorder Cockayne syndrome (CS) was generated by mimicking a truncation in the CSB(ERCC6) gene of a CS-B patient. CSB-deficient mice exhibit all of the CS repair characteristics: ultraviolet (UV) sensitivity, inactivation of transcription-coupled repair, unaffected global genome repair, and inability to resume RNA synthesis after UV exposure. Other CS features thought to involve the functioning of basal transcription/repair factor TFIIH, such as growth failure and neurologic dysfunction, are present in mild form. In contrast to the human syndrome, CSB-deficient mice show increased susceptibility to skin cancer. Our results demonstrate that transcription-coupled repair of UV-induced cyclobutane pyrimidine dimers contributes to the prevention of carcinogenesis in mice. Further, they suggest that the lack of cancer predisposition in CS patients is attributable to a global genome repair process that in humans is more effective than in rodents. PMID:9150142

  14. [Peritoneal biofilms: microscopic features].

    PubMed

    Maloman, E; Lepadatu, C; Ciornâi, A; Sainsus, Natalia; Balica, I; Gladun, N

    2007-01-01

    Antibiotherapy remains one of the basic clinical tools, which can influence the evolution of severe peritonitis. Peritoneal biofilm formation may minimize the antibiotic effects due to dramatic growth of Minimum Inhibitory Concentrations (MIC) and Minimum Bactericidal Concentrations (MBC) for matrix-enclosed bacteria. In this paper we demonstrate the presence and evolution of bacterial biofilms on the peritoneal surface during the course of severe secondary peritonitis using an experimental model and clinical material. Cecal Ligation Puncture was performed in 20 mice Swiss Webster. Peritoneal samples were studied at optic and electronic microscope at 10, 24, 48 and 72 hours postoperative. Clinical samples were taken from 10 patients with diffuse peritonitis. At 24 hours after the onset of the peritonitis bacterial colonies were detected on the peritoneal surface. The formation of mature multilayer polymicrobial biofilms with deep penetration in abdominal wall by 48-72 hours was documented. The bacterial biofilms appear in first 24 hours in the course of experimental generalized peritonitis. Our experimental and clinical data demonstrate formation of the mature polymicrobial biofilm in 48-72 hours after the onset of peritonitis. The possibility of resistant biofilm formation in secondary diffuse peritonitis should be taken into consideration in elaboration of treatment schemes.

  15. Demonstrating Natural Selection

    ERIC Educational Resources Information Center

    Hinds, David S.; Amundson, John C.

    1975-01-01

    Describes laboratory exercises with chickens selecting their food from dyed and natural corn kernels as a method of demonstrating natural selection. The procedure is based on the fact that organisms that blend into their surroundings escape predation. (BR)

  16. Flagship Technology Demonstrations (FTD)

    NASA Video Gallery

    Mike Conley delivers a presentation from the Flagship Technology Demonstrations (FTD) study team on May 25, 2010, at the NASA Exploration Enterprise Workshop held in Galveston, TX. The purpose of t...

  17. Technology Demonstration Missions

    NASA Video Gallery

    NASA's Technology Demonstration Missions (TDM) Program seeks to infuse new technology into space applications, bridging the gap between mature “lab-proven” technology and "flight-ready" status....

  18. Floating Magnet Demonstration.

    ERIC Educational Resources Information Center

    Wake, Masayoshi

    1990-01-01

    A room-temperature demonstration of a floating magnet using a high-temperature superconductor is described. The setup and operation of the apparatus are described. The technical details of the effect are discussed. (CW)

  19. Spacecraft servicing demonstration plan

    NASA Technical Reports Server (NTRS)

    Bergonz, F. H.; Bulboaca, M. A.; Derocher, W. L., Jr.

    1984-01-01

    A preliminary spacecraft servicing demonstration plan is prepared which leads to a fully verified operational on-orbit servicing system based on the module exchange, refueling, and resupply technologies. The resulting system can be applied at the space station, in low Earth orbit with an orbital maneuvering vehicle (OMV), or be carried with an OMV to geosynchronous orbit by an orbital transfer vehicle. The three phase plan includes ground demonstrations, cargo bay demonstrations, and free flight verifications. The plan emphasizes the exchange of multimission modular spacecraft (MMS) modules which involves space repairable satellites. Three servicer mechanism configurations are the engineering test unit, a protoflight quality unit, and two fully operational units that have been qualified and documented for use in free flight verification activity. The plan balances costs and risks by overlapping study phases, utilizing existing equipment for ground demonstrations, maximizing use of existing MMS equipment, and rental of a spacecraft bus.

  20. EVA Retriever Demonstration

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The EVA retriever is demonstrated in the Manipulator Development Facility (MDF). The retriever moves on the air bearing table 'searching' for its target, in this case tools 'dropped' by astronauts on orbit.

  1. Commissioning the Majorana Demonstrator

    NASA Astrophysics Data System (ADS)

    Xu, Wenqin; Majorana Collaboration

    2016-03-01

    The Majorana Demonstrator deploys high purity germanium (HPGe) detector modules to search for neutrinoless double beta (0 νββ) decay in 76Ge. The experiment is aimed at demonstrating the technical feasibility and low backgrounds for a next generation Ge-based BBz experiment. The program of testing and commissioning the Demonstrator modules is a critical step to debug and improve the experimental apparatus, to establish and refine operational procedures, and to develop data analysis tools. In this talk, we will discuss our experience commissioning the Demonstrator modules and show how this program leads to successful data-taking. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Nuclear Physics, the Particle Astrophysics and Nuclear Physics Programs of the National Science Foundation, and the Sanford Underground Research Facility.

  2. Methanol Cannon Demonstrations Revisited.

    ERIC Educational Resources Information Center

    Dolson, David A.; And Others

    1995-01-01

    Describes two variations on the traditional methanol cannon demonstration. The first variation is a chain reaction using real metal chains. The second example involves using easily available components to produce sequential explosions that can be musical in nature. (AIM)

  3. Five amazing physics demonstrations

    NASA Astrophysics Data System (ADS)

    Downie, Neil

    2015-04-01

    There's nothing better than a good physics demonstration to illustrate the subject's fundamental principles. Neil Downie, who has run Saturday science clubs for children for more than two decades, presents his five best demos of all time.

  4. Demonstration of Surface Tension.

    ERIC Educational Resources Information Center

    Rosenthal, Andrew J.

    2001-01-01

    Surface tension is a fundamental obstacle in the spontaneous formation of bubbles, droplets, and crystal nuclei in liquids. Describes a simple overhead projector demonstration that illustrates the power of surface tension that can prevent so many industrial processes. (ASK)

  5. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Hambly, Gordon F.; Goldsmith, Robert H.

    1988-01-01

    Presented is a method of demonstrating the optical activity of glucose using an overhead projector and easily obtainable materials. Explores the difference between reflected and transmitted light (Tyndall Effect) using sodium thiosulfate, hydrochloric acid, and an overhead projector. (ML)

  6. Classroom Demonstration of Sunspots.

    ERIC Educational Resources Information Center

    Callaway, Thomas O.; And Others

    1982-01-01

    An overhead projector, projection screen, and clear tungsten Filament light bulb operated through a dimmer or variac switch are used to demonstrate the fact that black appearance of sunspots is due only to contrast and that sunspots are bright. (SK)

  7. Remote Agent Demonstration

    NASA Technical Reports Server (NTRS)

    Dorais, Gregory A.; Kurien, James; Rajan, Kanna

    1999-01-01

    We describe the computer demonstration of the Remote Agent Experiment (RAX). The Remote Agent is a high-level, model-based, autonomous control agent being validated on the NASA Deep Space 1 spacecraft.

  8. Feature++: Automatic Feature Construction for Clinical Data Analysis.

    PubMed

    Sun, Wen; Hao, Bibo; Yu, Yiqin; Li, Jing; Hu, Gang; Xie, Guotong

    2016-01-01

    With the rapid growth of clinical data and knowledge, feature construction for clinical analysis becomes increasingly important and challenging. Given a clinical dataset with up to hundreds or thousands of columns, the traditional manual feature construction process is usually too labour intensive to generate a full spectrum of features with potential values. As a result, advanced large-scale data analysis technologies, such as feature selection for predictive modelling, cannot be fully utilized for clinical data analysis. In this paper, we propose an automatic feature construction framework for clinical data analysis, namely, Feature++. It leverages available public knowledge to understand the semantics of the clinical data, and is able to integrate external data sources to automatically construct new features based on predefined rules and clinical knowledge. We demonstrate the effectiveness of Feature++ in a typical predictive modelling use case with a public clinical dataset, and the results suggest that the proposed approach is able to fulfil typical feature construction tasks with minimal dataset specific configurations, so that more accurate models can be obtained from various clinical datasets in a more efficient way. PMID:27577443

  9. Education Payload Operation - Demonstrations

    NASA Technical Reports Server (NTRS)

    Keil, Matthew

    2009-01-01

    Education Payload Operation - Demonstrations (EPO-Demos) are recorded video education demonstrations performed on the International Space Station (ISS) by crewmembers using hardware already onboard the ISS. EPO-Demos are videotaped, edited, and used to enhance existing NASA education resources and programs for educators and students in grades K-12. EPO-Demos are designed to support the NASA mission to inspire the next generation of explorers.

  10. Central diabetes insipidus associated with impaired renal aquaporin-1 expression in mice lacking liver X receptor β.

    PubMed

    Gabbi, Chiara; Kong, Xiaomu; Suzuki, Hitoshi; Kim, Hyun-Jin; Gao, Min; Jia, Xiao; Ohnishi, Hideo; Ueta, Yoichi; Warner, Margaret; Guan, Youfei; Gustafsson, Jan-Åke

    2012-02-21

    The present study demonstrates a key role for the oxysterol receptor liver X receptor β (LXRβ) in the etiology of diabetes insipidus (DI). Given free access to water, LXRβ(-/-) but not LXRα(-/-) mice exhibited polyuria (abnormal daily excretion of highly diluted urine) and polydipsia (increased water intake), both features of diabetes insipidus. LXRβ(-/-) mice responded to 24-h dehydration with a decreased urine volume and increased urine osmolality. To determine whether the DI was of central or nephrogenic origin, we examined the responsiveness of the kidney to arginine vasopressin (AVP). An i.p. injection of AVP to LXRβ(-/-) mice revealed a partial kidney response: There was no effect on urine volume, but there was a significant increase of urine osmolality, suggesting that DI may be caused by a defect in central production of AVP. In the brain of WT mice LXRβ was expressed in the nuclei of magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus. In LXRβ(-/-) mice the expression of AVP was markedly decreased in the magnocellular neurons as well as in urine collected over a 24-h period. The persistent high urine volume after AVP administration was traced to a reduction in aquaporin-1 expression in the kidney of LXRβ(-/-) mice. The LXR agonist (GW3965) in WT mice elicited an increase in urine osmolality, suggesting that LXRβ is a key receptor in controlling water balance with targets in both the brain and kidney, and it could be a therapeutic target in disorders of water balance.

  11. Edible Astronomy Demonstrations

    NASA Astrophysics Data System (ADS)

    Lubowich, Donald A.

    2007-12-01

    Astronomy demonstrations with edible ingredients are an effective way to increase student interest and knowledge of astronomical concepts. This approach has been successful with all age groups from elementary school through college students - and the students remember these demonstrations after they are presented. In this poster I describe edible demonstrations I have created to simulate the expansion of the universe (using big-bang chocolate chip cookies); differentiation during the formation of the Earth and planets (using chocolate or chocolate milk with marshmallows, cereal, candy pieces or nuts); and radioactivity/radioactive dating (using popcorn). Other possible demonstrations include: plate tectonics (crackers with peanut butter and jelly); convection (miso soup or hot chocolate); mud flows on Mars (melted chocolate poured over angel food cake); formation of the Galactic disk (pizza); formation of spiral arms (coffee with cream); the curvature of Space (Pringles); constellations patterns with chocolate chips and chocolate chip cookies; planet shaped cookies; star shaped cookies with different colored frostings; coffee or chocolate milk measurement of solar radiation; Oreo cookie lunar phases. Sometimes the students eat the results of the astronomical demonstrations. These demonstrations are an effective teaching tool and can be adapted for cultural, culinary, and ethnic differences among the students.

  12. Mice Lacking the p43 Mitochondrial T3 Receptor Become Glucose Intolerant and Insulin Resistant during Aging

    PubMed Central

    Bertrand, Christelle; Blanchet, Emilie; Pessemesse, Laurence; Annicotte, Jean Sébastien; Feillet-Coudray, Christine; Chabi, Béatrice; Levin, Jonathan; Fajas, Lluis; Cabello, Gérard; Wrutniak-Cabello, Chantal; Casas, François

    2013-01-01

    Thyroid hormones (TH) play an important regulatory role in energy expenditure regulation and are key regulators of mitochondrial activity. We have previously identified a mitochondrial triiodothyronine (T3) receptor (p43) which acts as a mitochondrial transcription factor of the organelle genome, which leads in vitro and in vivo, to a stimulation of mitochondrial biogenesis. Recently, we generated mice carrying a specific p43 invalidation. At 2 months of age, we reported that p43 depletion in mice induced a major defect in insulin secretion both in vivo and in isolated pancreatic islets, and a loss of glucose-stimulated insulin secretion. The present study was designed to determine whether p43 invalidation influences life expectancy and modulates blood glucose and insulin levels as well as glucose tolerance or insulin sensitivity during aging. We report that from 4 months old onwards, mice lacking p43 are leaner than wild-type mice. p43−/− mice also have a moderate reduction of life expectancy compared to wild type. We found no difference in blood glucose levels, excepted at 24 months old where p43−/− mice showed a strong hyperglycemia in fasting conditions compared to controls animals. However, the loss of glucose-stimulated insulin secretion was maintained whatever the age of mice lacking p43. If up to 12 months old, glucose tolerance remained unchanged, beyond this age p43−/− mice became increasingly glucose intolerant. In addition, if up to 12 months old p43 deficient animals were more sensitive to insulin, after this age we observed a loss of this capacity, culminating in 24 months old mice with a decreased sensitivity to the hormone. In conclusion, we demonstrated that during aging the depletion of the mitochondrial T3 receptor p43 in mice progressively induced an increased glycemia in the fasted state, glucose intolerance and an insulin-resistance several features of type-2 diabetes. PMID:24098680

  13. Demonstrations in Introductory Geophysics

    NASA Astrophysics Data System (ADS)

    Schramm, K. A.; Stein, S.; van der Lee, S.; Swafford, L.; Klosko, E.; Delaughter, J.; Wysession, M.

    2005-12-01

    Geophysical concepts are challenging to teach at introductory levels, because students need to understand both the underlying physics and its geological application. To address this, our introductory courses include class demonstrations and experiments to demonstrate underlying physical principles and their geological applications. Demonstrations and experiments have several advantages over computer simulations. First, computer simulations "work" even if the basic principle is wrong. In contrast, simple demonstrations show that a principle is physically correct, rather than a product of computer graphics. Second, many students are unfamiliar with once-standard experiments demonstrating ideas of classical physics used in geophysics. Demonstrations are chosen that we consider stimulating, relevant, inexpensive, and easy to conduct in a non-lab classroom. These come in several groups. Many deal with aspects of seismic waves, using springs, light beams, and other methods such as talking from outside the room to illustrate the frequency dependence of diffraction (hearing but not seeing around a corner). Others deal with heat and mass transfer, such as illustrating fractional crystallization with apple juice and the surface/volume effect in planetary evolution with ice. Plate motions are illustrated with paper cutouts showing effects like motion on transform faults and how the Euler vector geometry changes a plate boundary from spreading, to strike-slip, to convergence along the Pacific-North America boundary from the Gulf of California to Alaska. Radioactive decay is simulated by having the class rise and sit down as a result of coin flips (one tail versus two gives different decay rates and hence half lives). This sessions' goal of exchanging information about demonstrations is an excellent idea: some of ours are described on http://www.earth.nwu.edu/people/seth/202.

  14. Progress of the MICE experiment

    NASA Astrophysics Data System (ADS)

    Bonesini, M.

    The international Muon Ionization Cooling Experiment (MICE) will perform a systematic investigation of ionization cooling of a muon beam. The demonstration is based on a simplified version of a neutrino factory cooling channel. As the emittance measurement will be done on a particle-by-particle basis, sophisticated beam instrumentation has been developed to measure particle coordinates and timing vs RF. The muon beamline has been characterized and a preliminary measure of the beam emittance, using a particle-by-particle method with only the TOF detector system, has been performed (MICE STEP I). Data taking for the study of the properties that determine the cooling performance (MICE Step IV) has just started in 2015, while the demonstration of ionization cooling with re-acceleration is foreseen for 2017.

  15. Solar Energy Demonstrations

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Solar energy furnishes all of the heating and hot water needs, plus 80 percent of the air conditioning, for the two-story Reedy Creek building. A unique feature of this installation is that the 16 semi-cylindrical solar collectors (center photo on opposite page with closeup of a single collector below it) are not mounted atop the roof as is customary, they actually are the roof. This arrangement eliminates the usual trusses, corrugated decking and insulating concrete in roof construction; that, in turn, reduces overall building costs and makes the solar installation more attractive economically. The Reedy Creek collectors were designed and manufactured by AAI Corporation of Baltimore, Maryland.

  16. TRUEX hot demonstration

    SciTech Connect

    Chamberlain, D.B.; Leonard, R.A.; Hoh, J.C.; Gay, E.C.; Kalina, D.G.; Vandegrift, G.F.

    1990-04-01

    In FY 1987, a program was initiated to demonstrate technology for recovering transuranic (TRU) elements from defense wastes. This hot demonstration was to be carried out with solution from the dissolution of irradiated fuels. This recovery would be accomplished with both PUREX and TRUEX solvent extraction processes. Work planned for this program included preparation of a shielded-cell facility for the receipt and storage of spent fuel from commercial power reactors, dissolution of this fuel, operation of a PUREX process to produce specific feeds for the TRUEX process, operation of a TRUEX process to remove residual actinide elements from PUREX process raffinates, and processing and disposal of waste and product streams. This report documents the work completed in planning and starting up this program. It is meant to serve as a guide for anyone planning similar demonstrations of TRUEX or other solvent extraction processing in a shielded-cell facility.

  17. Demonstrating marketing accountability.

    PubMed

    Gombeski, William R; Britt, Jason; Taylor, Jan; Riggs, Karen; Wray, Tanya; Adkins, Wanda; Springate, Suzanne

    2008-01-01

    Pressure on health care marketers to demonstrate effectiveness of their strategies and show their contribution to organizational goals is growing. A seven-tiered model based on the concepts of structure (having the right people, systems), process (doing the right things in the right way), and outcomes (results) is discussed. Examples of measures for each tier are provided and the benefits of using the model as a tool for measuring, organizing, tracking, and communicating appropriate information are provided. The model also provides a framework for helping management understand marketing's value and can serve as a vehicle for demonstrating marketing accountability.

  18. Gigashot Optical Laser Demonstrator

    SciTech Connect

    Deri, R. J.

    2015-10-13

    The Gigashot Optical Laser Demonstrator (GOLD) project has demonstrated a novel optical amplifier for high energy pulsed lasers operating at high repetition rates. The amplifier stores enough pump energy to support >10 J of laser output, and employs conduction cooling for thermal management to avoid the need for expensive and bulky high-pressure helium subsystems. A prototype amplifier was fabricated, pumped with diode light at 885 nm, and characterized. Experimental results show that the amplifier provides sufficient small-signal gain and sufficiently low wavefront and birefringence impairments to prove useful in laser systems, at repetition rates up to 60 Hz.

  19. Modular hydropower demonstration

    SciTech Connect

    Not Available

    1988-09-01

    The modular approach has been developed for the construction of small hydro projects in order to reduce the costs and to shorten procurement and construction schedules that occur when designs and equipment selection more applicable to large projects are used. The modular approach aims to maximize the use of ''off-the-shelf'' and readily available components. A key feature is the replacement of the conventional purpose-designed hydroelectric turbine by a pump used in reverse as a turbine with fixed blades and vanes. Other features are the use of siphon penstocks, induction generators, prefabricated structures, and automated control equipment. The New York State Energy Research and Development Authority contracted with Acres International Corporation to study two small hydro projects designed and built using the modular approach, and compare each one with an equivalent conventional design. Equipment procurement and installation costs, general construction costs, and energy production were estimated. Economic analyses were prepared. Preliminary data on operation and maintenance was recorded. The methodology and results of the study are contained in this report. 18 figs., 20 tabs.

  20. Phenolphthalein—Pink Tornado Demonstration

    NASA Astrophysics Data System (ADS)

    Prall, Bruce R.

    2008-04-01

    The phenolphthalein-pink tornado demonstration utilizes the vortex generated by a spinning magnetic stirring bar in a 1 L graduated cylinder containing 0.01 M HCl to demonstrate Le Châtelier's principle as it applies to the phenolphthalein equilibrium in water H 2 In + 2H 2 O 2H 2 O + + In 2 - where H 2 In is phenophthalein. The addition of 3-4 drops of phenolphthalein indicator solution followed immediately by 3-4 drops of 50% (w/w) NaOH to the vortex of the HCl solution results in a shift to the right in the equilibrium owing to the reaction of OH - + H 3 O + to form water. This shift is accompanied by the vortex becoming visible by the appearance of a pinkish-red color caused by an increase in In 2- concentration within the localized region of the vortex. The demonstration also provides one an excellent opportunity to discuss the topics of limiting reagent and reagent in excess. Some insight regarding the extent to which uniform mixing is achieved when using a magnetic stirrer is also provided. Included is a note from the Feature Editor, Ed Vitz.

  1. Organic Lecture Demonstrations.

    ERIC Educational Resources Information Center

    Silversmith, Ernest F.

    1988-01-01

    Provides a listing of 35 demonstrations designed to generate interest in organic chemistry and help put points across. Topics include opening lecture; molecular structure and properties; halogenation; nucleophilic substitution, alkenes and dienes, stereochemistry, spectroscopy, alcohols and phenols, aldehydes and ketones; carboxylic acids, amines,…

  2. Calculus Demonstrations Using MATLAB

    ERIC Educational Resources Information Center

    Dunn, Peter K.; Harman, Chris

    2002-01-01

    The note discusses ways in which technology can be used in the calculus learning process. In particular, five MATLAB programs are detailed for use by instructors or students that demonstrate important concepts in introductory calculus: Newton's method, differentiation and integration. Two of the programs are animated. The programs and the…

  3. A Magnetic Circuit Demonstration.

    ERIC Educational Resources Information Center

    Vanderkooy, John; Lowe, June

    1995-01-01

    Presents a demonstration designed to illustrate Faraday's, Ampere's, and Lenz's laws and to reinforce the concepts through the analysis of a two-loop magnetic circuit. Can be made dramatic and challenging for sophisticated students but is suitable for an introductory course in electricity and magnetism. (JRH)

  4. Participatory Lecture Demonstrations.

    ERIC Educational Resources Information Center

    Battino, Rubin

    1979-01-01

    The use of participatory lecture demonstrations in the classroom is described. Examples are given for the following topics: chromatography, chemical kinetics, balancing equations, the gas laws, kinetic molecular theory, Henry's law of gas solubility, electronic energy levels in atoms, and translational, vibrational, and rotational energies of…

  5. Demonstrating carbon capture

    SciTech Connect

    Qader, A.; Hooper, B.; Stevens, G.

    2009-11-15

    Australia is at the forefront of advancing CCS technology. The CO2CRC's H3 (Post-combustion) and Mulgrave (pre-combustion) capture projects are outlined. The capture technologies for these 2 demonstration projects are described. 1 map., 2 photos.

  6. Demonstrating Poisson Statistics.

    ERIC Educational Resources Information Center

    Vetterling, William T.

    1980-01-01

    Describes an apparatus that offers a very lucid demonstration of Poisson statistics as applied to electrical currents, and the manner in which such statistics account for shot noise when applied to macroscopic currents. The experiment described is intended for undergraduate physics students. (HM)

  7. Passive damping technology demonstration

    NASA Astrophysics Data System (ADS)

    Holman, Robert E.; Spencer, Susan M.; Austin, Eric M.; Johnson, Conor D.

    1995-05-01

    A Hughes Space Company study was undertaken to (1) acquire the analytical capability to design effective passive damping treatments and to predict the damped dynamic performance with reasonable accuracy; (2) demonstrate reasonable test and analysis agreement for both baseline and damped baseline hardware; and (3) achieve a 75% reduction in peak transmissibility and 50% reduction in rms random vibration response. Hughes Space Company teamed with CSA Engineering to learn how to apply passive damping technology to their products successfully in a cost-effective manner. Existing hardware was selected for the demonstration because (1) previous designs were lightly damped and had difficulty in vibration test; (2) multiple damping concepts could be investigated; (3) the finite element model, hardware, and test fixture would be available; and (4) damping devices could be easily implemented. Bracket, strut, and sandwich panel damping treatments that met the performance goals were developed by analysis. The baseline, baseline with damped bracket, and baseline with damped strut designs were built and tested. The test results were in reasonable agreement with the analytical predictions and demonstrated that the desired reduction in dynamic response could be achieved. Having successfully demonstrated this approach, it can now be used with confidence for future designs as a means for reducing weight and enhancing reliability.

  8. The "Golden Penny" Demonstration.

    ERIC Educational Resources Information Center

    Szczepankiewicz, Steven H.; And Others

    1995-01-01

    Presents the view that the explanation of the Golden Penny Experiment found in popular chemistry textbooks is insufficient or incorrect in part. Reports a series of electrochemical measurements that lead to a logical explanation for this demonstration and to a simplified design that makes it safer. (DDR)

  9. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Kolb, Doris, Ed.

    1988-01-01

    Provides two demonstrations: (1) electrolyte migration of ions using colored ions which cross a strip of gelatin allowing for noticeable migration; and (2) photochemical reduction of Fe+3 by the citrate ion. Points out both reactions can be done in a Petri dish using common lab materials. (MVL)

  10. Astronomy Demonstrations and Models.

    ERIC Educational Resources Information Center

    Eckroth, Charles A.

    Demonstrations in astronomy classes seem to be more necessary than in physics classes for three reasons. First, many of the events are very large scale and impossibly remote from human senses. Secondly, while physics courses use discussions of one- and two-dimensional motion, three-dimensional motion is the normal situation in astronomy; thus,…

  11. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Kolb, Doris, Ed.

    1989-01-01

    Described are three chemistry demonstrations: (1) a simple qualitative technique for taste pattern recognition in structure-activity relationships; (2) a microscale study of gaseous diffusion using bleach, HCl, ammonia, and phenolphthalein; and (3) the rotation of polarized light by stereoisomers of limonene. (MVL)

  12. Why Demonstrations Matter

    ERIC Educational Resources Information Center

    Black, Richard

    2005-01-01

    The author remembers how exciting it was when the teacher had "stuff" on the front desk: unfamiliar objects and other things out of place in the traditional classroom. Years later, as a new teacher, the author learned the importance of building lessons around concepts and that demonstrations are an integral part of concept development in science.…

  13. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Kolb, Doris, Ed.

    1989-01-01

    Presents two demonstrations using the overhead projector: (1) describes how to build a projecting voltmeter and presents uses for the classroom; and (2) investigates the color of fluorescent solutions by studying the absorption and transmission of light through the solutions. (MVL)

  14. Demonstrating the Gas Laws.

    ERIC Educational Resources Information Center

    Holko, David A.

    1982-01-01

    Presents a complete computer program demonstrating the relationship between volume/pressure for Boyle's Law, volume/temperature for Charles' Law, and volume/moles of gas for Avagadro's Law. The programing reinforces students' application of gas laws and equates a simulated moving piston to theoretical values derived using the ideal gas law.…

  15. A Biofeedback Demonstration.

    ERIC Educational Resources Information Center

    Garrity, Michael K.

    1978-01-01

    Describes a demonstration for measurement of biophysical signals produced by the human body. The signals, after amplification, could provide acoustical feedback through a voltage-controlled oscillator (VCO), or they could be seen either with an oscilloscope or a high speed chart recorder. (GA)

  16. A Fruity Biochemistry Demonstration

    ERIC Educational Resources Information Center

    Shmaefsky, Brian R.

    2005-01-01

    Classroom demonstrations are a great vehicle for getting students to apply information they have heard in a lecture. Educational research is replete with data showing that concept application in an inquiry setting reinforces long-term science content retention. This means that students learn best when they experience applications of concepts and…

  17. The Breaking Broomstick Demonstration.

    ERIC Educational Resources Information Center

    Mamola, Karl C.; Pollock, Joseph T.

    1993-01-01

    Describes and explains the breaking broomstick demonstration first reported in 1532. A needle is fixed at each end of the broomstick, and these needles are made to rest on two glasses, placed on chairs. If the broomstick is struck violently with another stout stick, the former will be broken, but the glasses will remain intact. (PR)

  18. The MICE Run Control System

    NASA Astrophysics Data System (ADS)

    Hanlet, Pierrick; Mice Collaboration

    2014-06-01

    The Muon Ionization Cooling Experiment (MICE) is a demonstration experiment to prove the feasibility of cooling a beam of muons for use in a Neutrino Factory and/or Muon Collider. The MICE cooling channel is a section of a modified Study II cooling channel which will provide a 10% reduction in beam emittance. In order to ensure a reliable measurement, MICE will measure the beam emittance before and after the cooling channel at the level of 1%, or a relative measurement of 0.001. This renders MICE a precision experiment which requires strict controls and monitoring of all experimental parameters in order to control systematic errors. The MICE Controls and Monitoring system is based on EPICS and integrates with the DAQ, Data monitoring systems, and a configuration database. The new MICE Run Control has been developed to ensure proper sequencing of equipment and use of system resources to protect data quality. A description of this system, its implementation, and performance during recent muon beam data collection will be discussed.

  19. Nucla CFB Demonstration Project

    SciTech Connect

    Not Available

    1990-12-01

    This report documents Colorado-Ute Electric Association's Nucla Circulating Atmospheric Fluidized-Bed Combustion (AFBC) demonstration project. It describes the plant equipment and system design for the first US utility-size circulating AFBC boiler and its support systems. Included are equipment and system descriptions, design/background information and appendices with an equipment list and selected information plus process flow and instrumentation drawings. The purpose of this report is to share the information gathered during the Nucla circulating AFBC demonstration project and present it so that the general public can evaluate the technical feasibility and cost effectiveness of replacing pulverized or stoker-fired boiler units with circulating fluidized-bed boiler units. (VC)

  20. AVNG system demonstration

    SciTech Connect

    Thron, Jonathan Louis; Mac Arthur, Duncan W; Kondratov, Sergey; Livke, Alexander; Razinkov, Sergey

    2010-01-01

    An attribute measurement system (AMS) measures a number of unclassified attributes of potentially classified material. By only displaying these unclassified results as red or green lights, the AMS protects potentially classified information while still generating confidence in the measurement result. The AVNG implementation that we describe is an AMS built by RFNC - VNIIEF in Sarov, Russia. To provide additional confidence, the AVNG was designed with two modes of operation. In the secure mode, potentially classified measurements can be made with only the simple red light/green light display. In the open mode, known unclassified material can be measured with complete display of the information collected from the radiation detectors. The AVNG demonstration, which occurred in Sarov, Russia in June 2009 for a joint US/Russian audience, included exercising both modes of AVNG operation using a number of multi-kg plutonium sources. In addition to describing the demonstration, we will show photographs and/or video taken of AVNG operation.

  1. LIMB Demonstration Project Extension

    SciTech Connect

    Not Available

    1989-11-15

    The basic goal of the Limestone Injection Mitigation Burner (LIMB) demonstration is to extend LIMB technology development to a full- scale application on a representative wall-fired utility boiler. The successful retrofit of LIMB to an existing boiler is expected to demonstrate that (a) reductions of 50 percent or greater in SO{sub x} and NO{sub x} emissions can be achieved at a fraction of the cost of add-on FGD systems, (b) boiler reliability, operability, and steam production can be maintained at levels existing prior to LIMB retrofit, and (c) technical difficulties attributable to LIMB operation, such as additional slagging and fouling, changes in ash disposal requirements, and an increased particulate load, can be resolved in a cost-effective manner. The primary fuel to be used will be an Ohio bituminous coal having a nominal sulfur content of 3 percent or greater.

  2. Chemical Domino Demonstration

    NASA Astrophysics Data System (ADS)

    Alexander, M. Dale

    1998-04-01

    The Chemical Domino Demonstration is both educational and entertaining. It provides an excellent means for a review of chemical concepts at the conclusion of a general chemistry course. This demonstration consists of a number of different chemical reactions occurring in sequence in a Rube Goldberg-type apparatus. These reactions include the reduction of water by an active metal, the oxidation of a moderately active metal by an acid, reduction of metallic ions by a metal of greater activity, acid-base neutralization reactions in solution monitored with indicators, a gas-phase acid-base neutralization reaction, decomposition of a compound, precipitation of an insoluble salt, substitution reactions of coordination complexes, and pyrotechnic oxidation-reduction reactions including a hypergolic oxidation-reduction reaction, an intramolecular oxidation-reduction reaction, and the combustion of a flammable gas.

  3. Automatic lighting controls demonstration

    SciTech Connect

    Rubinstein, F.; Verderber, R.

    1990-03-01

    The purpose of this work was to demonstrate, in a real building situation, the energy and peak demand reduction capabilities of an electronically ballasted lighting control system that can utilize all types of control strategies to efficiently manage lighting. The project has demonstrated that a state-of-the-art electronically ballasted dimmable lighting system can reduce energy and lighting demand by as least 50% using various combinations of control strategies. By reducing light levels over circulation areas (tuning) and reducing after hours light levels to accommodate the less stringent lighting demands of the cleaning crew (scheduling), lighting energy consumption on weekdays was reduced an average of 54% relative to the initial condition. 10 refs., 14 figs., 3 tabs.

  4. Space Fabrication Demonstration System

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The completion of assembly of the beam builder and its first automatic production of truss is discussed. A four bay, hand assembled, roll formed members truss was built and tested to ultimate load. Detail design of the fabrication facility (beam builder) was completed and designs for subsystem debugging are discussed. Many one bay truss specimens were produced to demonstrate subsystem operation and to detect problem areas.

  5. The Blowgun Demonstration Experiment

    ERIC Educational Resources Information Center

    Tsukamoto, Koji; Uchino, Masanori

    2008-01-01

    We have found that a simple demonstration experiment using a match or a cotton swab and a drinking straw or an acrylic pipe serves as an effective introduction to dynamics. The most basic apparatus has a cotton swab serving as a dart and the straw as the blowgun. When blown from a starting point near the exit end of the straw, the cotton swab does…

  6. The Majorana Demonstrator

    SciTech Connect

    Aguayo, Estanislao; Fast, James E.; Hoppe, Eric W.; Keillor, Martin E.; Kephart, Jeremy D.; Kouzes, Richard T.; LaFerriere, Brian D.; Merriman, Jason H.; Orrell, John L.; Overman, Nicole R.; Avignone, Frank T.; Back, Henning O.; Combs, Dustin C.; Leviner, L.; Young, A.; Barabash, Alexander S.; Konovalov, S.; Vanyushin, I.; Yumatov, Vladimir; Bergevin, M.; Chan, Yuen-Dat; Detwiler, Jason A.; Loach, J. C.; Martin, R. D.; Poon, Alan; Prior, Gersende; Vetter, Kai; Bertrand, F.; Cooper, R. J.; Radford, D. C.; Varner, R. L.; Yu, Chang-Hong; Boswell, M.; Elliott, S.; Gehman, Victor M.; Hime, Andrew; Kidd, M. F.; LaRoque, B. H.; Rielage, Keith; Ronquest, M. C.; Steele, David; Brudanin, V.; Egorov, Viatcheslav; Gusey, K.; Kochetov, Oleg; Shirchenko, M.; Timkin, V.; Yakushev, E.; Busch, Matthew; Esterline, James H.; Tornow, Werner; Christofferson, Cabot-Ann; Horton, Mark; Howard, S.; Sobolev, V.; Collar, J. I.; Fields, N.; Creswick, R.; Doe, Peter J.; Johnson, R. A.; Knecht, A.; Leon, Jonathan D.; Marino, Michael G.; Miller, M. L.; Robertson, R. G. H.; Schubert, Alexis G.; Wolfe, B. A.; Efremenko, Yuri; Ejiri, H.; Hazama, R.; Nomachi, Masaharu; Shima, T.; Finnerty, P.; Fraenkle, Florian; Giovanetti, G. K.; Green, M.; Henning, Reyco; Howe, M. A.; MacMullin, S.; Phillips, D.; Snavely, Kyle J.; Strain, J.; Vorren, Kris R.; Guiseppe, Vincente; Keller, C.; Mei, Dong-Ming; Perumpilly, Gopakumar; Thomas, K.; Zhang, C.; Hallin, A. L.; Keeter, K.; Mizouni, Leila; Wilkerson, J. F.

    2011-09-03

    A brief review of the history and neutrino physics of double beta decay is given. A description of the MAJORANA DEMONSTRATOR research and development program, including background reduction techniques, is presented in some detail. The application of point contact (PC) detectors to the experiment is discussed, including the effectiveness of pulse shape analysis. The predicted sensitivity of a PC detector array enriched to 86% to 76Ge is given.

  7. Projectile Motion Demonstration

    NASA Astrophysics Data System (ADS)

    Graf, Erlend H.

    2008-12-01

    For a recent lecture, I went to our apparatus stock room and took out our venerable Sargent-Welch projectile apparatus that demonstrates that a dropped ball and a horizontally launched ball hit the floor at the same time, if they are simultaneously released. A problem with this apparatus is that its small size makes it difficult for a large class to see what is going on. Furthermore, the projectiles are ball bearings, which tend to roll under chairs, benches, etc.

  8. Carbohydrate Dehydration Demonstrations

    NASA Astrophysics Data System (ADS)

    Dolson, David A.; Battino, Rubin; Letcher, Trevor M.; Pegel, K. H.; Revaprasadu, N.

    1995-10-01

    The "charring reaction" of a carbohydrate with concentrated H2SO4 is a demonstration of the dehydrating power of H2SO4. In this paper several sugars and supermarket carbohydrates are systematically studied with respect to size of particles, addition of water, and amount of H2SO4 added. The results are tabulated as to the amount of time to blackening and to the attainment of a particular volume of the charred material. Detailed safety precautions are included.

  9. Joined Beryllium Mirror Demonstrator

    NASA Technical Reports Server (NTRS)

    Stahl, H. Philip; Parsonage, Tom; Burdine, Robert (Technical Monitor)

    2001-01-01

    Fabrications of large Beryllium optical components are fundamentally limited by available facility capabilities. To overcome this limitation, NASA funded Brush Wellman Corp to study a Be joining process. Four 76 mm diameters samples and a 0.5 mm diameter Joined Beryllium Mirror Demonstrator (JBMD) were fabricated. This presentation will review the fabrication of these samples and summarize the results of their cryogenic testing at MSFCs XRCF.

  10. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Kolb, Doris

    1988-01-01

    Describes two oscillating reactions: the Briggs-Raucher reaction using H202, KIO3, malonic acid, and MnSO4 which changes from yellow to blue, and the Belousov-Zhabotinskii reaction uses NaBrO3, NaBr, malonic acid, and ferroin solution and changes from red to blue. Includes a third color demonstration on the six oxidation states of manganese. (MVL)

  11. Lunar Water Resource Demonstration

    NASA Technical Reports Server (NTRS)

    Muscatello, Anthony C.

    2008-01-01

    In cooperation with the Canadian Space Agency, the Northern Centre for Advanced Technology, Inc., the Carnegie-Mellon University, JPL, and NEPTEC, NASA has undertaken the In-Situ Resource Utilization (ISRU) project called RESOLVE. This project is a ground demonstration of a system that would be sent to explore permanently shadowed polar lunar craters, drill into the regolith, determine what volatiles are present, and quantify them in addition to recovering oxygen by hydrogen reduction. The Lunar Prospector has determined these craters contain enhanced hydrogen concentrations averaging about 0.1%. If the hydrogen is in the form of water, the water concentration would be around 1%, which would translate into billions of tons of water on the Moon, a tremendous resource. The Lunar Water Resource Demonstration (LWRD) is a part of RESOLVE designed to capture lunar water and hydrogen and quantify them as a backup to gas chromatography analysis. This presentation will briefly review the design of LWRD and some of the results of testing the subsystem. RESOLVE is to be integrated with the Scarab rover from CMIJ and the whole system demonstrated on Mauna Kea on Hawaii in November 2008. The implications of lunar water for Mars exploration are two-fold: 1) RESOLVE and LWRD could be used in a similar fashion on Mars to locate and quantify water resources, and 2) electrolysis of lunar water could provide large amounts of liquid oxygen in LEO, leading to lower costs for travel to Mars, in addition to being very useful at lunar outposts.

  12. Xpa knockout mice.

    PubMed

    de Vries, A; van Steeg, H

    1996-10-01

    The xeroderma pigmentosum group A correcting (XPA) gene encodes a DNA binding zinc-finger protein that recognizes DNA damage. As such the XPA protein participates in the initial step of the process of nucleotide excision repair. The multicomponent nucleotide excision repair pathway is one of the most thoroughly studied mechanisms that defends both eukaryotic and prokaryotic cells against the deleterious effects of UV-B and several chemical components. In the absence of nucleotide excision repair common cellular processes like transcription and replication are disturbed by persisting (unrepaired) DNA lesions (adducts), which may lead to the accumulation of gene mutations and ultimately to cancer. Xeroderma pigmentosum patients have a > 2000 fold increased risk to develop skin cancer at sun-exposed areas. Here we describe that XPA-deficient transgenic mice show features that mimic the phenotype found in humans. Furthermore, the possible use of Xpa- and other nucleotide excision repair deficient mice in cancer research will be outlined in more detail. PMID:9110400

  13. The MICE Particle Identification System

    NASA Astrophysics Data System (ADS)

    Bogomilov, M.; MICE Collaboration

    2011-06-01

    The Muon Ionization Cooling Experiment (MICE) at the ISIS accelerator located at the Rutherford Appleton Laboratory, UK, will be the first experiment to study muon cooling at high precision. Demonstration of muon ionization cooling is a major technological step towards the construction of a neutrino factory or a muon collider. A muon beam is produced via pion decay in the MICE beam line within a range of emittances and momenta. Muon purity is assured by a system of detectors for particle identification (PID). We describe briefly the PID system here.

  14. TRW utility demonstration unit

    SciTech Connect

    Not Available

    1990-01-01

    The TRW Advanced Entrained Coal Combustor Demonstration Project consists of retrofitting Orange and Rockland (O R) Utility Corporation's Lovett Plant Unit No. 3 with four (4) slagging combustors which will allow the gas/oil unit to fire 2.5% sulfur coal. The slagging combustor process will provide NO{sub x} and SO{sub x} emissions that meet NSPS and New York State Environmental Standards. During this report period, activity continued to address the total program funding shortfall. Ideas and responsibilities for further evaluation have been put forward to reduce the shortfall. In addition, an effort aimed at gaining additional program sponsorships, was initiated.

  15. NAVAJO ELECTRIFICATION DEMONSTRATION PROJECT

    SciTech Connect

    Terry W. Battiest

    2008-06-11

    The Navajo Electrification Demonstration Project (NEDP) is a multi-year project which addresses the electricity needs of the unserved and underserved Navajo Nation, the largest American Indian tribe in the United States. The program serves to cumulatively provide off-grid electricty for families living away from the electricty infrastructure, line extensions for unserved families living nearby (less than 1/2 mile away from) the electricity, and, under the current project called NEDP-4, the construction of a substation to increase the capacity and improve the quality of service into the central core region of the Navajo Nation.

  16. Demonstrating induced recharge

    SciTech Connect

    Caswell, B. )

    1990-03-01

    This paper describes an attempt by a New England community to explore for an aquifer that would yield 1 million gallons of ground water per day. After the discovery of a glacial sand and gravel aquifer, a demonstration of a hydraulic coupling between the aquifer and an adjacent stream was undertaken. This connection was needed to maintain recharge capacity of the well. The paper goes on to describe the techniques needed and used to determine the induced recharge caused by drawdown in these test wells.

  17. Exploration Medical System Demonstration

    NASA Technical Reports Server (NTRS)

    Rubin, D. A.; Watkins, S. D.

    2014-01-01

    BACKGROUND: Exploration class missions will present significant new challenges and hazards to the health of the astronauts. Regardless of the intended destination, beyond low Earth orbit a greater degree of crew autonomy will be required to diagnose medical conditions, develop treatment plans, and implement procedures due to limited communications with ground-based personnel. SCOPE: The Exploration Medical System Demonstration (EMSD) project will act as a test bed on the International Space Station (ISS) to demonstrate to crew and ground personnel that an end-to-end medical system can assist clinician and non-clinician crew members in optimizing medical care delivery and data management during an exploration mission. Challenges facing exploration mission medical care include limited resources, inability to evacuate to Earth during many mission phases, and potential rendering of medical care by non-clinicians. This system demonstrates the integration of medical devices and informatics tools for managing evidence and decision making and can be designed to assist crewmembers in nominal, non-emergent situations and in emergent situations when they may be suffering from performance decrements due to environmental, physiological or other factors. PROJECT OBJECTIVES: The objectives of the EMSD project are to: a. Reduce or eliminate the time required of an on-orbit crew and ground personnel to access, transfer, and manipulate medical data. b. Demonstrate that the on-orbit crew has the ability to access medical data/information via an intuitive and crew-friendly solution to aid in the treatment of a medical condition. c. Develop a common data management framework that can be ubiquitously used to automate repetitive data collection, management, and communications tasks for all activities pertaining to crew health and life sciences. d. Ensure crew access to medical data during periods of restricted ground communication. e. Develop a common data management framework that

  18. Space Research Benefits Demonstrated

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Angie Jackman, a NASA project manager in microgravity research, demonstrates the enhanced resilience of undercooled metal alloys as compared to conventional alloys. Experiments aboard the Space Shuttle helped scientists refine their understanding of the physical properties of certain metal alloys when undercooled (i.e., kept liquid below their normal solidification temperature). This new knowledge then allowed scientists to modify a terrestrial production method so they can now make limited quantities marketed under the Liquid Metal trademark. The exhibit was a part of the NASA outreach activity at AirVenture 2000 sponsored by the Experimental Aircraft Association in Oshkosh, WI.

  19. The Blowgun Demonstration Experiment

    NASA Astrophysics Data System (ADS)

    Tsukamoto, Koji; Uchino, Masanori

    2008-09-01

    We have found that a simple demonstration experiment using a match or a cotton swab and a drinking straw or an acrylic pipe serves as an effective introduction to dynamics. The most basic apparatus has a cotton swab serving as a dart and the straw as the blowgun. When blown from a starting point near the exit end of the straw, the cotton swab does not fly a significant distance. When the starting point is closer to the lips, the straw is projected 2-3 m. If two or three straws are connected to form a longer blowgun, the cotton swab flies even farther.

  20. Lymphatic dysfunction in transgenic mice expressing KSHV k-cyclin under the control of the VEGFR-3 promoter.

    PubMed

    Sugaya, Makoto; Watanabe, Takahiro; Yang, Aparche; Starost, Matthew F; Kobayashi, Hisataka; Atkins, April M; Borris, Debra L; Hanan, Elisabeth A; Schimel, Daniel; Bryant, Mark A; Roberts, Nicole; Skobe, Mihaela; Staskus, Katherine A; Kaldis, Philipp; Blauvelt, Andrew

    2005-03-15

    Kaposi sarcoma-associated herpesvirus (KSHV) infects endothelial cells within KS tumors, and these cells express the KSHV latent-cycle gene k-cyclin (kCYC) as well as vascular endothelial growth factor receptor 3 (VEGFR-3), a marker for lymphatic endothelium. To further understand KSHV-mediated pathogenesis, we generated transgenic mice expressing kCYC under the control of the VEGFR-3 promoter. kCYC mRNA and functional protein expression within tissue correlated with VEGFR-3 expression and were most abundantly detected within lung tissue. Clinically, most transgenic mice died within 6 months of age secondary to progressive accumulation of chylous pleural fluid. In skin, edema was detected by magnetic resonance imaging and mice demonstrated persistent erythema of the ears following trauma. Histologically, erythematous skin showed extravasation of erythrocytes and accumulation of erythrocytes within lymphatic lumens. In addition, lymphatic drainage of injected contrast dyes was markedly impaired in transgenic mice. Karyomegaly, a feature observed in kCYC-expressing cells in vitro, was detected in many tissues, and selectively occurred within lymphatic endothelial cells expressing kCYC mRNA by in situ hybridization. In summary, kCYC expression within VEGFR-3+ cells of mice causes marked impairment of lymphatic function. kCYC may contribute to the development of certain clinical and histologic features of KS, including localized edema and retention of extravasated erythrocytes within KS tumors.

  1. Solar Thermal Demonstration Project

    SciTech Connect

    Biesinger, K; Cuppett, D; Dyer, D

    2012-01-30

    HVAC Retrofit and Energy Efficiency Upgrades at Clark High School, Las Vegas, Nevada The overall objectives of this project are to increase usage of alternative/renewable fuels, create a better and more reliable learning environment for the students, and reduce energy costs. Utilizing the grant resources and local bond revenues, the District proposes to reduce electricity consumption by installing within the existing limited space, one principal energy efficient 100 ton adsorption chiller working in concert with two 500 ton electric chillers. The main heating source will be primarily from low nitrogen oxide (NOX), high efficiency natural gas fired boilers. With the use of this type of chiller, the electric power and cost requirements will be greatly reduced. To provide cooling to the information technology centers and equipment rooms of the school during off-peak hours, the District will install water source heat pumps. In another measure to reduce the cooling requirements at Clark High School, the District will replace single pane glass and metal panels with Kalwall building panels. An added feature of the Kalwall system is that it will allow for natural day lighting in the student center. This system will significantly reduce thermal heat/cooling loss and control solar heat gain, thus delivering significant savings in heating ventilation and air conditioning (HVAC) costs.

  2. Vortex Apparatus and Demonstrations

    NASA Astrophysics Data System (ADS)

    Shakerin, Said

    2010-05-01

    Vortex flow, from millimeter to kilometer in scale, is important in many scientific and technological areas. Examples are seen in water strider locomotion, from industrial pipe flow (wastewater treatment) to air traffic control (safe distance between aircrafts on a runway ready for takeoff) to atmospheric studies.2-5 In this paper, we focus on a particular vortex known as bathtub vortex (BTV). It occurs when water is drained from a hole at the bottom of a container such as a bathtub or a sink under the action of gravity. The vortex has a funnel shape with a central air core, resembling a tornado. We have designed a portable apparatus to demonstrate bathtub vortex on a continual basis. The apparatus consists of a clear cylinder supported by a frame over a water reservoir and a submersible pump. Young and old have been equally amazed by watching the demonstrations at various public presentations held at the University of the Pacific recently. With material cost of less than 100, the apparatus can be easily fabricated and used at other universities. With a short set-up time, it is an ideal device for promoting science to the general public, and it can be used to enhance lectures in physics courses as well.

  3. PFBC Utility Demonstration Project

    SciTech Connect

    Not Available

    1992-11-01

    This report provides a summary of activities by American Electric Power Service Corporation during the first budget period of the PFBC Utility Demonstration Project. In April 1990, AEP signed a Cooperative Agreement with the US Department of Energy to repower the Philip Sporn Plant, Units 3 4 in New Haven, West Virginia, with a 330 KW PFBC plant. The purpose of the program was to demonstrate and verify PFBC in a full-scale commercial plant. The technical and cost baselines of the Cooperative Agreement were based on a preliminary engineering and design and a cost estimate developed by AEP subsequent to AEP's proposal submittal in May 1988, and prior to the signing of the Cooperative Agreement. The Statement of Work in the first budget period of the Cooperative Agreement included a task to develop a preliminary design and cost estimate for erecting a Greenfield plant and to conduct a comparison with the repowering option. The comparative assessment of the options concluded that erecting a Greenfield plant rather than repowering the existing Sporn Plant could be the technically and economically superior alternative. The Greenfield plant would have a capacity of 340 MW. The ten additional MW output is due to the ability to better match the steam cycle to the PFBC system with a new balance of plant design. In addition to this study, the conceptual design of the Sporn Repowering led to several items which warranted optimization studies with the goal to develop a more cost effective design.

  4. Oral Resveratrol Prevents Osteoarthritis Progression in C57BL/6J Mice Fed a High-Fat Diet

    PubMed Central

    Gu, Hailun; Li, Keyu; Li, Xingyao; Yu, Xiaolu; Wang, Wei; Ding, Lifeng; Liu, Li

    2016-01-01

    The effects of resveratrol on osteoarthritis (OA) pathogenesis have been demonstrated in vitro and in animal models employing intra-articular injections. However, the potential for oral resveratrol supplements to mediate protective effects on OA have not been examined. Therefore, the aim of the present study was to investigate the potential anti-OA effects of oral resveratrol on mice fed a high-fat diet (HFD). C57BL/6J male mice were fed either a standard diet or a HFD, and a subset of the latter also received varying doses of resveratrol. Twelve weeks later, all of the animals were sacrificed and knee joints were evaluated with histological, immunohistochemical, and TUNEL analyses. Mice that received a HFD had significantly greater body weights than the control mice and also exhibited features consistent with knee OA. The mice that received a HFD in combination with low, intermediate, or high doses of resveratrol were only slightly heavier than the control mice at the end of 12 weeks. Quantitative histological assessments indicated that resveratrol treatment partly recovered joint structure in the mice that received a HFD, while high doses of resveratrol prevented the degradation of type II collagen into C-telopeptide of type II collagen (CTX-II) and retained type II collagen expression in cartilage. Furthermore, TUNEL analyses revealed a reduction in chondrocyte apoptosis in the resveratrol-treated mice compared with the HFD mice. Thus, oral resveratrol appears to exert anti-OA effects in a mouse model of HFD-induced OA, thereby highlighting the potential preventive and therapeutic value of administering resveratrol for obesity-associated OA. PMID:27104565

  5. Smart Grid Demonstration Project

    SciTech Connect

    Miller, Craig; Carroll, Paul; Bell, Abigail

    2015-03-11

    The National Rural Electric Cooperative Association (NRECA) organized the NRECA-U.S. Department of Energy (DOE) Smart Grid Demonstration Project (DE-OE0000222) to install and study a broad range of advanced smart grid technologies in a demonstration that spanned 23 electric cooperatives in 12 states. More than 205,444 pieces of electronic equipment and more than 100,000 minor items (bracket, labels, mounting hardware, fiber optic cable, etc.) were installed to upgrade and enhance the efficiency, reliability, and resiliency of the power networks at the participating co-ops. The objective of this project was to build a path for other electric utilities, and particularly electrical cooperatives, to adopt emerging smart grid technology when it can improve utility operations, thus advancing the co-ops’ familiarity and comfort with such technology. Specifically, the project executed multiple subprojects employing a range of emerging smart grid technologies to test their cost-effectiveness and, where the technology demonstrated value, provided case studies that will enable other electric utilities—particularly electric cooperatives— to use these technologies. NRECA structured the project according to the following three areas: Demonstration of smart grid technology; Advancement of standards to enable the interoperability of components; and Improvement of grid cyber security. We termed these three areas Technology Deployment Study, Interoperability, and Cyber Security. Although the deployment of technology and studying the demonstration projects at coops accounted for the largest portion of the project budget by far, we see our accomplishments in each of the areas as critical to advancing the smart grid. All project deliverables have been published. Technology Deployment Study: The deliverable was a set of 11 single-topic technical reports in areas related to the listed technologies. Each of these reports has already been submitted to DOE, distributed to co-ops, and

  6. Suppression effects in feature-based attention

    PubMed Central

    Wang, Yixue; Miller, James; Liu, Taosheng

    2015-01-01

    Attending to a feature enhances visual processing of that feature, but it is less clear what occurs to unattended features. Single-unit recording studies in middle temporal (MT) have shown that neuronal modulation is a monotonic function of the difference between the attended and neuron's preferred direction. Such a relationship should predict a monotonic suppressive effect in psychophysical performance. However, past research on suppressive effects of feature-based attention has remained inconclusive. We investigated the suppressive effect for motion direction, orientation, and color in three experiments. We asked participants to detect a weak signal among noise and provided a partially valid feature cue to manipulate attention. We measured performance as a function of the offset between the cued and signal feature. We also included neutral trials where no feature cues were presented to provide a baseline measure of performance. Across three experiments, we consistently observed enhancement effects when the target feature and cued feature coincided and suppression effects when the target feature deviated from the cued feature. The exact profile of suppression was different across feature dimensions: Whereas the profile for direction exhibited a “rebound” effect, the profiles for orientation and color were monotonic. These results demonstrate that unattended features are suppressed during feature-based attention, but the exact suppression profile depends on the specific feature. Overall, the results are largely consistent with neurophysiological data and support the feature-similarity gain model of attention. PMID:26067533

  7. Progressive Retinal Degeneration and Accumulation of Autofluorescent Lipopigments in Progranulin Deficient Mice

    PubMed Central

    Hafler, Brian P.; Klein, Zoe A.; Zhou, Z. Jimmy; Strittmatter, Stephen M.

    2014-01-01

    Prior investigations have shown that patients with neuronal ceroid lipofuscinosis (NCL) develop neurodegeneration characterized by vision loss, motor dysfunction, seizures, and often early death. Neuropathological analysis of patients with NCL shows accumulation of intracellular autofluorescent storage material, lipopigment, throughout neurons in the central nervous system including in the retina. A recent study of a sibling pair with adult onset NCL and retinal degeneration showed linkage to the region of the progranulin (GRN) locus and a homozygous mutation was demonstrated in GRN. In particular, the sibling pair with a mutation in GRN developed retinal degeneration and optic atrophy. This locus for this form of adult onset neuronal ceroid lipofuscinosis was designated neuronal ceroid lipofuscinosis-11 (CLN11). Based on these clinical observations, we wished to determine whether Grn-null mice develop accumulation of autofluorescent particles and retinal degeneration. Retinas of both wild-type and Progranulin deficient mice were examined by immunostaining and autofluorescence. Accumulation of autofluorescent material was present in Progranulin deficient mice at 12 months. Degeneration of multiple classes of neurons including photoreceptors and retinal ganglion cells was noted in mice at 12 and 18 months. Our data shows that Grn−/− mice develop degenerative pathology similar to features of human CLN11. PMID:25234724

  8. Cerebellar-Dependent Expression of Motor Learning during Eyeblink Conditioning in Head-Fixed Mice

    PubMed Central

    Heiney, Shane A.; Wohl, Margot P.; Chettih, Selmaan N.; Ruffolo, Luis I.

    2014-01-01

    Eyeblink conditioning in restrained rabbits has served as an excellent model of cerebellar-dependent motor learning for many decades. In mice, the role of the cerebellum in eyeblink conditioning is less clear and remains controversial, partly because learning appears to engage fear-related circuits and lesions of the cerebellum do not abolish the learned behavior completely. Furthermore, experiments in mice are performed using freely moving systems, which lack the stability necessary for mapping out the essential neural circuitry with electrophysiological approaches. We have developed a novel apparatus for eyeblink conditioning in head-fixed mice. Here, we show that the performance of mice in our apparatus is excellent and that the learned behavior displays two hallmark features of cerebellar-dependent eyeblink conditioning in rabbits: (1) gradual acquisition; and (2) adaptive timing of conditioned movements. Furthermore, we use a combination of pharmacological inactivation, electrical stimulation, single-unit recordings, and targeted microlesions to demonstrate that the learned behavior is completely dependent on the cerebellum and to pinpoint the exact location in the deep cerebellar nuclei that is necessary. Our results pave the way for using eyeblink conditioning in head-fixed mice as a platform for applying next-generation genetic tools to address molecular and circuit-level questions about cerebellar function in health and disease. PMID:25378152

  9. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    PubMed

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia.

  10. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    PubMed

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia. PMID:26965573

  11. Genetically determined cholinergic deficiency in the forebrain of C57BL/6 mice.

    PubMed

    Bentivoglio, A R; Altavista, M C; Granata, R; Albanese, A

    1994-02-21

    This study demonstrates that a deficiency of forebrain cholinergic neurons occurs in C57BL/6 (C57) mice, a strain characterized by poor learning capabilities. The brains of 21-day-old and 18-week-old C57 and DBA/2 (DBA) mice were studied by means of acetylcholinesterase (AChE) histochemistry and of choline acetyltransferase (ChAT) immunocytochemistry. Computer-assisted image analysis was performed on sections through the medial septum, the diagonal band of Broca, the basal nucleus of Meynert and the neostriatum. As compared to the DBA strain, C57 mice had a reduced number of forebrain cholinergic neurons. This feature was present at the age of 21 days and persisted to 18 weeks. Between-strain variations in the density of neurons were more obvious in ChAT-stained material than in AChE-stained sections. These data show that C57 mice can be regarded as a genetic mutant, whose phenotype is characterized by a reduced number of forebrain cholinergic neurons and by cognitive abnormalities. C57 mice represent a valuable model for studying the influence of genetic factors on central nervous system cholinergic mechanisms and the effects of genetically determined cholinergic deficiency on behavior and learning.

  12. Deficiency of X-Linked Protein Kinase Nrk during Pregnancy Triggers Breast Tumor in Mice.

    PubMed

    Yanagawa, Takayo; Denda, Kimitoshi; Inatani, Takuya; Fukushima, Toshiaki; Tanaka, Toshiaki; Kumaki, Nobue; Inagaki, Yutaka; Komada, Masayuki

    2016-10-01

    The onset and/or growth of breast tumor are controlled, at least in part, by estrogen. Therefore, to prevent the development of breast tumor, estrogen-dependent proliferation of mammary epithelial cells during pregnancy needs to be suppressed once the mammary gland is fully developed to enable lactation. However, the underlying molecular mechanisms remain unknown. Nrk is an X-linked protein serine/threonine kinase in the germinal center kinase family. Herein, we demonstrate a frequent occurrence of breast tumors in homozygous and heterozygous Nrk mutant mice that have experienced pregnancy/parturition. The tumors never developed in the mutant mice without a history of pregnancy/parturition. They exhibited histopathological features of noninvasive tubular adenocarcinoma, and expressed estrogen receptor α. At late gestation when estrogen receptor α expression was significantly reduced in the wild-type mammary gland, grossly normal mammary glands in the pregnant Nrk mutant mice occasionally contained hyperplastic foci continuously expressing the receptor. Consistently, Nrk expression was induced in the wild-type mammary gland at this period of pregnancy. On the other hand, the pregnant Nrk mutant mice also showed elevated blood estrogen levels at late gestation. We suggest that Nrk suppresses the excessive proliferation of mammary epithelial cells during pregnancy, and the impairment of this regulatory system leads to frequent occurrence of breast tumor in Nrk mutant mice. PMID:27634343

  13. Cerebellar-dependent expression of motor learning during eyeblink conditioning in head-fixed mice.

    PubMed

    Heiney, Shane A; Wohl, Margot P; Chettih, Selmaan N; Ruffolo, Luis I; Medina, Javier F

    2014-11-01

    Eyeblink conditioning in restrained rabbits has served as an excellent model of cerebellar-dependent motor learning for many decades. In mice, the role of the cerebellum in eyeblink conditioning is less clear and remains controversial, partly because learning appears to engage fear-related circuits and lesions of the cerebellum do not abolish the learned behavior completely. Furthermore, experiments in mice are performed using freely moving systems, which lack the stability necessary for mapping out the essential neural circuitry with electrophysiological approaches. We have developed a novel apparatus for eyeblink conditioning in head-fixed mice. Here, we show that the performance of mice in our apparatus is excellent and that the learned behavior displays two hallmark features of cerebellar-dependent eyeblink conditioning in rabbits: (1) gradual acquisition; and (2) adaptive timing of conditioned movements. Furthermore, we use a combination of pharmacological inactivation, electrical stimulation, single-unit recordings, and targeted microlesions to demonstrate that the learned behavior is completely dependent on the cerebellum and to pinpoint the exact location in the deep cerebellar nuclei that is necessary. Our results pave the way for using eyeblink conditioning in head-fixed mice as a platform for applying next-generation genetic tools to address molecular and circuit-level questions about cerebellar function in health and disease.

  14. HSP27 Alleviates Cardiac Aging in Mice via a Mechanism Involving Antioxidation and Mitophagy Activation

    PubMed Central

    Lin, Shenglan; Wang, Yana; Zhang, Xiaojin; Kong, Qiuyue; Li, Chuanfu; Li, Yuehua; Ding, Zhengnian

    2016-01-01

    Aging-induced cardiac dysfunction is a prominent feature of cardiac aging. Heat shock protein 27 (HSP27) protects cardiac function against ischemia or chemical challenge. We hypothesized that HSP27 attenuates cardiac aging. Transgenic (Tg) mice with cardiac-specific expression of the HSP27 gene and wild-type (WT) littermates were employed in the experiments. Echocardiography revealed a significant decline in the cardiac function of old WT mice compared with young WT mice. In striking contrast, the aging-induced impairment of cardiac function was attenuated in old Tg mice compared with old WT mice. Levels of cardiac aging markers were lower in old Tg mouse hearts than in old WT mouse hearts. Less interstitial fibrosis and lower contents of reactive oxygen species and ubiquitin-conjugated proteins were detected in old Tg hearts than in old WT hearts. Furthermore, old Tg hearts demonstrated lower accumulation of LC3-II and p62 than old WT hearts. Levels of Atg13, Vps34, and Rab7 were also higher in old Tg hearts than in old WT hearts. Additionally, old Tg hearts had higher levels of PINK1 and Parkin than old WT hearts, suggesting that mitophagy was activated in old Tg hearts. Taken together, HSP27 alleviated cardiac aging and this action involved antioxidation and mitophagy activation. PMID:27110324

  15. Teaching Chemistry through Observation--The Exploding Can Demonstration.

    ERIC Educational Resources Information Center

    Golestaneh, Kamran

    1998-01-01

    Describes procedures for a demonstration that features an exploding can. This demonstration prompts students to critically analyze the release of energy in an exothermic reaction, the work done in such a reaction, and the enthalpy. (DDR)

  16. Electrodynamic Dust Shield Demonstrator

    NASA Technical Reports Server (NTRS)

    Stankie, Charles G.

    2013-01-01

    The objective of the project was to design and manufacture a device to demonstrate a new technology developed by NASA's Electrostatics and Surface Physics Laboratory. The technology itself is a system which uses magnetic principles to remove regolith dust from its surface. This project was to create an enclosure that will be used to demonstrate the effectiveness of the invention to The Office of the Chief Technologist. ONE of the most important challenges of space exploration is actually caused by something very small and seemingly insignificant. Dust in space, most notably on the moon and Mars, has caused many unforeseen issues. Dirt and dust on Earth, while a nuisance, can be easily cleaned and kept at bay. However, there is considerably less weathering and erosion in space. As a result, the microscopic particles are extremely rough and abrasive. They are also electrostatically charged, so they cling to everything they make contact with. This was first noted to be a major problem during the Apollo missions. Dust would stick to the spacesuits, and could not be wiped off as predicted. Dust was brought back into the spacecraft, and was even inhaled by astronauts. This is a major health hazard. Atmospheric storms and other events can also cause dust to coat surfaces of spacecraft. This can cause abrasive damage to the craft. The coating can also reduce the effectiveness of thermal insulation and solar panels.' A group of engineers at Kennedy Space Center's Electrostatics and Surface Physics Laboratory have developed a new technology, called the Electrodynamic Dust Shield, to help alleviate these problems. It is based off of the electric curtain concept developed at NASA in 1967. "The EDS is an active dust mitigation technology that uses traveling electric fields to transport electrostatically charged dust particles along surfaces. To generate the traveling electric fields, the EDS consists of a multilayer dielectric coating with an embedded thin electrode grid

  17. Transgenic mice overexpressing reticulon 3 develop neuritic abnormalities

    PubMed Central

    Hu, Xiangyou; Shi, Qi; Zhou, Xiangdong; He, Wanxia; Yi, Hong; Yin, Xinghua; Gearing, Marla; Levey, Allan; Yan, Riqiang

    2007-01-01

    Dystrophic neurites are swollen dendrites or axons recognizable near amyloid plaques as a part of important pathological feature of Alzheimer's disease (AD). We report herein that reticulon 3 (RTN3) is accumulated in a distinct population of dystrophic neurites named as RTN3 immunoreactive dystrophic neurites (RIDNs). The occurrence of RIDNs is concomitant with the formation of high-molecular-weight RTN3 aggregates in brains of AD cases and mice expressing mutant APP. Ultrastructural analysis confirms accumulation of RTN3-containing aggregates in RIDNs. It appears that the protein level of RTN3 governs the formation of RIDNs because transgenic mice expressing RTN3 will develop RIDNs, initially in the hippocampal CA1 region, and later in other hippocampal and cortical regions. Importantly, we show that the presence of dystrophic neurites in Tg-RTN3 mice causes impairments in spatial learning and memory, as well as synaptic plasticity, implying that RIDNs potentially contribute to AD cognitive dysfunction. Together, we demonstrate that aggregation of RTN3 contributes to AD pathogenesis by inducing neuritic dystrophy. Inhibition of RTN3 aggregation is likely a therapeutic approach for reducing neuritic dystrophy. PMID:17476306

  18. Demonstration of microfiltration technology

    SciTech Connect

    Martin, J.F.; Topudurti, K.; Labunski, S.

    1991-01-01

    The U.S. Environmental Protection Agency, under the Superfund Innovative Technology Evaluation (SITE) program in cooperation with E.I. DuPont de Nemours and Company, Inc. (DuPont) and the Oberlin Filter Company (Oberlin), undertook a field demonstration project to evaluate microfiltration technology for removal of zinc and suspended solids from wastewater. The microfiltration system utilized DuPont's Tyvek T-980 membrane filter media in conjunction with the Oberlin automatic pressure filter. The project was undertaken at the Palmerton Zinc Superfund site in April, 1990. Analysis of the treated filtrate indicated that the system removed precipitated zinc and other suspended solids at an efficiency greater than 99.9 percent. (Copyright (c) 1991--Air and Waste Management Association.)

  19. Jennings Demonstration PLant

    SciTech Connect

    Russ Heissner

    2010-08-31

    Verenium operated a demonstration plant with a capacity to produce 1.4 million gallons of cellulosic ethanol from agricultural resiues for about two years. During this time, the plant was able to evaluate the technical issues in producing ethanol from three different cellulosic feedstocks, sugar cane bagasse, energy cane, and sorghum. The project was intended to develop a better understanding of the operating parameters that would inform a commercial sized operation. Issues related to feedstock variability, use of hydrolytic enzymes, and the viability of fermentative organisms were evaluated. Considerable success was achieved with pretreatment processes and use of enzymes but challenges were encountered with feedstock variability and fermentation systems. Limited amounts of cellulosic ethanol were produced.

  20. Fusion-power demonstration

    NASA Astrophysics Data System (ADS)

    Henning, C. D.; Logan, B. G.; Carlson, G. A.; Neef, W. S.; Moir, R. W.; Campbell, R. B.; Botwin, R.; Clarkson, I. R.; Carpenter, T. J.

    1983-03-01

    As a satellite to the MARS (Mirror Advanced Reactor Study) a smaller, near-term device has been scoped, called the FPD (Fusion Power Demonstration). Envisioned as the next logical step toward a power reactor, it would advance the mirror fusion program beyond MFTF-B and provide an intermediate step toward commercial fusion power. Breakeven net electric power capability would be the goal such that no net utility power would be required to sustain the operation. A phased implementation is envisioned, with a deuterium checkout first to verify the plasma systems before significant neutron activation has occurred. Major tritium-related facilities would be installed with the second phase to produce sufficient fusion power to supply the recirculating power to maintain the neutral beams, ECRH, magnets and other auxiliary equipment.

  1. Shuttle bay telerobotics demonstration

    NASA Technical Reports Server (NTRS)

    Chun, W.; Cogeos, P.

    1987-01-01

    A demonstration of NASA's robotics capabilities should be a balanced agenda of servicing and assembly tasks combined with selected key technical experiments. The servicing tasks include refueling and module replacement. Refueling involves the mating of special fluid connectors while module replacement requires an array of robotic technologies such as special tools, the arm of a logistics tool, and the precision mating of orbital replacement units to guides. The assembly task involves the construction of a space station node and truss structure. The technological experiments will focus on a few important issues: the precision manipulation of the arms by a teleoperator, the additional use of several mono camera views in conjunction with the stereo system, the use of a general purpose end effector versus a caddy of tools, and the dynamics involved with using a robot with a stabilizer.

  2. The GLORIA demonstrator experiment

    NASA Astrophysics Data System (ADS)

    Majcher, A.; Ćwiek, A.; Ćwiok, M.; Mankiewicz, L.; Zaremba, M.; Żarnecki, A. F.

    2013-10-01

    GLORIA stands for "GLObal Robotic-telescopes Intelligent Array" and it is the first free and open-access network of robotic telescopes on the world. Based on a Web 2.0 environment amateur and professional users can do research in astronomy by observing with robotic telescopes, and/or analyzing data acquired with GLORIA, or from other free access databases. GLORIA project develops free standards, protocols and tools for controlling Robotic Telescopes and related instrumentation, for scheduling observations in the telescope network, and for conducting so-called off-line experiments based on the analysis of astronomical data. This contribution summarizes the implementation and results from the first research level off-line demonstrator experiment implemented in GLORIA, which was base on the data collected with the "Pi of the Sky" telescope in Chile.

  3. Space Research Benefits Demonstrated

    NASA Technical Reports Server (NTRS)

    2000-01-01

    An entranced youngster watches a demonstration of the enhanced resilience of undercooled metal alloys as compared to conventional alloys. Steel bearings are dropped onto plates made of steel, titanium alloy, and zirconium liquid metal alloy, so-called because its molecular structure is amorphous and not crystalline. The bearing on the liquid metal plate bounces for a minute or more longer than on the other plates. Experiments aboard the Space Shuttle helped scientists refine their understanding of the physical properties of certain metal alloys when undercooled (i.e., kept liquid below their normal solidification temperature). This new knowledge then allowed scientists to modify a terrestrial production method so they can now make limited quantities marketed under the Liquid Metal trademark. The exhibit was a part of the NASA outreach activity at AirVenture 2000 sponsored by the Experimental Aircraft Association in Oshkosh, WI.

  4. ARJIS satellite demonstration project

    NASA Astrophysics Data System (ADS)

    Severance, Steve; Williams, Carl

    2005-06-01

    In 2003, the California Space Authority (CSA) was provided funding by the U. S. Congress through the Defense Appropriations Act to develop a project that would demonstrate the U.S. space enterprise capability that would contribute to the effectiveness of those engaged in Homeland Security. The project was given broad latitude in selecting the area of Homeland Security to be addressed and the nature of the space technology to be applied. CSA became aware of a nascent law enforcement data-sharing project in the San Diego region known as the Automated Regional Justice Information System (ARJIS). First developed by the police departments in San Diego, ARJIS is an innovative system that shares criminal justice information among 50 federal, state, and local agencies. ARJIS was completing a pilot project that enabled officers to receive information on handheld computers, which was transmitted wirelessly through cellular networks. The accessed information came from several databases that collectively contained the entire region's crime and arrest reports, traffic citations, and incidents, as well as state and county wants and warrants. The fundamental limitations that plague all cellular-based devices caught CSA's attention and resulted in a cooperative effort to harden the communications link between the patrol officer and critical data. The principal goal of the SATCOM development task was to create a proof-of-concept application that would use SATCOM links to augment the current ARJIS handheld wireless (cellular) capability. The successful technical demonstration and the positive support for satellite communications from the law enforcement community showed that this project filled a need-both for improved information sharing and for highly reliable communications systems.

  5. Transformation During Mixed Pneumococcal Infection of Mice

    PubMed Central

    Conant, James E.; Sawyer, William D.

    1967-01-01

    The recent demonstration by others of transformation during peritoneal infection of mice by two genetically distinct pneumococcal strains supports the notion that transformation may be significant in pneumococcal infection in nature. These studies confirm the occurrence of transformation during mixed infection of mice and define some conditions for its occurrence and its significance. Mice were inoculated with deoxyribonucleic acid (DNA) donor (small type III capsule, low virulence, streptomycin-susceptible) and recipient (noncapsulated, low virulence, streptomycin-resistant) pneumococci, and the bacteremia in mice that died was evaluated. Transformants (large type III capsule, virulent, streptomycin-resistant) were isolated from up to 80% of mice that died from mixed peritoneal infection. Transformation occurred in mice that received donor and recipient 6 hr apart; hence, active DNA was released and competence developed during growth in vivo. Transformation was detected only with progressive infection by both strains, and then transformants were few in the blood and apparently were not responsible for the death of the animals. In doubly infected mice treated with streptomycin, transformation was enhanced; transformants numerically dominated the bacteremia and seemed to cause the death of the mice. Transformation was also demonstrated for the first time during infection of the respiratory tract. PMID:4381631

  6. Elevated plus maze for mice.

    PubMed

    Komada, Munekazu; Takao, Keizo; Miyakawa, Tsuyoshi

    2008-01-01

    Although the mouse genome is now completely sequenced, the functions of most of the genes expressed in the brain are not known. The influence of a given gene on a specific behavior can be determined by behavioral analysis of mutant mice. If a target gene is expressed in the brain, behavioral phenotype of the mutant mice could elucidate the genetic mechanism of normal behaviors. The elevated plus maze test is one of the most widely used tests for measuring anxiety-like behavior. The test is based on the natural aversion of mice for open and elevated areas, as well as on their natural spontaneous exploratory behavior in novel environments. The apparatus consists of open arms and closed arms, crossed in the middle perpendicularly to each other, and a center area. Mice are given access to all of the arms and are allowed to move freely between them. The number of entries into the open arms and the time spent in the open arms are used as indices of open space-induced anxiety in mice. Unfortunately, the procedural differences that exist between laboratories make it difficult to duplicate and compare results among laboratories. Here, we present a detailed movie demonstrating our protocol for the elevated plus maze test. In our laboratory, we have assessed more than 90 strains of mutant mice using the protocol shown in the movie. These data will be disclosed as a part of a public database that we are now constructing. Visualization of the protocol will promote better understanding of the details of the entire experimental procedure, allowing for standardization of the protocols used in different laboratories and comparisons of the behavioral phenotypes of various strains of mutant mice assessed using this test.

  7. Technology Tips: Building Interactive Demonstrations with Sage

    ERIC Educational Resources Information Center

    Murray, Maura

    2013-01-01

    Sage is an open-source software package that can be used in many different areas of mathematics, ranging from algebra to calculus and beyond. One of the most exciting pedagogical features of Sage (http://www.sagemath.org) is its ability to create interacts--interactive examples that can be used in a classroom demonstration or by students in a…

  8. Demonstration of Berry Phase in Optical Spectroscopy

    NASA Technical Reports Server (NTRS)

    Xia, Hui-Rong; Zhang, Yong; Jiang, Hong-Ji; Ding, Liang-En

    1996-01-01

    In this paper we demonstrate that the observed phase shift of the RF signal and its intensity dependence under extreme low pump and probe laser field conditions are dominated by Berry phase effect in optical spectroscopy with good adiabatic approximation, which provides all features' agreements between the theoretical and the experimental results.

  9. Tidd PFBC demonstration project

    SciTech Connect

    Marrocco, M.

    1997-12-31

    The Tidd project was one of the first joint government-industry ventures to be approved by the US Department of Energy (DOE) in its Clean Coal Technology Program. In March 1987, DOE signed an agreement with the Ohio Power Company, a subsidiary of American Electric Power, to refurbish the then-idle Tidd plant on the banks of the Ohio River with advanced pressurized fluidized bed technology. Testing ended after 49 months of operation, 100 individual tests, and the generation of more than 500,000 megawatt-hours of electricity. The demonstration plant has met its objectives. The project showed that more than 95 percent of sulfur dioxide pollutants could be removed inside the advanced boiler using the advanced combustion technology, giving future power plants an attractive alternative to expensive, add-on scrubber technology. In addition to its sulfur removal effectiveness, the plant`s sustained periods of steady-state operation boosted its availability significantly above design projections, heightening confidence that pressurized fluidized bed technology will be a reliable, baseload technology for future power plants. The technology also controlled the release of nitrogen oxides to levels well below the allowable limits set by federal air quality standards. It also produced a dry waste product that is much easier to handle than wastes from conventional power plants and will likely have commercial value when produced by future power plants.

  10. Plug cluster module demonstration

    NASA Technical Reports Server (NTRS)

    Rousar, D. C.

    1978-01-01

    The low pressure, film cooled rocket engine design concept developed during two previous ALRC programs was re-evaluated for application as a module for a plug cluster engine capable of performing space shuttle OTV missions. The nominal engine mixture ratio was 5.5 and the engine life requirements were 1200 thermal cycles and 10 hours total operating life. The program consisted of pretest analysis; engine tests, performed using residual components; and posttest analysis. The pretest analysis indicated that operation of the operation of the film cooled engine at O/F = 5.5 was feasible. During the engine tests, steady state wall temperature and performance measurement were obtained over a range of film cooling flow rates, and the durability of the engine was demonstrated by firing the test engine 1220 times at a nominal performance ranging from 430 - 432 seconds. The performance of the test engine was limited by film coolant sleeve damage which had occurred during previous testing. The post-test analyses indicated that the nominal performance level can be increased to 436 seconds.

  11. Orbital construction demonstration study

    NASA Technical Reports Server (NTRS)

    1976-01-01

    A conceptual design and program plan for an Orbital Construction Demonstration Article (OCDA) was developed that can be used for evaluating and establishing practical large structural assembly operations. A flight plan for initial placement and continued utility is presented as a basic for an entirely new shuttle payload line-item having great future potential benefit for space applications. The OCDA is a three-axis stabilized platform in low-earth orbit with many structural nodals for mounting large construction and fabrication equipments. This equipment would be used to explore methods for constructing the large structures for future missions. The OCDA would be supported at regular intervals by the shuttle. Construction experiments and consumables resupply are performed during shuttle visit periods. A 250 kw solar array provides sufficient power to support the shuttle while attached to the OCDA and to run construction experiments at the same time. Wide band communications with a Telemetry and Data Relay Satellite compatible high gain antenna can be used between shuttle revisits to perform remote controlled, TV assisted construction experiments.

  12. NASA Bioreactor Demonstration System

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Leland W. K. Chung (left), Director, Molecular Urology Therapeutics Program at the Winship Cancer Institute at Emory University, is principal investigator for the NASA bioreactor demonstration system (BDS-05). With him is Dr. Jun Shu, an assistant professor of Orthopedics Surgery from Kuming Medical University China. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. Credit: Emory University.

  13. Renal expression of monocyte chemoattractant protein-1 in lupus autoimmune mice.

    PubMed

    Zoja, C; Liu, X H; Donadelli, R; Abbate, M; Testa, D; Corna, D; Taraboletti, G; Vecchi, A; Dong, Q G; Rollins, B J; Bertani, T; Remuzzi, G

    1997-05-01

    Mononuclear cell infiltration in glomeruli and renal interstitium is a prominent feature of some types of glomerulonephritis, including lupus nephritis. The mechanism(s) underlying monocyte influx into the kidney is not fully understood. Recently, monocyte chemoattractant protein-1 (MCP-1) has been identified as a chemotactic factor involved in the recruitment of monocytes/macrophages in the glomeruli of rats with mesangioproliferative as well as anti-glomerular basement membrane glomerulonephritis. In the study presented here, renal MCP-1 mRNA expression in New Zealand Black x New Zealand White (NZB/W) F1 mice, a model of genetically determined immune complex disease that mimics systemic lupus in humans, was investigated. Northern blot analysis revealed a single 0.7 kb MCP-1 transcript of very low intensity in kidneys from 2-month-old NZB/W mice that had not yet developed proteinuria nor renal damage. Message levels, which increased markedly with the progression of nephritis and in association with mononuclear cell infiltration, were 10- and 15- fold higher in 8-10-month-old mice than in 2-month-old mice. By in situ hybridization, increased expression of MCP-1 mRNA was demonstrated in glomeruli and, even more striking, in tubular epithelial cells. Western blot analysis demonstrated increased expression of MCP-1 protein in kidneys of 10-month-old NZB/W mice, consistent with MCP-1 mRNA data. When NZB/W mice were treated with cyclophosphamide up to 12 months of age, expression of MCP-1 in the renal tissue remained low, the influx of inflammatory cells did not appear, and glomerular and tubular structures remained well preserved. These data suggest that elevated MCP-1 might act as a signal for inflammatory cells to infiltrate the kidney in lupus nephritis.

  14. Kinesthetic Transverse Wave Demonstration

    NASA Astrophysics Data System (ADS)

    Pantidos, Panagiotis; Patapis, Stamatis

    2005-09-01

    This is a variation on the String and Sticky Tape demonstration "The Wave Game," suggested by Ron Edge. A group of students stand side by side, each one holding a card chest high with both hands. The teacher cues the first student to begin raising and lowering his card. When he starts lowering his card, the next student begins to raise his. As succeeding students move their cards up and down, a wave such as that shown in the figure is produced. To facilitate the process, students' motions were synchronized with the ticks of a metronome (without such synchronization it was nearly impossible to generate a satisfactory wave). Our waves typically had a frequency of about 1 Hz and a wavelength of around 3 m. We videotaped the activity so that the students could analyze the motions. The (17-year-old) students had not received any prior instruction regarding wave motion and did not know beforehand the nature of the exercise they were about to carry out. During the activity they were asked what a transverse wave is. Most of them quickly realized, without teacher input, that while the wave propagated horizontally, the only motion of the transmitting medium (them) was vertical. They located the equilibrium points of the oscillations, the crests and troughs of the waves, and identified the wavelength. The teacher defined for them the period of the oscillations of the motion of a card to be the total time for one cycle. The students measured this time and then several asserted that it was the same as the wave period. Knowing the length of the waves and the number of waves per second, the next step can easily be to find the wave speed.

  15. The anxiety-like phenotype of 5-HT receptor null mice is associated with genetic background-specific perturbations in the prefrontal cortex GABA-glutamate system.

    PubMed

    Bruening, S; Oh, E; Hetzenauer, A; Escobar-Alvarez, S; Westphalen, R I; Hemmings, H C; Singewald, N; Shippenberg, T; Toth, M

    2006-11-01

    A deficit in the serotonin 5-HT(1A) receptor has been found in panic and post-traumatic stress disorders, and genetic inactivation of the receptor results in an anxiety-like phenotype in mice on both the C57Bl6 and Swiss-Webster genetic backgrounds. Anxiety is associated with increased neuronal activity in the prefrontal cortex and here we describe changes in glutamate and GABA uptake of C57Bl6 receptor null mice. Although these alterations were not present in Swiss-Webster null mice, we have previously reported reductions in GABA(A) receptor expression in these but not in C57Bl6 null mice. This demonstrates that inactivation of the 5-HT(1A) receptor elicits different and genetic background-dependent perturbations in the prefrontal cortex GABA/glutamate system. These perturbations can result in a change in the balance between excitation and inhibition, and indeed both C57Bl6 and Swiss-Webster null mice show signs of increased neuronal excitability. Because neuronal activity in the prefrontal cortex controls the extent of response to anxiogenic stimuli, the genetic background-specific perturbations in glutamate and GABA neurotransmission in C57Bl6 and Swiss-Webster 5-HT(1A) receptor null mice may contribute to their shared anxiety phenotype. Our study shows that multiple strains of genetically altered mice could help us to understand the common and individual features of anxiety.

  16. VLBI2010 Demonstrator Project

    NASA Astrophysics Data System (ADS)

    Niell, A.

    2008-12-01

    . Observations demonstrating the full four-band configuration are planned for October. In this talk the results of these tests, the improvements that are anticipated for the operational VLBI2010 network, and the status of other developments in the next generation of geodetic VLBI systems will be presented. * Bruce Whittier, Mike Titus, Jason SooHoo, Dan Smythe, Alan Rogers, Jay Redmond, Mike Poirier, Chuck Kodak, Alan Hinton, Ed Himwich, Skip Gordon, Mark Evangelista, Irv Diegel, Brian Corey, Tom Clark, Chris Beaudoin (in reverse alphabetical order)

  17. Demonstration of new PCSD capabilities

    NASA Technical Reports Server (NTRS)

    Gough, M.

    1986-01-01

    The new, more flexible and more friendly graphics capabilities to be available in later releases of the Pilot Climate Data System were demonstrated. The LIMS-LAMAT data set was chosen to illustrate these new capabilities. Pseudocolor and animation were used to represent the third and fourth dimensions, expanding the analytical capabilities available through the traditional two-dimensional x-y plot. In the new version, variables for the axes are chosen by scrolling through viable selections. This scrolling feature is a function of the new user interface customization. The new graphics are extremely user friendly and should free the scientist to look at data and converse with it, without doing any programming. The system is designed to rapidly plot any variable versus any other variable and animate by any variable. Any one plot in itself is not extraordinary; however, the fact that a user can generate the plots instead of a programmer distinguishes the graphics capabilities of the PCDS from other software packages. In addition, with the new CDF design, the system will become more generic, and the new graphics will become much more rigorous in the area of correlative studies.

  18. Apollo 14 composite casting demonstration

    NASA Technical Reports Server (NTRS)

    1971-01-01

    This program assisted in the design and implementation of the composite casting demonstration for the Apollo 14 mission. Both flight and control samples were evaluated. Some conclusions resulting from a comparison of the flight and control samples were: (1) Solidification in neither the flight nor control samples was truly directional. (2) Apparent intermittent contact of the melt with the container in the flight samples led to unusual nucleation and growth structures. (3) There was greater uniformity, on a macro scale, of both pores and structural features in the flight sample; presumably the result of the reduced gravity conditions. (4) It seems quite feasible to produce enhanced dispersions of gases and dense phases in a melt which is solidified in reduced gravity. (5) A two-stage heating/cooling cycle may help directional solidification. (6) Sample materials should be selected from materials in which the dispersant fully wets the matrix material. (7) Experiments should be conducted in two modes: (1) where the melt is in good thermal contact with the container, and (2) where the melt is in a free-float condition.

  19. A multidimensional representation model of geographic features

    USGS Publications Warehouse

    Usery, E. Lynn; Timson, George; Coletti, Mark

    2016-01-28

    A multidimensional model of geographic features has been developed and implemented with data from The National Map of the U.S. Geological Survey. The model, programmed in C++ and implemented as a feature library, was tested with data from the National Hydrography Dataset demonstrating the capability to handle changes in feature attributes, such as increases in chlorine concentration in a stream, and feature geometry, such as the changing shoreline of barrier islands over time. Data can be entered directly, from a comma separated file, or features with attributes and relationships can be automatically populated in the model from data in the Spatial Data Transfer Standard format.

  20. A multidimensional representation model of geographic features

    USGS Publications Warehouse

    Usery, E. Lynn; Timson, George; Coletti, Mark

    2016-01-01

    A multidimensional model of geographic features has been developed and implemented with data from The National Map of the U.S. Geological Survey. The model, programmed in C++ and implemented as a feature library, was tested with data from the National Hydrography Dataset demonstrating the capability to handle changes in feature attributes, such as increases in chlorine concentration in a stream, and feature geometry, such as the changing shoreline of barrier islands over time. Data can be entered directly, from a comma separated file, or features with attributes and relationships can be automatically populated in the model from data in the Spatial Data Transfer Standard format.

  1. Favorite Demonstrations: Gaseous Diffusion: A Demonstration of Graham's Law.

    ERIC Educational Resources Information Center

    Kauffman, George B.; Ebner, Ronald D.

    1985-01-01

    Describes a demonstration in which gaseous ammonia and hydrochloric acid are used to illustrate rates of diffusion (Graham's Law). Simple equipment needed for the demonstration include a long tube, rubber stoppes, and cotton. Two related demonstrations are also explained. (DH)

  2. The MICE luminosity monitor

    NASA Astrophysics Data System (ADS)

    Dobbs, A.; Forrest, D.; Soler, F. J. P.

    2013-02-01

    The MICE experiment will provide the first measurement of ionisation cooling, a technique suitable for reducing the transverse emittance of a tertiary muon beam in a future neutrino factory accelerator facility. MICE is presently in the final stages of commissioning its beam line. The MICE luminosity monitor has proved an invaluable tool throughout this process, providing independent measurements of particle rate from the MICE target, normalisation for beam line detectors and verification of simulation codes.

  3. Urinary Bladder Dysfunction in Transgenic Sickle Cell Disease Mice

    PubMed Central

    Claudino, Mário Angelo; Leiria, Luiz Osório Silveira; da Silva, Fábio Henrique; Alexandre, Eduardo Costa; Renno, Andre; Mónica, Fabiola Zakia; de Nucci, Gilberto; Fertrin, Kleber Yotsumoto; Antunes, Edson; Costa, Fernando Ferreira; Franco-Penteado, Carla Fernanda

    2015-01-01

    Background Urological complications associated with sickle cell disease (SCD), include nocturia, enuresis, urinary infections and urinary incontinence. However, scientific evidence to ascertain the underlying cause of the lower urinary tract symptoms in SCD is lacking. Objective Thus, the aim of this study was to evaluate urinary function, in vivo and ex vivo, in the Berkeley SCD murine model (SS). Methods Urine output was measured in metabolic cage for both wild type and SS mice (25-30 g). Bladder strips and urethra rings were dissected free and mounted in organ baths. In isolated detrusor smooth muscle (DSM), relaxant response to mirabegron and isoproterenol (1nM-10μM) and contractile response to (carbachol (CCh; 1 nM-100μM), KCl (1 mM-300mM), CaCl2 (1μM-100mM), α,β-methylene ATP (1, 3 and 10 μM) and electrical field stimulation (EFS; 1-32 Hz) were measured. Phenylephrine (Phe; 10nM-100μM) was used to evaluate the contraction mechanism in the urethra rings. Cystometry and histomorphometry were also performed in the urinary bladder. Results SS mice present a reduced urine output and incapacity to produce typical bladder contractions and bladder emptying (ex vivo), compared to control animals. In DSM, relaxation in response to a selective β3-adrenergic agonist (mirabegron) and to a non-selective β-adrenergic (isoproterenol) agonist were lower in SS mice. Additionally, carbachol, α, β-methylene ATP, KCl, extracellular Ca2+ and electrical-field stimulation promoted smaller bladder contractions in SS group. Urethra contraction induced by phenylephrine was markedly reduced in SS mice. Histological analyses of SS mice bladder revealed severe structural abnormalities, such as reductions in detrusor thickness and bladder volume, and cell infiltration. Conclusions Taken together, our data demonstrate, for the first time, that SS mice display features of urinary bladder dysfunction, leading to impairment in urinary continence, which may have an important role in

  4. Feature Clustering for Accelerating Parallel Coordinate Descent

    SciTech Connect

    Scherrer, Chad; Tewari, Ambuj; Halappanavar, Mahantesh; Haglin, David J.

    2012-12-06

    We demonstrate an approach for accelerating calculation of the regularization path for L1 sparse logistic regression problems. We show the benefit of feature clustering as a preconditioning step for parallel block-greedy coordinate descent algorithms.

  5. Biomarker Identification by Feature Wrappers

    PubMed Central

    Xiong, Momiao; Fang, Xiangzhong; Zhao, Jinying

    2001-01-01

    Gene expression studies bridge the gap between DNA information and trait information by dissecting biochemical pathways into intermediate components between genotype and phenotype. These studies open new avenues for identifying complex disease genes and biomarkers for disease diagnosis and for assessing drug efficacy and toxicity. However, the majority of analytical methods applied to gene expression data are not efficient for biomarker identification and disease diagnosis. In this paper, we propose a general framework to incorporate feature (gene) selection into pattern recognition in the process to identify biomarkers. Using this framework, we develop three feature wrappers that search through the space of feature subsets using the classification error as measure of goodness for a particular feature subset being “wrapped around”: linear discriminant analysis, logistic regression, and support vector machines. To effectively carry out this computationally intensive search process, we employ sequential forward search and sequential forward floating search algorithms. To evaluate the performance of feature selection for biomarker identification we have applied the proposed methods to three data sets. The preliminary results demonstrate that very high classification accuracy can be attained by identified composite classifiers with several biomarkers. PMID:11691853

  6. Stress inoculation modeled in mice

    PubMed Central

    Brockhurst, J; Cheleuitte-Nieves, C; Buckmaster, C L; Schatzberg, A F; Lyons, D M

    2015-01-01

    Stress inoculation entails intermittent exposure to mildly stressful situations that present opportunities to learn, practice and improve coping in the context of exposure psychotherapies and resiliency training. Here we investigate behavioral and hormonal aspects of stress inoculation modeled in mice. Mice randomized to stress inoculation or a control treatment condition were assessed for corticosterone stress hormone responses and behavior during open-field, object-exploration and tail-suspension tests. Stress inoculation training sessions that acutely increased plasma levels of corticosterone diminished subsequent immobility as a measure of behavioral despair on tail-suspension tests. Stress inoculation also decreased subsequent freezing in the open field despite comparable levels of thigmotaxis in mice from both treatment conditions. Stress inoculation subsequently decreased novel-object exploration latencies and reduced corticosterone responses to repeated restraint. These results demonstrate that stress inoculation acutely stimulates glucocorticoid signaling and then enhances subsequent indications of active coping behavior in mice. Unlike mouse models that screen for the absence of vulnerability to stress or presence of traits that occur in resilient individuals, stress inoculation training reflects an experience-dependent learning-like process that resembles interventions designed to build resilience in humans. Mouse models of stress inoculation may provide novel insights for new preventive strategies or therapeutic treatments of human psychiatric disorders that are triggered and exacerbated by stressful life events. PMID:25826112

  7. Simple Buoyancy Demonstrations Using Saltwater.

    ERIC Educational Resources Information Center

    Cosby, Ronald M.; Petry, Douglas E.

    1989-01-01

    Discusses the use of saline solutions for demonstrations of buoyancy showing oscillations of the Cartesian diver. Describes the physical principles, preparation, and instructional uses for the demonstration. (YP)

  8. MICE: a mouse imaging collaboration environment

    NASA Astrophysics Data System (ADS)

    Szymanski, Jacek; Flask, Chris; Wilson, David; Johnson, David; Muzic, Raymond F., Jr.; Zhang, Guo-Qiang

    2006-03-01

    project leader manage data access through a web-interface represent Phase I implementation. In Phase II, features for uploading image analysis scripts and results back to the MICE server will be implemented, as well as mechanisms facilitating asynchronous and synchronous discussion, annotation, and analysis. Most of MICE features are being implemented in the Plone 5 object-oriented database environment which greatly shortens developmental time and effort by the reuse of a variety of Plone's open-source modules for Content Management Systems. 7, 8 The open-source modules are well suited as an implementation basis of MICE and provide data integration as a built-in primitive.

  9. Light/dark transition test for mice.

    PubMed

    Takao, Keizo; Miyakawa, Tsuyoshi

    2006-12-01

    Although all of the mouse genome sequences have been determined, we do not yet know the functions of most of these genes. Gene-targeting techniques, however, can be used to delete or manipulate a specific gene in mice. The influence of a given gene on a specific behavior can then be determined by conducting behavioral analyses of the mutant mice. As a test for behavioral phenotyping of mutant mice, the light/dark transition test is one of the most widely used tests to measure anxiety-like behavior in mice. The test is based on the natural aversion of mice to brightly illuminated areas and on their spontaneous exploratory behavior in novel environments. The test is sensitive to anxiolytic drug treatment. The apparatus consists of a dark chamber and a brightly illuminated chamber. Mice are allowed to move freely between the two chambers. The number of entries into the bright chamber and the duration of time spent there are indices of bright-space anxiety in mice. To obtain phenotyping results of a strain of mutant mice that can be readily reproduced and compared with those of other mutants, the behavioral test methods should be as identical as possible between laboratories. The procedural differences that exist between laboratories, however, make it difficult to replicate or compare the results among laboratories. Here, we present our protocol for the light/dark transition test as a movie so that the details of the protocol can be demonstrated. In our laboratory, we have assessed more than 60 strains of mutant mice using the protocol shown in the movie. Those data will be disclosed as a part of a public database that we are now constructing. Visualization of the protocol will facilitate understanding of the details of the entire experimental procedure, allowing for standardization of the protocols used across laboratories and comparisons of the behavioral phenotypes of various strains of mutant mice assessed using this test.

  10. Impact of PPAR-α induction on glucose homoeostasis in alcohol-fed mice.

    PubMed

    Lebrun, Valérie; Molendi-Coste, Olivier; Lanthier, Nicolas; Sempoux, Christine; Cani, Patrice D; van Rooijen, Nico; Stärkel, Peter; Horsmans, Yves; Leclercq, Isabelle A

    2013-12-01

    Alcohol consumption is a major cause of liver disease. It also associates with increased cardiovascular risk and Type 2 diabetes. ALD (alcoholic liver disease) and NAFLD (non-alcoholic fatty liver disease) share pathological features, pathogenic mechanisms and pattern of disease progression. In NAFLD, steatosis, lipotoxicity and liver inflammation participate to hepatic insulin resistance. The aim of the present study was to verify the effect of alcohol on hepatic insulin sensitivity and to evaluate the role of alcohol-induced steatosis and inflammation on glucose homoeostasis. C57BL/6J mice were fed for 20 days a modified Lieber-DeCarli diet in which the alcohol concentration was gradually increased up to 35% of daily caloric intake. OH (alcohol liquid diet)-fed mice had liver steatosis and inflammatory infiltration. In addition, these mice developed insulin resistance in the liver, but not in muscles, as demonstrated by euglycaemic-hyperinsulinaemic clamp and analysis of the insulin signalling cascade. Treatment with the PPAR-α (peroxisome-proliferator-activated receptor-α) agonist Wy14,643 protected against OH-induced steatosis and KC (Kupffer cell) activation and almost abolished OH-induced insulin resistance. As KC activation may modulate insulin sensitivity, we repeated the clamp studies in mice depleted in KC to decipher the role of macrophages. Depletion of KC using liposomes-encapsuled clodronate in OH-fed mice failed both to improve hepatic steatosis and to restore insulin sensitivity as assessed by clamp. Our study shows that chronic alcohol consumption induces steatosis, KC activation and hepatic insulin resistance in mice. PPAR-α agonist treatment that prevents steatosis and dampens hepatic inflammation also prevents alcohol-induced hepatic insulin resistance. However, KC depletion has little impact on OH-induced metabolic disturbances.

  11. Protective effect of Acanthopanax gracilistylus-extracted Acankoreanogenin A on mice with fulminant hepatitis.

    PubMed

    Zhang, Bao-Xin; Li, Ning; Zhang, Zu-Ping; Liu, Hong-Bo; Zhou, Rong-Rong; Zhong, Bai-Yun; Zou, Ming-Xiang; Dai, Xia-Hong; Xiao, Mei-Fang; Liu, Xiang-Qian; Fan, Xue-Gong

    2011-08-01

    The release of pro-inflammatory cytokines in both acute (IL-1β and TNF-α) and chronic [high mobility group box 1 protein (HMGB1)] phases, is thought to play important roles in the development of fulminant hepatitis (FH). Triterpenoid Acankoreanogenin A (AA) which is extracted from the leaves of the Acanthopanax gracilistylus W.W. Smith (AGS) has shown its inhibiting effect on TNF-α, IL-1β and HMGB1 release in vitro in our preliminary experiments. In present study, we investigated the effect of AA on mice with fulminant hepatitis in vivo. Fulminant hepatitis mice model was established by intraperitoneally injecting galactosamine (GalN) and lipopolysaccharide (LPS). The levels of serum of TNF-α, IL-1β, ALT, AST and HMGB1 from AA-treated mice were measured at different time points. Our results demonstrated that pre-treatment of mice with AA markedly reduced the serum levels of TNF-α, IL-1β, HMGB1, ALT and AST with the improvement in histological features. And the survival rate from AA-treated fulminant hepatitis mice was increased. Furthermore, delayed administration of AA after peak occurrence of the early pro-inflammatory cytokines still endowed significant protection against GalN/LPS-induced lethality. The post-treatment of AA could significantly attenuate the release of HMGB1, but not the TNF-α and IL-1β. These results indicate that AA inhibits the systemic release of pro-inflammatory cytokine HMGB1, and dose-dependently rescue the mice from lethal GalN/LPS-induced fulminant hepatitis, which suggests this component as a candidate therapy for fulminant hepatitis. PMID:21356341

  12. Lupus-prone mice as models to study xenobiotic-induced acceleration of systemic autoimmunity.

    PubMed Central

    Pollard, K M; Pearson, D L; Hultman, P; Hildebrandt, B; Kono, D H

    1999-01-01

    The linkage between xenobiotic exposures and autoimmune diseases remains to be clearly defined. However, recent studies have raised the possibility that both genetic and environmental factors act synergistically at several stages or checkpoints to influence disease pathogenesis in susceptible populations. These observations predict that individuals susceptible to spontaneous autoimmunity should be more susceptible following xenobiotic exposure by virtue of the presence of predisposing background genes. To test this possibility, mouse strains with differing genetic susceptibility to murine lupus were examined for acceleration of autoimmune features characteristic of spontaneous systemic autoimmune disease following exposure to the immunostimulatory metals nickel and mercury. Although NiCl(2) exposure did not exacerbate autoimmunity, HgCl(2) significantly accelerated systemic disease in a strain-dependent manner. Mercury-exposed (NZB X NZW)F1 mice had accelerated lymphoid hyperplasia, hypergammaglobulinemia, autoantibodies, and immune complex deposits. Mercury also exacerbated immunopathologic manifestations in MRL+/+ and MR -lpr mice. However, there was less disease acceleration in lpr mice compared with MRL+/+ mice, likely due to the fact that environmental factors are less critical for disease induction when there is strong genetic susceptibility. Non-major histocompatibility complex genes also contributed to mercury-exacerbated disease, as the nonautoimmune AKR mice, which are H-2 identical with the MRL, showed less immunopathology than either the MRL/lpr or MRL+/+ strains. This study demonstrates that genetic susceptibility to spontaneous systemic autoimmunity can be a predisposing factor for HgCl(2)-induced exacerbation of autoimmunity. Such genetic predisposition may have to be considered when assessing the immunotoxicity of xenobiotics. Additional comparative studies using autoimmune-prone and nonautoimmune mice strains with different genetic backgrounds will

  13. A single dose of hypnotic corrects sleep and EEG abnormalities in symptomatic Huntington's disease mice.

    PubMed

    Kantor, Sandor; Varga, Janos; Morton, A Jennifer

    2016-06-01

    Sleep and electroencephalogram abnormalities are prominent early features of Huntington's disease (HD) that typically appear before the onset of characteristic motor symptoms. The changes in sleep and electroencephalogram seen in HD patients are largely recapitulated in mouse models of HD such as transgenic R6/2 lines. To test whether or not drugs with hypnotic properties can correct the sleep and electroencephalogram abnormalities seen in HD mice, we treated male wild-type (WT; N = 7) and R6/2 mice (N = 9) acutely with intraperitoneal injections of vehicle, zolpidem (5, 10 or 20 mg/kg) or amitriptyline (5, 10 or 20 mg/kg), and then monitored their sleep-wake behavior. In R6/2 mice, both zolpidem and amitriptyline suppressed the abnormally high REM sleep amount and electroencephalographic gamma (30-46 Hz) oscillations in a dose-dependent manner. Amitriptyline's effect on sleep was similar in both genotypes, whereas zolpidem showed significant genotype differences. Zolpidem exerted a strong hypnotic effect in WT mice by increasing electroencephalographic delta power, doubling the mean bout duration and the total amount of non-rapid eye movement sleep. However, no such effect was seen in R6/2 mice. Our study demonstrates that the pathophysiological changes seen in sleep and electroencephalogram are not 'hard-wired' in HD brain and can be reversed even at late stages of the disease. The diminished hypnotic effect of zolpidem suggests that the GABAergic control of sleep-wake states is impaired in HD mice. A better understanding of the neurochemical basis underlying these abnormalities should lead to more effective and rational therapies for HD. PMID:26805423

  14. Molecular, Physiological, and Motor Performance Defects in DMSXL Mice Carrying >1,000 CTG Repeats from the Human DM1 Locus

    PubMed Central

    Huguet, Aline; Medja, Fadia; Nicole, Annie; Vignaud, Alban; Guiraud-Dogan, Céline; Ferry, Arnaud; Decostre, Valérie; Hogrel, Jean-Yves; Metzger, Friedrich; Hoeflich, Andreas; Baraibar, Martin; Gomes-Pereira, Mário; Puymirat, Jack; Bassez, Guillaume; Furling, Denis; Munnich, Arnold; Gourdon, Geneviève

    2012-01-01

    Myotonic dystrophy type 1 (DM1) is caused by an unstable CTG repeat expansion in the 3′UTR of the DM protein kinase (DMPK) gene. DMPK transcripts carrying CUG expansions form nuclear foci and affect splicing regulation of various RNA transcripts. Furthermore, bidirectional transcription over the DMPK gene and non-conventional RNA translation of repeated transcripts have been described in DM1. It is clear now that this disease may involve multiple pathogenic pathways including changes in gene expression, RNA stability and splicing regulation, protein translation, and micro–RNA metabolism. We previously generated transgenic mice with 45-kb of the DM1 locus and >300 CTG repeats (DM300 mice). After successive breeding and a high level of CTG repeat instability, we obtained transgenic mice carrying >1,000 CTG (DMSXL mice). Here we described for the first time the expression pattern of the DMPK sense transcripts in DMSXL and human tissues. Interestingly, we also demonstrate that DMPK antisense transcripts are expressed in various DMSXL and human tissues, and that both sense and antisense transcripts accumulate in independent nuclear foci that do not co-localize together. Molecular features of DM1-associated RNA toxicity in DMSXL mice (such as foci accumulation and mild missplicing), were associated with high mortality, growth retardation, and muscle defects (abnormal histopathology, reduced muscle strength, and lower motor performances). We have found that lower levels of IGFBP-3 may contribute to DMSXL growth retardation, while increased proteasome activity may affect muscle function. These data demonstrate that the human DM1 locus carrying very large expansions induced a variety of molecular and physiological defects in transgenic mice, reflecting DM1 to a certain extent. As a result, DMSXL mice provide an animal tool to decipher various aspects of the disease mechanisms. In addition, these mice can be used to test the preclinical impact of systemic therapeutic

  15. The effects of hypermuscularity on shoulder morphology in myostatin-deficient mice

    PubMed Central

    Green, David J; Hamrick, Mark W; Richmond, Brian G

    2011-01-01

    Mechanical loads, particularly those generated by skeletal muscle, play a significant role in determining long-bone shape and strength, but it is less clear how these loads influence the morphology of flat bones like the scapula. While scapular morphology has been shown to vary with locomotor mode in mammals, this study seeks to better understand whether genetically modified muscle size can influence scapular shape in the absence of significant locomotor differences. The soft- and hard-tissue morphological characteristics were examined in 11 hypermuscular, mutant (myostatin-deficient), 20 heterozygote, and 15 wild-type mouse shoulders. Body mass did not significantly differ among the genotype groups, but homozygous mutant and heterozygote mice had significantly larger shoulder muscles than wild-type mice. Mutant mice also differed significantly from the wild-type controls in several aspects of scapular size and shape, including glenohumeral joint orientation, total scapular length, superior border length, and supraspinous and infraspinous fossa length. Conversely, several traits describing superoinferior scapular breadth measures (e.g. total breadth and dorsal scapular fossa breadth) did not significantly differ between mutant and wild-type mice. Since the intrinsic musculature of the scapula is oriented in a mediolateral fashion, it follows that mediolaterally configured hard-tissue features like scapular length were most distinct among genotype groups. As had been noted previously with long bones, this study demonstrates that genetically enhanced muscle size has marked effects on the morphological characteristics of the shoulder. PMID:21332716

  16. Estradiol-Treated Female Mice as Surrogate Hosts for Neisseria gonorrhoeae Genital Tract Infections.

    PubMed

    Jerse, Ann E; Wu, Hong; Packiam, Mathanraj; Vonck, Rachel A; Begum, Afrin A; Garvin, Lotisha E

    2011-01-01

    Historically, animal modeling of gonorrhea has been hampered by the exclusive adaptation of Neisseria gonorrhoeae to humans. Genital tract infection can be established in female mice that are treated with 17β-estradiol, however, and many features of experimental murine infection mimic human infection. Here we review the colonization kinetics and host response to experimental murine gonococcal infection, including mouse strain differences and evidence that IL-17 responses, toll-like receptor 4, and T regulatory cells play a role in infection. We also discuss the strengths and limitations of the mouse system and the potential of transgenic mice to circumvent host restrictions. Additionally, we review studies with genetically defined mutants that demonstrated a role for sialyltransferase and the MtrC-MtrD-MtrE active efflux pump in evading innate defenses in vivo, but not for factors hypothesized to protect against the phagocytic respiratory burst and H(2)O(2)-producing lactobacilli. Studies using estradiol-treated mice have also revealed the existence of non-host-restricted iron sources in the female genital tract and the influence of hormonal factors on colonization kinetics and selection for opacity (Opa) protein expression. Recent work by others with estradiol-treated mice that are transgenic for human carcinoembryonic adhesion molecules (CEACAMs) supports a role for Opa proteins in enhancing cellular attachment and thus reduced shedding of N. gonorrhoeae. Finally we discuss the use of the mouse model in product testing and a recently developed gonorrhea chlamydia coinfection model.

  17. Behavioral and Neural Correlates of Acute and Scheduled Hunger in C57BL/6 Mice

    PubMed Central

    Gunapala, Keith M.; Parfyonov, Maksim; Chang, Chris H.; Mistlberger, Ralph E.; Steele, Andrew D.

    2014-01-01

    In rodents, daily feeding schedules induce food anticipatory activity (FAA) rhythms with formal properties suggesting mediation by food-entrained circadian oscillators (FEOs). The search for the neuronal substrate of FEOs responsible for FAA is an active area of research, but studies spanning several decades have yet to identify unequivocally a brain region required for FAA. Variability of results across studies leads to questions about underlying biology versus methodology. Here we describe in C57BL/6 male mice the effects of varying the ‘dose’ of caloric restriction (0%, 60%, 80%, 110%) on the expression of FAA as measured by a video-based analysis system, and on the induction of c-Fos in brain regions that have been implicated in FAA. We determined that more severe caloric restriction (60%) leads to a faster onset of FAA with increased magnitude. Using the 60% caloric restriction, we found little evidence for unique signatures of neuronal activation in the brains of mice anticipating a daily mealtime compared to mice that were fasted acutely or fed ad-libitum–even in regions such as the dorsomedial and ventrolateral hypothalamus, nucleus accumbens, and cerebellum that have previously been implicated in FAA. These results underscore the importance of feeding schedule parameters in determining quantitative features of FAA in mice, and demonstrate dissociations between behavioral FAA and neural activity in brain areas thought to harbor FEOs or participate in their entrainment or output. PMID:24806659

  18. Unexpected improvements of spatial learning and memory abilities in chronic rotenone intoxicated mice.

    PubMed

    Jia, Fengju; Song, Ning; Zhao, Chenyang; Xie, Junxia; Jiang, Hong

    2014-01-01

    The liposoluble insecticide rotenone is commonly used as a mitochondrial complex I inhibitor to replicate Parkinson's disease (PD) pathological features. However, there was no assessment of the spatial learning and memory abilities in chronic rotenone-induced PD models. In the present study, by rotarod test and Thioflavine T staining, we first noted the impairment of motor coordination in rotenone-treated group for 3 months, as well as alpha-synuclein inclusions in the nigral dopaminergic neurons in C57BL/6 mice with intragastrical delivery of rotenone (5 mg/Kg) for 3 months rather than 1 month. We then evaluated spatial learning and memory abilities by Morris water maze task in this model. The results showed escape latency reduced in rotenone-intoxicated mice for 3 months, indicating an improvement of learning ability. However, it was delayed slightly but not significantly in rotenone-intoxicated mice for 1 month. Similarly, we demonstrated that spatial memory ability was enhanced in 3-month-treatment group, but impaired in 1-month-treatment group. There were no proliferating cell nuclear antigen and doublecortin positive cells in the hippocampus by double immunofluorescent staining, indicating the absence of hippocampal neurogenesis in rotenone-intoxicated mice. These results suggest that spatial learning and memory abilities are disturbed in chronic rotenone-intoxicated PD model.

  19. Toll-like receptor-deficient mice reveal how innate immune signaling influences Salmonella virulence strategies.

    PubMed

    Sivick, Kelsey E; Arpaia, Nicholas; Reiner, Gabrielle L; Lee, Bettina L; Russell, Bethany R; Barton, Gregory M

    2014-02-12

    Pathogens utilize features of the host response as cues to regulate virulence gene expression. Salmonella enterica serovar Typhimurium (ST) sense Toll-like receptor (TLR)-dependent signals to induce Salmonella Pathogenicity Island 2 (SPI2), a locus required for intracellular replication. To examine pathogenicity in the absence of such cues, we evaluated ST virulence in mice lacking all TLR function (Tlr2(-/-)xTlr4(-/-)xUnc93b1(3d/3d)). When delivered systemically to TLR-deficient mice, ST do not require SPI2 and maintain virulence by replicating extracellularly. In contrast, SPI2 mutant ST are highly attenuated after oral infection of the same mice, revealing a role for SPI2 in the earliest stages of infection, even when intracellular replication is not required. This early requirement for SPI2 is abolished in MyD88(-/-)xTRIF(-/-) mice lacking both TLR- and other MyD88-dependent signaling pathways, a potential consequence of compromised intestinal permeability. These results demonstrate how pathogens use plasticity in virulence strategies to respond to different host immune environments.

  20. Functional consequences of EpCam mutation in mice and men.

    PubMed

    Mueller, James L; McGeough, Matthew D; Peña, Carla A; Sivagnanam, Mamata

    2014-02-15

    Congenital tufting enteropathy (CTE) is a severe diarrheal disease of infancy characterized by villous changes and epithelial tufts. We previously identified mutations in epithelial cell adhesion molecule (EpCAM) as the cause of CTE. We developed an in vivo mouse model of CTE based on EpCAM mutations found in patients with the aim to further elucidate the in vivo role of EpCAM and allow for a direct comparison to human CTE. Using Cre-LoxP recombination technology, we generated a construct lacking exon 4 in Epcam. Epcam(Δ4/Δ4) mice and CTE patient intestinal tissue integrity was analyzed by histology using both light immunohistochemistry and electron microscopy. Epcam(Δ4/Δ4) mice demonstrate neonatal lethality and growth retardation with pathological features, including epithelial tufts, enterocyte crowding, altered desmosomes, and intercellular gaps, similar to human CTE patients. Mutant EpCAM protein is present at low levels and is mislocalized in the intestine of Epcam(Δ4/Δ4) mice and CTE patients. Deletion of exon 4 was found to decrease expression of both EpCAM and claudin-7 causing a loss of colocalization, functionally disrupting the EpCAM/claudin-7 complex, a finding for the first time confirmed in CTE patients. Furthermore, compared with unaffected mice, mutation of Epcam leads to enhanced permeability and intestinal cell migration, uncovering underlying disease mechanisms.

  1. Differential proteomic analysis of STAT6 knockout mice reveals new regulatory function in liver lipid homeostasis.

    PubMed

    Iff, Joël; Wang, Wei; Sajic, Tatjana; Oudry, Nathalie; Gueneau, Estelle; Hopfgartner, Gérard; Varesio, Emmanuel; Szanto, Ildiko

    2009-10-01

    Increased inflammatory signaling is a key feature of metabolic disorders. In this context, the role of increased pro-inflammatory signals has been extensively studied. By contrast, no efforts have been dedicated to study the contrasting scenario: the attenuation of anti-inflammatory signals and their role in metabolic homeostasis. IL-4 and IL-13 are anti-inflammatory cytokines signaling through the Signal Transducer and Activator of Transcription 6 (STAT6). Our study was aimed at evaluating the lack of STAT6 signaling on liver homeostasis. To this end we analyzed the liver proteome of wild type and STAT6 knock-out mice using 2D nanoscale LC-MS/MS with iTRAQ labeling technique. The coordinated changes in proteins identified by this quantitative proteome analysis indicated disturbed lipid homeostasis and a state of hepatocellular stress. Most significantly, the expression of the liver fatty acid binding protein (FABP1) was increased in the knock-out mice. In line with the elevated FABP1 expression we found latent liver lipid accumulation in the STAT6-deficient mice which was further aggravated when mice were challenged by a high fat diet. In conclusion, our study revealed a so far uncharacterized role for STAT6 in regulating liver lipid homeostasis and demonstrates the importance of anti-inflammatory signaling in the defense against the development of liver steatosis.

  2. Adaptive feature extraction expert

    SciTech Connect

    Yuschik, M.

    1983-01-01

    The identification of discriminatory features places an upper bound on the recognition rate of any automatic speech recognition (ASR) system. One way to structure the extraction of features is to construct an expert system which applies a set of rules to identify particular properties of the speech patterns. However, these patterns vary for an individual speaker and from speaker to speaker so that another expert is actually needed to learn the new variations. The author investigates the problem by using sets of discriminatory features that are suggested by a feature generation expert, improves the selectivity of these features with a training expert, and finally develops a minimally spanning feature set with a statistical selection expert. 12 references.

  3. Increased Incidence of Squamous Cell Carcinomas in Mastomys natalensis Papillomavirus E6 Transgenic Mice during Two-Stage Skin Carcinogenesis

    PubMed Central

    Helfrich, Iris; Chen, Min; Schmidt, Rainer; Fürstenberger, Gerhard; Kopp-Schneider, Annette; Trick, David; Gröne, Hermann-Josef; zur Hausen, Harald; Rösl, Frank

    2004-01-01

    Papillomaviruses cause certain forms of human cancers, most notably carcinomas of the uterine cervix. In contrast to the well-established involvement of papillomavirus infection in the etiology of cervical carcinomas and in carcinomas of a rare hereditary condition, epidermodysplasia verruciformis, a causative role for cutaneous human papillomavirus types in the development of nonmelanoma skin cancer has not been proven. In order to better understand the functions of individual genes of cutaneous papillomavirus types, we generated transgenic mice carrying oncogene E6 of the Mastomys natalensis papillomavirus (MnPV), which causes keratoacanthomas of the skin in its natural host. In the present study, we demonstrate that under conditions of experimental two-stage skin carcinogenesis, fast-paced squamous cell carcinomas develop in nearly 100% of MnPV E6 transgenic mice in comparison to 10% in their nontransgenic littermates (log rank test; P < 0.0001). Therefore, we conclude that the MnPV E6 transgene favors the malignant progression of chemically induced tumors. Whereas an activating H-ras mutation is a consistent feature in benign and malignant tumors in wild-type mice, the majority of papillomas and keratoacanthomas and all squamous cell carcinomas obtained in MnPV E6 transgenic mice contain nonmutated ras alleles. These results indicate that the development of squamous cell carcinomas in MnPV E6 transgenic mice does not depend on an activated H-ras oncogene. PMID:15078961

  4. Growth Hormone (GH) Hypersecretion and GH Receptor Resistance in Streptozotocin Diabetic Mice in Response to a GH Secretagogue

    PubMed Central

    Segev, Yael; Landau, Daniel; Phillip, Moshe; Flyvbjerg, Allan

    2003-01-01

    The growth hormone (GH) and insulin-like growth factor I (IGF-I) axis were studied in streptozotocin (STZ) diabetic and nondiabetic female mice following intravenous (IV) injection of the GH secretagogue (GHS) ipamorelin or saline. On day 14, blood samples were obtained before and 10 minutes after the injection. Livers were removed and frozen for determination of the mRNA expressions of the GH receptor, GH-binding protein, and IGF-I, and hepatic IGF-I peptide. Serum samples were analyzed for GH and IGF-I. Following ipamorelin injection, the GH levels were found to be 150 ± 35 μg/L and 62 ± 11 μg/L in the diabetic compared to the nondiabetic mice (P < .05). Serum IGF-I levels were lower in diabetic than in nondiabetic animals, and rose after stimulation only in the nondiabetic animals. Furthermore, hepatic GH resistance and IGF-I mRNA levels and IGF-I peptide were increased in nondiabetic animals in response to GH stimulation, whereas the low levels per se of all these parameters in diabetic mice were unaffected. The study shows that STZ diabetic mice demonstrate a substantial part of the clinical features of type 1 diabetes in humans, including GH hypersecretion and GH resistance. Accordingly, it is proposed that STZ diabetic mice may be a better model of the perturbations of the GH/IGF-I axis in diabetes than STZ diabetic rats. PMID:14630569

  5. Quantification of alcohol drinking patterns in mice.

    PubMed

    Eisenhardt, Manuela; Leixner, Sarah; Spanagel, Rainer; Bilbao, Ainhoa

    2015-11-01

    The use of mice in alcohol research provides an excellent model system for a better understanding of the genetics and neurobiology of alcohol addiction. Almost 60 years ago, alcohol researchers began to test strains of mice for alcohol preference and intake. In particular, various voluntary alcohol drinking paradigms in the home cage were developed. In mouse models of voluntary oral alcohol consumption, animals have concurrent access to water and either one or several concentrated alcohol solutions in their home cages. Although these models have high face validity, many experimental conditions require a more precise monitoring of alcohol consumption in mice in order to capture the role of specific strains or genes, or any other manipulation on alcohol drinking behavior. Therefore, we have developed a fully automated, highly precise monitoring system for alcohol drinking in mice in the home cage. This system is now commercially available. We show that this drinkometer system allows for detecting differences in drinking behavior (i) in transgenic mice, (ii) following alcohol deprivation, and (iii) following stress applications that are usually not detected by classical home-cage drinking paradigms. In conclusion, our drinkometer system allows disturbance-free and high resolution monitoring of alcohol drinking behavior. In particular, micro-drinking and circadian drinking patterns can be monitored in genetically modified and inbred strains of mice after environmental and pharmacological manipulation, and therefore this system represents an improvement in measuring behavioral features that are of relevance for the development of alcohol use disorders.

  6. Buried Waste Integrated Demonstration lessons learned: 1993 technology demonstrations

    SciTech Connect

    Kostelnik, K.M.; Owens, K.J.

    1994-12-31

    An integrated technology demonstration was conducted by the Buried Waste Integrated Demonstration (BWID) at the Idaho National Engineering Laboratory Cold Test Pit in the summer of 1993. This program and demonstration was sponsored by the US Department of Energy Office of Technology Development. The demonstration included six technologies representing a synergistic system for the characterization and retrieval of a buried hazardous waste site. The integrated technology demonstration proved very successful and a summary of the technical accomplishments is presented. Upon completion of the integrated technology demonstration, cognizant program personnel participated in a lessons learned exercise. This exercise was conducted at the Simplot Decision Support Center at Idaho State University and lessons learned activity captured additional information relative to the integration of technologies for demonstration purposes. This information will be used by BWID to enhance program planning and strengthen future technology demonstrations.

  7. Primordial features and Planck polarization

    NASA Astrophysics Data System (ADS)

    Hazra, Dhiraj Kumar; Shafieloo, Arman; Smoot, George F.; Starobinsky, Alexei A.

    2016-09-01

    With the Planck 2015 Cosmic Microwave Background (CMB) temperature and polarization data, we search for possible features in the primordial power spectrum (PPS). We revisit the Wiggly Whipped Inflation (WWI) framework and demonstrate how generation of some particular primordial features can improve the fit to Planck data. WWI potential allows the scalar field to transit from a steeper potential to a nearly flat potential through a discontinuity either in potential or in its derivatives. WWI offers the inflaton potential parametrizations that generate a wide variety of features in the primordial power spectra incorporating most of the localized and non-local inflationary features that are obtained upon reconstruction from temperature and polarization angular power spectrum. At the same time, in a single framework it allows us to have a background parameter estimation with a nearly free-form primordial spectrum. Using Planck 2015 data, we constrain the primordial features in the context of Wiggly Whipped Inflation and present the features that are supported both by temperature and polarization. WWI model provides more than 13 improvement in χ2 fit to the data with respect to the best fit power law model considering combined temperature and polarization data from Planck and B-mode polarization data from BICEP and Planck dust map. We use 2-4 extra parameters in the WWI model compared to the featureless strict slow roll inflaton potential. We find that the differences between the temperature and polarization data in constraining background cosmological parameters such as baryon density, cold dark matter density are reduced to a good extent if we use primordial power spectra from WWI. We also discuss the extent of bispectra obtained from the best potentials in arbitrary triangular configurations using the BI-spectra and Non-Gaussianity Operator (BINGO).

  8. Social transfer of pain in mice

    PubMed Central

    Smith, Monique L.; Hostetler, Caroline M.; Heinricher, Mary M.; Ryabinin, Andrey E.

    2016-01-01

    A complex relationship exists between the psychosocial environment and the perception and experience of pain, and the mechanisms of the social communication of pain have yet to be elucidated. The present study examined the social communication of pain and demonstrates that “bystander” mice housed and tested in the same room as mice subjected to inflammatory pain or withdrawal from morphine or alcohol develop corresponding hyperalgesia. Olfactory cues mediate the transfer of hyperalgesia to the bystander mice, which can be measured using mechanical, thermal, and chemical tests. Hyperalgesia in bystanders does not co-occur with anxiety or changes in corticosterone and cannot be explained by visually dependent emotional contagion or stress-induced hyperalgesia. These experiments reveal the multifaceted relationship between the social environment and pain behavior and support the use of mice as a model system for investigating these factors. In addition, these experiments highlight the need for proper consideration of how experimental animals are housed and tested. PMID:27774512

  9. IL-4 Knock out Mice Display Anxiety-like Behavior

    PubMed Central

    Moon, Morgan L.; Joesting, Jennifer J.; Blevins, Neil A.; Lawson, Marcus A.; Gainey, Stephen J.; Towers, Albert E.; McNeil, Leslie K.; Freund, Gregory G.

    2015-01-01

    Inflammation is a recognized antecedent and coincident factor when examining the biology of anxiety. Little is known, however, about how reductions in endogenous anti-inflammatory mediators impact anxiety. Therefore, mood- cognition- and anxiety-associated/like behaviors were examined in IL-4 knock out (KO) mice and wild-type (WT) mice. In comparison to WT mice, IL-4 KO mice demonstrated decreased burrowing and increased social exploration. No differences were seen in forced swim or saccharine preference testing. IL-4 KO mice had similar performance to WT mice in the Morris water maze and during object location and novel object recognition. In the elevated zero-maze, IL-4 KO mice, in comparison to WT mice, demonstrated anxiety-like behavior. Anxiety-like behavior in IL-4 KO mice was not observed, however, during open-field testing. Taken together, these data indicate that IL-4 KO mice display state, but not trait, anxiety suggesting that reductions in endogenous anti-inflammatory bioactives can engender subtypes of anxiety. PMID:25772794

  10. IL-4 Knock Out Mice Display Anxiety-Like Behavior.

    PubMed

    Moon, Morgan L; Joesting, Jennifer J; Blevins, Neil A; Lawson, Marcus A; Gainey, Stephen J; Towers, Albert E; McNeil, Leslie K; Freund, Gregory G

    2015-07-01

    Inflammation is a recognized antecedent and coincident factor when examining the biology of anxiety. Little is known, however, about how reductions in endogenous anti-inflammatory mediators impact anxiety. Therefore, mood- cognition- and anxiety-associated/like behaviors were examined in IL-4 knock out (KO) mice and wild-type (WT) mice. In comparison to WT mice, IL-4 KO mice demonstrated decreased burrowing and increased social exploration. No differences were seen in forced swim or saccharine preference testing. IL-4 KO mice had similar performance to WT mice in the Morris water maze and during object location and novel object recognition. In the elevated zero-maze, IL-4 KO mice, in comparison to WT mice, demonstrated anxiety-like behavior. Anxiety-like behavior in IL-4 KO mice was not observed, however, during open-field testing. Taken together, these data indicate that IL-4 KO mice display state, but not trait, anxiety suggesting that reductions in endogenous anti-inflammatory bioactives can engender subtypes of anxiety.

  11. Histopathological Study of the Lungs of Mice Receiving Human Secretory IgA and Challenged with Mycobacterium tuberculosis

    PubMed Central

    ALVAREZ, Nadine; INFANTE, Juan Francisco; BORRERO, Reinier; MATA, Dulce; PAYAN, JORGE BARRIOS-; HOSSAIN, Md. Murad; MOHD NOR, Norazmi; SARMIENTO, María Elena; HERNANDEZ-PANDO, Rogelio; ACOSTA, Armando

    2014-01-01

    Background: Humoral and cellular immune responses are associated with protection against extracellular and intracellular pathogens, respectively. In the present study, we evaluated the effect of receiving human secretory immunoglobulin A (hsIgA) on the histopathology of the lungs of mice challenged with virulent Mycobacterium tuberculosis. Methods: The hsIgA was purified from human colostrum and administered to Balb/c mice by the intranasal route prior to infection with M. tuberculosis or in a pre-incubated formulation with mycobacteria, with the principal aim to study its effect on qualitative pulmonary histopathology. Results: The intranasal administration of hsIgA and the pre-incubation of mycobacteria with this preparation was associated with the presence of organised granulomas with signs of immune activation and histological features related to efficient disease control. This effect was highly evident during the late stage of infection (60 days), as demonstrated by numerous organised granulomas with numerous activated macrophages in the lungs of treated mice. Conclusion: The administration of hsIgA to mice before intratracheal infection with M. tuberculosis or the pre-incubation of the bacteria with the antibody formulation induced the formation of well-organised granulomas and inflammatory lesions in lungs compared with non-treated animals which correlates with the protective effect already demonstrated by these antibody formulations. PMID:25246833

  12. Experimental demonstration of composite adiabatic passage

    NASA Astrophysics Data System (ADS)

    Schraft, Daniel; Halfmann, Thomas; Genov, Genko T.; Vitanov, Nikolay V.

    2013-12-01

    We report an experimental demonstration of composite adiabatic passage (CAP) for robust and efficient manipulation of two-level systems. The technique represents a altered version of rapid adiabatic passage (RAP), driven by composite sequences of radiation pulses with appropriately chosen phases. We implement CAP with radio-frequency pulses to invert (i.e., to rephase) optically prepared spin coherences in a Pr3+:Y2SiO5 crystal. We perform systematic investigations of the efficiency of CAP and compare the results with conventional π pulses and RAP. The data clearly demonstrate the superior features of CAP with regard to robustness and efficiency, even under conditions of weakly fulfilled adiabaticity. The experimental demonstration of composite sequences to support adiabatic passage is of significant relevance whenever a high efficiency or robustness of coherent excitation processes need to be maintained, e.g., as required in quantum information technology.

  13. Defeating feature fatigue.

    PubMed

    Rust, Roland T; Thompson, Debora Viana; Hamilton, Rebecca W

    2006-02-01

    Consider a coffeemaker that offers 12 drink options, a car with more than 700 features on the dashboard, and a mouse pad that's also a clock, calculator, and FM radio. All are examples of "feature bloat", or "featuritis", the result of an almost irresistible temptation to load products with lots of bells and whistles. The problem is that the more features a product boasts, the harder it is to use. Manufacturers that increase a product's capability--the number of useful functions it can perform--at the expense of its usability are exposing their customers to feature fatigue. The authors have conducted three studies to gain a better understanding of how consumers weigh a product's capability relative to its usability. They found that even though consumers know that products with more features are harder to use, they initially choose high-feature models. They also pile on more features when given the chance to customize a product for their needs. Once consumers have actually worked with a product, however, usability starts to matter more to them than capability. For managers in consumer products companies, these findings present a dilemma: Should they maximize initial sales by designing high-feature models, which consumers consistently choose, or should they limit the number of features in order to enhance the lifetime value of their customers? The authors' analytical model guides companies toward a happy middle ground: maximizing the net present value of the typical customer's profit stream. The authors also advise companies to build simpler products, help consumers learn which products suit their needs, develop products that do one thing very well, and design market research in which consumers use actual products or prototypes.

  14. Time Varying Feature Data

    NASA Astrophysics Data System (ADS)

    Echterhoff, J.; Simonis, I.; Atkinson, R.

    2012-04-01

    The infrastructure to gather, store and access information about our environment is improving and growing rapidly. The increasing amount of information allows us to get a better understanding of the current state of our environment, historical processes and to simulate and predict the future state of the environment. Finer grained spatial and temporal data and more reliable communications make it easier to model dynamic states and ephemeral features. The exchange of information within and across geospatial domains is facilitated through the use of harmonized information models. The Observations & Measurements (O&M) developed through OGC and standardised by ISO is an example of such a cross-domain information model. It is used in many domains, including meteorology, hydrology as well as the emergency management. O&M enables harmonized representation of common metadata that belong to the act of determining the state of a feature property, whether by sensors, simulations or humans. In addition to the resulting feature property value, information such as the result quality but especially the time that the result applies to the feature property can be represented. Temporal metadata is critical to modelling past and future states of a feature. The features, and the semantics of each property, are defined in domain specific Application Schema using the General Feature Model (GFM) from ISO 19109 and usually encoded following ISO 19136. However, at the moment these standards provide only limited support for the representation and handling of time varying feature data. Features like rivers, wildfires or gas plumes have a defined state - for example geographic extent - at any given point in time. To keep track of changes, a more complex model for example using time-series coverages is required. Furthermore, the representation and management of feature property value changes via the service interfaces defined by OGC and ISO - namely: WFS and WCS - would be rather complex

  15. Hepatic immunophenotyping for streptozotocin-induced hyperglycemia in mice

    PubMed Central

    Lee, Young-Sun; Eun, Hyuk Soo; Kim, So Yeon; Jeong, Jong-Min; Seo, Wonhyo; Byun, Jin-Seok; Jeong, Won-Il; Yi, Hyon-Seung

    2016-01-01

    Emerging evidence revealed that diabetes induces abnormal immune responses that result in serious complications in organs. However, the effect of hyperglycemia on hepatic immunity remains obscure. We evaluated the population and function of hepatic immune cells in streptozotocin (STZ)-induced hyperglycemic mice. CC chemokine receptor 2 (CCR2)-knockout mice and mice with a depletion of regulatory T cells (DEREG) were used to investigate the migration and role of regulatory T cells (Tregs) in hyperglycemic mice. The inflammatory cytokines and hepatic transaminase levels were significantly increased in the hyperglycemic mice. The population and number of infiltrating monocytes, granulocytes, and Tregs were enhanced in the livers of the hyperglycemic mice. Hepatic monocytes other than macrophages showed the increased expression of inflammatory cytokines and chemokines in the hyperglycemic mice. The CCR2 knockout and DEREG chimeric mice exhibited increased populations of activated T cells and neutrophils compared to the WT chimeric mice, which promoted hepatic inflammation in the hyperglycemic mice. The migration of CCR2 knockout Tregs into the liver was significantly reduced compared to the WT Tregs. We demonstrated that hyperglycemia contributes to increase in infiltrating monocytes and Tregs, which are associated with hepatic immune dysfunction in mice. CCR2-mediated migration of Tregs regulates hyperglycemia-induced hepatic inflammation. PMID:27464894

  16. A Dramatic Flame Test Demonstration.

    ERIC Educational Resources Information Center

    Johnson, Kristin A.; Schreiner, Rodney

    2001-01-01

    Flame tests are used for demonstration of atomic structure. Describes a demonstration that uses spray bottles filled with methanol and a variety of salts to produce a brilliantly colored flame. (Contains 11 references.) (ASK)

  17. Revisiting the Electric Pickle Demonstration

    ERIC Educational Resources Information Center

    Journal of Chemical Education, 2005

    2005-01-01

    The electric pickle is a classic demonstration that is widely used in both high school and college settings to explain the general principles behind atomic emission. The demonstration fails to provide an interesting multi-line spectrum.

  18. Mathematical modeling of left ventricular dimensional changes in mice during aging.

    PubMed

    Yang, Tianyi; Chiao, Ying Ann; Wang, Yunji; Voorhees, Andrew; Han, Hai-Chao; Lindsey, Merry L; Jin, Yu-Fang

    2012-01-01

    Cardiac aging is characterized by diastolic dysfunction of the left ventricle (LV), which is due in part to increased LV wall stiffness. In the diastolic phase, myocytes are relaxed and extracellular matrix (ECM) is a critical determinant to the changes of LV wall stiffness. To evaluate the effects of ECM composition on cardiac aging, we developed a mathematical model to predict LV dimension and wall stiffness changes in aging mice by integrating mechanical laws and our experimental results. We measured LV dimension, wall thickness, LV mass, and collagen content for wild type (WT) C57/BL6J mice of ages ranging from 7.3 months to those of 34.0 months. The model was established using the thick wall theory and stretch-induced tissue growth to an isotropic and homogeneous elastic composite with mixed constituents. The initial conditions of the simulation were set based on the data from the young mice. Matlab simulations of this mathematical model demonstrated that the model captured the major features of LV remodeling with age and closely approximated experimental results. Specifically, the temporal progression of the LV interior and exterior dimensions demonstrated the same trend and order-of-magnitude change as our experimental results. In conclusion, we present here a validated mathematical model of cardiac aging that applies the thick-wall theory and stretch-induced tissue growth to LV remodeling with age. PMID:23281647

  19. A Cyclosporine-Sensitive Psoriasis-Like Disease Produced in Tie2 Transgenic Mice

    PubMed Central

    Voskas, Daniel; Jones, Nina; Van Slyke, Paul; Sturk, Celina; Chang, Wing; Haninec, Alex; Babichev, Yael Olya; Tran, Jennifer; Master, Zubin; Chen, Stephen; Ward, Nicole; Cruz, Maribelle; Jones, Jamie; Kerbel, Robert S.; Jothy, Serge; Dagnino, Lina; Arbiser, Jack; Klement, Giannoula; Dumont, Daniel J.

    2005-01-01

    Psoriasis is a common, persistent skin disorder characterized by recurrent erythematous lesions thought to arise as a result of inflammatory cell infiltration and activation of keratinocyte proliferation. Unscheduled angiogenic growth has also been proposed to mediate the pathogenesis of psoriasis although the cellular and molecular basis for this response remains unclear. Recently, a role for the angiopoietin signaling system in psoriasis has been suggested by studies that demonstrate an up-regulation of the tyrosine kinase receptor Tie2 (also known as Tek) as well as angiopoietin-1 and angiopoietin-2 in human psoriatic lesions. To examine temporal expression of Tie2, we have developed a binary transgenic approach whereby expression of Tie2 can be conditionally regulated by the presence of tetracycline analogs in double-transgenic mice. A psoriasis-like phenotype developed in double-transgenic animals within 5 days of birth and persisted throughout adulthood. The skin of affected mice exhibited many cardinal features of human psoriasis including epidermal hyperplasia, inflammatory cell accumulation, and altered dermal angiogenesis. These skin abnormalities resolved completely with tetracycline-mediated suppression of transgene expression, thereby illustrating a complete dependence on Tie2 signaling for disease maintenance and progression. Furthermore, the skin lesions in double-transgenic mice markedly improved after administration of the immunosuppressive anti-psoriatic agent cyclosporine, thus demonstrating the clinical significance of this new model. PMID:15743796

  20. Favorite Demonstrations for College Science

    ERIC Educational Resources Information Center

    Shmaefsky, Brian

    2004-01-01

    Peer-reviewed, classroom-tested, and tailored specifically for introductory science courses, Favorite Demonstrations is a complement to every college instructor's lesson plans. The book is an all-in-one compilation of 36 popular classroom demonstrations published since 1993 in the "Favorite Demonstration" column of NSTA's Journal of College …

  1. Fabrication, Testing and Modeling of the MICE Superconducting Spectrometer Solenoids

    SciTech Connect

    Virostek, S.P.; Green, M.A.; Trillaud, F.; Zisman, M.S.

    2010-05-16

    The Muon Ionization Cooling Experiment (MICE), an international collaboration sited at Rutherford Appleton Laboratory in the UK, will demonstrate ionization cooling in a section of realistic cooling channel using a muon beam. A five-coil superconducting spectrometer solenoid magnet will provide a 4 tesla uniform field region at each end of the cooling channel. Scintillating fiber trackers within the 400 mm diameter magnet bore tubes measure the emittance of the beam as it enters and exits the cooling channel. Each of the identical 3-meter long magnets incorporates a three-coil spectrometer magnet section and a two-coil section to match the solenoid uniform field into the other magnets of the MICE cooling channel. The cold mass, radiation shield and leads are currently kept cold by means of three two-stage cryocoolers and one single-stage cryocooler. Liquid helium within the cold mass is maintained by means of a re-condensation technique. After incorporating several design changes to improve the magnet cooling and reliability, the fabrication and acceptance testing of the spectrometer solenoids have proceeded. The key features of the spectrometer solenoid magnets, the development of a thermal model, the results of the recently completed tests, and the current status of the project are presented.

  2. Orthotopic xenografts of RCC retain histological, immunophenotypic and genetic features of tumors in patients

    PubMed Central

    Grisanzio, Chiara; Seeley, Apryle; Chang, Michelle; Collins, Michael; Di Napoli, Arianna; Cheng, Su-Chun; Percy, Andrew; Beroukhim, Rameen; Signoretti, Sabina

    2013-01-01

    Renal cell carcinoma (RCC) is an aggressive malignancy with limited responsiveness to existing treatments. In vivo models of human cancer, including RCC, are critical for developing more effective therapies. Unfortunately, current RCC models do not accurately represent relevant properties of the human disease. The goal of this study was to develop clinically relevant animal models of RCC for preclinical investigations. We transplanted intact human tumor tissue fragments orthotopically in immunodeficient mice. The xenografts were validated by comparing the morphologic, phenotypic, and genetic characteristics of the kidney tumor tissues before and after implantation. Twenty kidney tumors were transplanted into mice. Successful tumor growth was detected in 19 cases (95%). The histopathologic and immunophenotypic features of the xenografts and those of the original tumors largely overlapped in all the cases. Evaluation of genetic alterations in a subset of 10 cases demonstrated that the grafts largely retained the genetic features of the pre-implantation RCC tissues. Indeed, primary tumors and corresponding grafts displayed identical VHL mutations. Moreover, an identical pattern of DNA copy amplification or loss was observed in 6 of 10 cases (60%). In summary, orthotopic engrafting of RCC tissue fragments can be successfully used to generate animal models that closely resemble RCC in patients. These models will be invaluable for in vivo preclinical drug testing, and for deeper understanding of kidney carcinogenesis. PMID:21710693

  3. New features in MEDM.

    SciTech Connect

    Evans, K., Jr.

    1999-04-13

    MEDM, which is derived from Motif Editor and Display Manager, is the primary graphical interface to the EPICS control system. This paper describes new features that have been added to MEDM in the last two years. These features include new editing capabilities, a PV Info dialog box, a means of specifying limits and precision, a new implementation of the Cartesian Plot, new features for several objects, new capability for the Related Display, help, a user-configurable Execute Menu, reconfigured start-up options, and availability for Windows 95/98/NT. Over one hundred bugs have been fixed, and the program is quite stable and in extensive use.

  4. Normal keratinized mucosa transplants in nude mice.

    PubMed

    Holmstrup, P; Dabelsteen, E; Reibel, J; Harder, F

    1981-01-01

    Two types of normal keratinized mucosa were transplanted to subcutaneous sites of nude mice of two different strains. 24 intact specimens of clinically normal human palatal mucosa were transplanted to nude mice of the strain nu/nu NC. The transplants were recovered after 42 d with a recovery rate of 96%. Moreover, 22 intact specimens of normal rat forestomach mucosa were transplanted to nude mice of the strain nu/nu BALB/c/BOM. These transplants were recovered after 21 d with a recovery rate of 63%. The histologic features of the transplants were essentially the same as those of the original tissues. However, epithelial outgrowths from the transplants differed with respect to the pattern of keratinization. The outgrowths of human palatal mucosa transplants were essentially unkeratinized, while the outgrowths of the rat forestomach transplants showed continued keratinization.

  5. Naegleria australiensis: experimental meningoencephalitis in mice.

    PubMed

    De Jonckheere, J F; Aerts, M; Martinez, A J

    1983-01-01

    Naegleria australiensis was recently described as a new species of free-living amoeba pathogenic for mice. Infections of human brain by the free-living amoebae N. fowleri and Acanthamoeba spp. are well known. We here describe the clinicopathological features of experimental infection of the central nervous system of mice by N. australiensis. Weanling mice were inoculated intranasally and intracerebrally. The involvement of the nasal mucosa, olfactory neuroepithelium and lobes, cerebrum and cerebellum was detected in haematoxylin-eosin stained paraffin-embedded sections. Amoebic trophozoites sparsely located throughout the central nervous system were shown better by the immunoperoxidase method. Cysts were not detected. The histopathological changes differ from those produced by N. fowleri, especially in the degree of severity. They may be confused with those caused by Acanthamoeba spp. which usually produced subacute and chronic encephalitis with a prolonged clinical course. PMID:6659050

  6. Budget constrained non-monotonic feature selection.

    PubMed

    Yang, Haiqin; Xu, Zenglin; Lyu, Michael R; King, Irwin

    2015-11-01

    Feature selection is an important problem in machine learning and data mining. We consider the problem of selecting features under the budget constraint on the feature subset size. Traditional feature selection methods suffer from the "monotonic" property. That is, if a feature is selected when the number of specified features is set, it will always be chosen when the number of specified feature is larger than the previous setting. This sacrifices the effectiveness of the non-monotonic feature selection methods. Hence, in this paper, we develop an algorithm for non-monotonic feature selection that approximates the related combinatorial optimization problem by a Multiple Kernel Learning (MKL) problem. We justify the performance guarantee for the derived solution when compared to the global optimal solution for the related combinatorial optimization problem. Finally, we conduct a series of empirical evaluation on both synthetic and real-world benchmark datasets for the classification and regression tasks to demonstrate the promising performance of the proposed framework compared with the baseline feature selection approaches.

  7. Volcanic features of Io

    USGS Publications Warehouse

    Carr, M.H.; Masursky, H.; Strom, R.G.; Terrile, R.J.

    1979-01-01

    Volcanic activity is apparently higher on Io than on any other body in the Solar System. Its volcanic landforms can be compared with features on Earth to indicate the type of volcanism present on Io. ?? 1979 Nature Publishing Group.

  8. Feature Characterization Library

    2006-08-03

    FCLib is a data analysis toolkit constructed to meet the needs of data discovery in large-scale, spatio-temporal data such as finite element simulation data. FCLib is a C library toolkit of building blocks that can be assembled into complex analyses. Important features of FCLib include the following: (1) Support of feature-based analysis, (2) minimization of low-oevel processing, (3) ease of use, and (4) applicable to the wide variety of science domains.

  9. Demonstrations with a Vacuum: Old Demonstrations for New Vacuum Pumps.

    ERIC Educational Resources Information Center

    Greenslade, Thomas B., Jr.

    1989-01-01

    Explains mechanisms of 19th-century vacuum pumps. Describes demonstrations using the pump including guinea and feather tube, aurora tube, electric egg, Gassiots cascade, air mill, bell in vacuum, density and buoyancy of air, fountain in vacuum, mercury shower, palm and bladder glasses, Bacchus demonstration, pneumatic man-lifter, and Magdeburg…

  10. Gliovascular disruption and cognitive deficits in a mouse model with features of small vessel disease

    PubMed Central

    Holland, Philip R; Searcy, James L; Salvadores, Natalia; Scullion, Gillian; Chen, Guiquan; Lawson, Greig; Scott, Fiona; Bastin, Mark E; Ihara, Masafumi; Kalaria, Rajesh; Wood, Emma R; Smith, Colin; Wardlaw, Joanna M; Horsburgh, Karen

    2015-01-01

    Cerebral small vessel disease (SVD) is a major cause of age-related cognitive impairment and dementia. The pathophysiology of SVD is not well understood and is hampered by a limited range of relevant animal models. Here, we describe gliovascular alterations and cognitive deficits in a mouse model of sustained cerebral hypoperfusion with features of SVD (microinfarcts, hemorrhage, white matter disruption) induced by bilateral common carotid stenosis. Multiple features of SVD were determined on T2-weighted and diffusion-tensor magnetic resonance imaging scans and confirmed by pathologic assessment. These features, which were absent in sham controls, included multiple T2-hyperintense infarcts and T2-hypointense hemosiderin-like regions in subcortical nuclei plus increased cerebral atrophy compared with controls. Fractional anisotropy was also significantly reduced in several white matter structures including the corpus callosum. Investigation of gliovascular changes revealed a marked increase in microvessel diameter, vascular wall disruption, fibrinoid necrosis, hemorrhage, and blood–brain barrier alterations. Widespread reactive gliosis, including displacement of the astrocytic water channel, aquaporin 4, was observed. Hypoperfused mice also demonstrated deficits in spatial working and reference memory tasks. Overall, gliovascular disruption is a prominent feature of this mouse, which could provide a useful model for early-phase testing of potential SVD treatment strategies. PMID:25669904

  11. Hyperhomocysteinemia disrupts retinal pigment epithelial structure and function with features of age-related macular degeneration.

    PubMed

    Ibrahim, Ahmed S; Mander, Suchreet; Hussein, Khaled A; Elsherbiny, Nehal M; Smith, Sylvia B; Al-Shabrawey, Mohamed; Tawfik, Amany

    2016-02-23

    The disruption of retinal pigment epithelial (RPE) function and the degeneration of photoreceptors are cardinal features of age related macular degeneration (AMD); however there are still gaps in our understanding of underlying biological processes. Excess homocysteine (Hcy) has been reported to be elevated in plasma of patients with AMD. This study aimed to evaluate the direct effect of hyperhomocysteinemia (HHcy) on structure and function of RPE. Initial studies in a mouse model of HHcy, in which cystathionine-β-synthase (cbs) was deficient, revealed abnormal RPE cell morphology with features similar to that of AMD upon optical coherence tomography (OCT), fluorescein angiography (FA), histological, and electron microscopic examinations. These features include atrophy, vacuolization, hypopigmentation, thickened basal laminar membrane, hyporeflective lucency, choroidal neovascularization (CNV), and disturbed RPE-photoreceptor relationship. Furthermore, intravitreal injection of Hcy per se in normal wild type (WT) mice resulted in diffuse hyper-fluorescence, albumin leakage, and CNV in the area of RPE. In vitro experiments on ARPE-19 showed that Hcy dose-dependently reduced tight junction protein expression, increased FITC dextran leakage, decreased transcellular electrical resistance, and impaired phagocytic activity. Collectively, our results demonstrated unreported effects of excess Hcy levels on RPE structure and function that lead to the development of AMD-like features.

  12. Hyperhomocysteinemia disrupts retinal pigment epithelial structure and function with features of age-related macular degeneration

    PubMed Central

    Ibrahim, Ahmed S.; Mander, Suchreet; Hussein, Khaled A.; Elsherbiny, Nehal M.; Smith, Sylvia B.; Al-Shabrawey, Mohamed; Tawfik, Amany

    2016-01-01

    The disruption of retinal pigment epithelial (RPE) function and the degeneration of photoreceptors are cardinal features of age related macular degeneration (AMD); however there are still gaps in our understanding of underlying biological processes. Excess homocysteine (Hcy) has been reported to be elevated in plasma of patients with AMD. This study aimed to evaluate the direct effect of hyperhomocysteinemia (HHcy) on structure and function of RPE. Initial studies in a mouse model of HHcy, in which cystathionine-β-synthase (cbs) was deficient, revealed abnormal RPE cell morphology with features similar to that of AMD upon optical coherence tomography (OCT), fluorescein angiography (FA), histological, and electron microscopic examinations. These features include atrophy, vacuolization, hypopigmentation, thickened basal laminar membrane, hyporeflective lucency, choroidal neovascularization (CNV), and disturbed RPE–photoreceptor relationship. Furthermore, intravitreal injection of Hcy per se in normal wild type (WT) mice resulted in diffuse hyper-fluorescence, albumin leakage, and CNV in the area of RPE. In vitro experiments on ARPE-19 showed that Hcy dose-dependently reduced tight junction protein expression, increased FITC dextran leakage, decreased transcellular electrical resistance, and impaired phagocytic activity. Collectively, our results demonstrated unreported effects of excess Hcy levels on RPE structure and function that lead to the development of AMD-like features. PMID:26885895

  13. Partial return yoke for MICE step IV and final step

    SciTech Connect

    Witte, H.; Plate, S.; Berg, J. S.; Tarrant, J.; Bross, A.

    2015-05-03

    This paper reports on the progress of the design and construction of a retro-fitted return yoke for the international Muon Ionization Cooling Experiment (MICE). MICE is a proof-of-principle experiment aiming to demonstrate ionization cooling experimentally. In earlier studies we outlined how a partial return yoke can be used to mitigate stray magnetic field in the experimental hall; we report on the progress of the construction of the partial return yoke for MICE Step IV. We also discuss an extension of the Partial Return Yoke for the final step of MICE; we show simulation results of the expected performance.

  14. Partial Return Yoke for MICE Step IV and Final Step

    SciTech Connect

    Witte, Holger; Plate, Stephen; Berg, J.Scott; Tarrant, Jason; Bross, Alan

    2015-06-01

    This paper reports on the progress of the design and construction of a retro-fitted return yoke for the international Muon Ionization Cooling Experiment (MICE). MICE is a proof-of-principle experiment aiming to demonstrate ionization cooling experimentally. In earlier studies we outlined how a partial return yoke can be used to mitigate stray magnetic field in the experimental hall; we report on the progress of the construction of the partial return yoke for MICE Step IV. We also discuss an extension of the Partial Return Yoke for the final step of MICE; we show simulation results of the expected performance.

  15. MMIC Phased Array Demonstrations with ACTS

    NASA Technical Reports Server (NTRS)

    Raquet, Charles A. (Compiler); Martzaklis, Konstantinos (Compiler); Zakrajsek, Robert J. (Compiler); Andro, Monty (Compiler); Turtle, John P.

    1996-01-01

    Over a one year period from May 1994 to May 1995, a number of demonstrations were conducted by the NASA Lewis Research Center (LeRC) in which voice, data, and/or video links were established via NASA's advanced communications technology satellite (ACTS) between the ACTS link evaluation terminal (LET) in Cleveland, OH, and aeronautical and mobile or fixed Earth terminals having monolithic microwave integrated circuit (MMIC) phased array antenna systems. This paper describes four of these. In one, a duplex voice link between an aeronautical terminal on the LeRC Learjet and the ACTS was achieved. Two others demonstrated duplex voice (and in one case video as well) links between the ACTS and an Army vehicle. The fourth demonstrated a high data rate downlink from ACTS to a fixed terminal. Array antenna systems used in these demonstrations were developed by LeRC and featured LeRC and Air Force experimental arrays using gallium arsenide MMIC devices at each radiating element for electronic beam steering and distributed power amplification. The single 30 GHz transmit array was developed by NASA/LeRC and Texas Instruments. The three 20 GHz receive arrays were developed in a cooperative effort with the Air Force Rome Laboratory, taking advantage of existing Air Force array development contracts with Boeing and Lockheed Martin. The paper describes the four proof-of-concept arrays and the array control system. The system configured for each of the demonstrations is described, and results are discussed.

  16. The optical properties and spectral features of malignant skin melanocytes in the terahertz frequency range

    NASA Astrophysics Data System (ADS)

    Goryachuk, A. A.; Begaeva, V. A.; Khodzitsky, M. K.; Truloff, A. S.

    2016-08-01

    The samples of cells of mice's melanocytes have been investigated. Their optical properties and spectral features were investigated by terahertz time-domain spectroscopy (TDS) in transmission mode. It was found that the optical properties of oncological melanocytes and normal cells are different and oncological cells have spectral features of absorption coefficient so it can be concluded that it is easy to discriminate mice's oncological skin melanocytes by using THz TDS.

  17. Endocrine alterations and signaling changes associated with declining ovarian function and advanced biological aging in follicle-stimulating hormone receptor haploinsufficient mice.

    PubMed

    Danilovich, Natalia; Javeshghani, Danesh; Xing, Weirong; Sairam, M Ram

    2002-08-01

    Reproductive aging in female mammals is characterized by a progressive decline in fertility due to loss of follicles and reduced ovarian steroidogenesis. In this study we examined some of the endocrine and signaling parameters that might contribute to a decrease in ovulation and reproductive performance of mice with haploinsufficiency of the FSH receptor (FSH-R). For this purpose we compared ovarian changes and hormone levels in FSH-R heterozygous (+/-) and wild-type mice of different ages (3, 7, and 12 mo). Hormone-induced ovulations in immature and 3-mo-old +/- mice were consistently lower. The number of corpora lutea (CL) were lower at 3 and 7 mo, and none were present in 1-yr-old +/- females. The plasma steroid and gonadotropin levels exhibited changes associated with typical ovarian aging. Plasma FSH and LH levels were higher in 7-mo-old +/- mice, but FSH levels continued to rise in both genotypes by 1 yr. Serum estradiol and progesterone were lower in +/- mice at all ages, and testosterone was several-fold higher in 7-mo-old and 1-yr-old +/- mice. Inhibin alpha (Western blot) appeared to be lower in +/- ovaries at all ages. FSH-R (FSH* binding) declined steadily from 3 mo and reaching the lowest point at 1 yr. LH receptor (LH* binding) was high in the 1-yr-old ovary, and expression was localized in the stroma and interstitial cells. Our findings demonstrate that haploinsufficiency of the FSH-R gene could cause premature exhaustion of the gonadal reserves previously noted in these mice. This is accompanied by age-related changes in the hypothalamic-pituitary axis. As these features in our FSH-R +/- mice resemble reproductive failure occurring in middle-age women, further studies in this model might provide useful insights into the mechanisms underlying ovarian aging.

  18. Pacific Northwest Resources Inventory Demonstration

    NASA Technical Reports Server (NTRS)

    Nichols, J. D.

    1976-01-01

    The Pacific Northwest Land Resource Inventory Demonstration project is designed to demonstrate to users from state and local agencies in Washington, Oregon, and Idaho the cost effective role that Landsat derived information can play in natural resource planning and management when properly supported by ground and aircraft data. The project has been organized into five main phases: (1) maps and overlays, (2) early digital image analysis, (3) demonstration of applications using interactive image analysis, (4) Landsat products and land resources information systems, and (5) documentation. The demonstration project has been applied to Washington forestry, water inventory in southern Idaho, and monitoring of tansy ragwort in western Oregon.

  19. Progress of the MICE experiment at RAL

    NASA Astrophysics Data System (ADS)

    Bonesini, M.

    2013-04-01

    The international Muon Ionization Cooling Experiment (MICE) will perform a systematic investigation of ionization cooling of a muon beam. The demonstration comprises one cell of the US Neutrino Factory Study II cooling channel. Results obtained on the construction of the beamline and its instrumentation (STEP I) will be reviewed, together with progress towards final measurements of ionization cooling (STEP IV and VI).

  20. Inherent design features of the GCFR

    SciTech Connect

    Medwid, W.; Breher, W.; Shenoy, A.; Elliott, R.

    1980-05-01

    This paper discusses several inherent design features of the GCFR that enhance its safety and presents analyses to demonstrate the degree of protection they provide. These features are a subset of a larger group of potential inherent features that form the third line of protection (LOP-3) for the GCFR. The function of LOP-3 is to demonstrate that the inherent response of the reactor system will limit core damage even if active cooling and shutdown systems in LOP-1 and LOP-2 fail. By providing this function with inherent features, which do not depend on active components and are self-controlling, an additional level of protection against common cause failure mechanisms is provided for both protected and unprotected events. The examples of LOP-3 discussed in this paper are natural circulation core cooling to the ultimate atmospheric heat sink and inherent reactor shutdown mechanisms.

  1. Contact hypersensitivity response to isophorone diisocyanate in mice

    SciTech Connect

    Stern, M.L.; Brown, T.A.; Brown, R.D.; Munson, A.E. )

    1989-09-01

    Isophorone diisocyanate was evaluated for its potential as a sensitizing agent for allergic contact hypersensitivity in mice. Female B6C3F1 mice were sensitized with 0.1, 0.3, and 1.0% isophorone diisocyanate and challenged with 3.0% isophorone diisocyanate. Doses of isophorone diisocyanate were selected from assays for primary irritancy. Mice received 20 microliters by direct dermal application, for 5 days, to sites prepared by shaving, dermabrading and, in some mice, with intra dermal injection of complete Freund's adjuvant. The rest period was 7 days. Measurement of the contact hypersensitivity response in mice was by radioisotopic assay two days after challenge and mouse ear swelling one and two days after challenge. Mice demonstrated statistically significant dose-dependent contact hypersensitivity responses to isophorone diisocyanate with or without adjuvant pretreatment.

  2. Bex1 knock out mice show altered skeletal muscle regeneration

    SciTech Connect

    Koo, Jae Hyung Smiley, Mark A.; Lovering, Richard M.; Margolis, Frank L.

    2007-11-16

    Bex1 and Calmodulin (CaM) are upregulated during skeletal muscle regeneration. We confirm this finding and demonstrate the novel finding that they interact in a calcium-dependent manner. To study the role of Bex1 and its interaction with CaM in skeletal muscle regeneration, we generated Bex1 knock out (Bex1-KO) mice. These mice appeared to develop normally and are fertile, but displayed a functional deficit in exercise performance compared to wild type (WT) mice. After intramuscular injection of cardiotoxin, which causes extensive and reproducible myotrauma followed by recovery, regenerating muscles of Bex1-KO mice exhibited elevated and prolonged cell proliferation, as well as delayed cell differentiation, compared to WT mice. Thus, our results provide the first evidence that Bex1-KO mice show altered muscle regeneration, and allow us to propose that the interaction of Bex1 with Ca{sup 2+}/CaM may be involved in skeletal muscle regeneration.

  3. Diet-induced obese mice retain endogenous leptin action.

    PubMed

    Ottaway, Nickki; Mahbod, Parinaz; Rivero, Belen; Norman, Lee Ann; Gertler, Arieh; D'Alessio, David A; Perez-Tilve, Diego

    2015-06-01

    Obesity is characterized by hyperleptinemia and decreased response to exogenous leptin. This has been widely attributed to the development of leptin resistance, a state of impaired leptin signaling proposed to contribute to the development and persistence of obesity. To directly determine endogenous leptin activity in obesity, we treated lean and obese mice with a leptin receptor antagonist. The antagonist increased feeding and body weight (BW) in lean mice, but not in obese models of leptin, leptin receptor, or melanocortin-4 receptor deficiency. In contrast, the antagonist increased feeding and BW comparably in lean and diet-induced obese (DIO) mice, an increase associated with decreased hypothalamic expression of Socs3, a primary target of leptin. These findings demonstrate that hyperleptinemic DIO mice retain leptin suppression of feeding comparable to lean mice and counter the view that resistance to endogenous leptin contributes to the persistence of DIO in mice.

  4. Knockout of Foxp2 disrupts vocal development in mice.

    PubMed

    Castellucci, Gregg A; McGinley, Matthew J; McCormick, David A

    2016-03-16

    The FOXP2 gene is important for the development of proper speech motor control in humans. However, the role of the gene in general vocal behavior in other mammals, including mice, is unclear. Here, we track the vocal development of Foxp2 heterozygous knockout (Foxp2+/-) mice and their wildtype (WT) littermates from juvenile to adult ages, and observe severe abnormalities in the courtship song of Foxp2+/- mice. In comparison to their WT littermates, Foxp2+/- mice vocalized less, produced shorter syllable sequences, and possessed an abnormal syllable inventory. In addition, Foxp2+/- song also exhibited irregular rhythmic structure, and its development did not follow the consistent trajectories observed in WT vocalizations. These results demonstrate that the Foxp2 gene is critical for normal vocal behavior in juvenile and adult mice, and that Foxp2 mutant mice may provide a tractable model system for the study of the gene's role in general vocal motor control.

  5. Microcephalia with mandibular and dental dysplasia in adult Zmpste24-deficient mice

    PubMed Central

    de Carlos, F; Varela, I; Germanà, A; Montalbano, G; Freije, J M P; Vega, J A; López-Otin, C; Cobo, J M

    2008-01-01

    ZMPSTE24 (also called FACE-1) is a zinc-metalloprotease involved in the post-translational processing of prelamin A to mature lamin A, a major component of the nuclear envelope. Mutations in the ZMPSTE24 gene or in that encoding its substrate prelamin A (LMNA) result in a series of human inherited diseases known collectively as laminopathies and showing regional or systemic manifestations (i.e. the Hutchinson–Gilford progeria syndrome). Typically, patients suffering some laminopathies show craniofacial or mandible anomalies, aberrant dentition or facial features characteristic of aged persons. To analyse whether Zmpste24−/– mice reproduce the cranial phenotype observed in humans due to mutations in ZMPSTE24or LMNA, we conducted a craniometric study based on micro-computer tomography (µCT) images. Furthermore, using simple radiology, µCT, µCT-densitometry and scanning electron microscopy, we analysed the mandible and the teeth from Zmpste24−/– mice. Finally, the structure of the lower incisor was investigated using an H&E technique. The results demonstrate that Zmpste24−/– mice are microcephalic and show mandibular and dental dysplasia affecting only the mandible teeth. In all cases, the lower incisor of mice lacking Zmpste24 was smaller than in control animals, showed cylindrical morphology and a transverse fissure at the incisal edge, and the pulpal cavity was severely reduced. Structurally, the dental layers were normally arranged but cellular layers were disorganized. The inferior molars showed a reduced cusp size. Taken together, these data strongly suggest that Zmpste24−/– mice represent a good model to analyse the craniofacial and teeth malformations characteristic of lamin-related pathologies, and might contribute to a better understanding of the molecular events underlying these diseases. PMID:19014358

  6. Status of MICE, the international Muon Ionization Cooling Experiment

    NASA Astrophysics Data System (ADS)

    Bross, Alan D.; MICE Collaboration

    2012-08-01

    The Muon Ionization Cooling Experiment (MICE) will demonstrate transverse muon ionization cooling and is thus a strategic R&D project for future muon facilities. It is under development at the Rutherford Appleton Laboratory in the United Kingdom.

  7. Understanding Statistics Using Computer Demonstrations

    ERIC Educational Resources Information Center

    Dunn, Peter K.

    2004-01-01

    This paper discusses programs that clarify some statistical ideas often discussed yet poorly understood by students. The programs adopt the approach of demonstrating what is happening, rather than using the computer to do the work for the students (and hide the understanding). The programs demonstrate normal probability plots, overfitting of…

  8. A Demonstration of Acid Rain

    ERIC Educational Resources Information Center

    Fong, Man Wai

    2004-01-01

    A demonstration showing acid rain formation is described. Oxides of sulfur and nitrogen that result from the burning of fossil fuels are the major pollutants of acid rain. In this demonstration, SO[subscript 2] gas is produced by the burning of matches. An acid-base indicator will show that the dissolved gas turns an aqueous solution acidic.

  9. Optics Demonstrations Using Cylindrical Lenses

    ERIC Educational Resources Information Center

    Ivanov, Dragia; Nikolov, Stefan

    2015-01-01

    In this paper we consider the main properties of cylindrical lenses and propose several demonstrational experiments that can be performed with them. Specifically we use simple glasses full of water to demonstrate some basic geometrical optics principles and phenomena. We also present some less standard experiments that can be performed with such…

  10. A Comprehensive General Chemistry Demonstration

    ERIC Educational Resources Information Center

    Sweeder, Ryan D.; Jeffery, Kathleen A.

    2013-01-01

    This article describes the use of a comprehensive demonstration suitable for a high school or first-year undergraduate introductory chemistry class. The demonstration involves placing a burning candle in a container adjacent to a beaker containing a basic solution with indicator. After adding a lid, the candle will extinguish and the produced…

  11. A Demonstration on Every Exam.

    ERIC Educational Resources Information Center

    Julian, Glenn M.

    1995-01-01

    Argues that inclusion of demonstrations on examinations increases students' ability to observe carefully the physical world around them, translate from observation in terms of models, and make quantitative estimates and physicist-type "back-of-the-envelope" calculations. Presents demonstration ideas covering the following topics: mechanics,…

  12. The "Mushroom Cloud" Demonstration Revisited

    ERIC Educational Resources Information Center

    Panzarasa, Guido; Sparnacci, Katia

    2013-01-01

    A revisitation of the classical "mushroom cloud" demonstration is described. Instead of aniline and benzoyl peroxide, the proposed reaction involves household chemicals such as alpha-pinene (turpentine oil) and trichloroisocyanuric acid ("Trichlor") giving an impressive demonstration of oxidation and combustion reactions that…

  13. A Demonstration of Sample Segregation

    ERIC Educational Resources Information Center

    Fritz, Mark D.; Brumbach, Stephen B.; Hartman, JudithAnn R.

    2005-01-01

    The demonstration of sample segregation, which is simple, and visually compelling illustrates the importance of sample handling for students studying analytical chemistry and environmental chemistry. The mixture used in this demonstration has two components, which have big particle size, and different colors, which makes the segregation graphic.

  14. Demonstrating Allotropic Modifications of Sulfur.

    ERIC Educational Resources Information Center

    McCarty, Jillian L.; Dragojlovic, Veljko

    2002-01-01

    Shows how a common demonstration that consists of slowly heating sulfur powder in a test tube to illustrate sulfur's allotropic modifications can convince students of conclusions about the moon Io which they often find surprising. Describes the demonstration in full. (Author/MM)

  15. Rocket Ignition Demonstrations Using Silane

    NASA Technical Reports Server (NTRS)

    Pal, Sibtosh; Santoro, Robert; Watkins, William B.; Kincaid, Kevin

    1998-01-01

    Rocket ignition demonstration tests using silane were performed at the Penn State Combustion Research Laboratory. A heat sink combustor with one injection element was used with gaseous propellants. Mixtures of silane and hydrogen were used as fuel, and oxygen was used as oxidizer. Reliable ignition was demonstrated using fuel lead and and a swirl injection element.

  16. Three Mechanical Demonstrations of Chaos.

    ERIC Educational Resources Information Center

    Ehrlich, Robert

    1990-01-01

    Describes three demonstrations showing chaotic motion, which makes long-term prediction impossible. Discusses the apparatus for the demonstrations and procedures for illustrating chaotic motion of pendulum, balls rolling in a double potential well, and a ball rolling on a balanced beam. (YP)

  17. Teaching and Demonstrating Classical Conditioning.

    ERIC Educational Resources Information Center

    Sparrow, John; Fernald, Peter

    1989-01-01

    Discusses classroom demonstrations of classical conditioning and notes tendencies to misrepresent Pavlov's procedures. Describes the design and construction of the conditioner that is used for demonstrating classical conditioning. Relates how students experience conditioning, generalization, extinction, discrimination, and spontaneous recovery.…

  18. Buried Waste Integrated Demonstration: Selection of potential demonstration locations

    SciTech Connect

    Arrenholz, D.A.; Knight, J.L.

    1991-11-01

    The first step towards identifying primary Buried Waste Integrated Demonstration locations is the selection of potential demonstration sites within the Subsurface Disposal Area. The sites selected are Pits 4, 5, 6, and 9, containing transuranic waste of Rocky Flats origin, the Acid Pit, and Pad A. The criteria and methodology for selection of these sites, as well as a description of the wastes present in each area, are included in this report. At a later date, technology-specific demonstration locations will be selected from these six potential sites. The selected locations will be used as necessary to demonstrate technologies whose potential abilities may be optimal on waste forms present at these identified locations.

  19. Reliability prediction for the SLOWPOKE demonstration reactor building heating demonstration

    SciTech Connect

    Winfield, D.J. ); Cole, D.; Bennett, L.G.I.

    1991-01-01

    The SLOWPOKE demonstration reactor (SDR) is a new prototype heating reactor, nominally 2 MW(thermal), developed by Atomic Energy of Canada Limited at the Whiteshell Laboratories. This project is part of a program to demonstrate the concept of supplying low-grade heat up to 10 MW(thermal) to localized district heating grids from an unpressurized nuclear heating source using a low-enriched, CANDU-type fuel. Reactor thermal-hydraulic and core physics commissioning experiments and analysis up to 1.2 MW(thermal) were completed in 1990. This report presents that part of the safety and reliability analysis program that provided reliability predictions for the associated building heating demonstration (BHD) systems. Proposed upgrades to test the 10-MW(thermal) core design have delayed the long-term heat demonstration commissioning tests.

  20. Tested Demonstrations. A Chemiluminescence Demonstration - Oxalyl Chloride Oxidation.

    ERIC Educational Resources Information Center

    Gilber, George L., Ed.

    1979-01-01

    This inexpensive, effective chemiluminescence demonstration requires minimal preparation. It is based on the oxidation of oxalyl chloride by hydrogen peroxide in the presence of an appropriate fluorescent sensitizer. The reaction mechanism is not completely understood. (BB)

  1. Tested Demonstrations: A Simple Demonstration of Reversible Oxygenation.

    ERIC Educational Resources Information Center

    Kildahl, Nicholas K.

    1983-01-01

    Materials needed, reaction involved, and potential hazards are provided for a demonstration of reversible oxygenation. Also discusses the importance of the reaction in biological systems, focusing on hemoglobin/myoglobin and their function in mammals. (JM)

  2. Ontology patterns for complex topographic feature yypes

    USGS Publications Warehouse

    Varanka, Dalia E.

    2011-01-01

    Complex feature types are defined as integrated relations between basic features for a shared meaning or concept. The shared semantic concept is difficult to define in commonly used geographic information systems (GIS) and remote sensing technologies. The role of spatial relations between complex feature parts was recognized in early GIS literature, but had limited representation in the feature or coverage data models of GIS. Spatial relations are more explicitly specified in semantic technology. In this paper, semantics for topographic feature ontology design patterns (ODP) are developed as data models for the representation of complex features. In the context of topographic processes, component assemblages are supported by resource systems and are found on local landscapes. The topographic ontology is organized across six thematic modules that can account for basic feature types, resource systems, and landscape types. Types of complex feature attributes include location, generative processes and physical description. Node/edge networks model standard spatial relations and relations specific to topographic science to represent complex features. To demonstrate these concepts, data from The National Map of the U. S. Geological Survey was converted and assembled into ODP.

  3. Narp knockout mice show normal reactivity to novelty but attenuated recovery from neophobia.

    PubMed

    Blouin, Ashley M; Lee, Jongah J; Tao, Bo; Smith, Dani R; Johnson, Alexander W; Baraban, Jay M; Reti, Irving M

    2013-11-15

    Narp knockout (KO) mice demonstrate cognitive inflexibility and addictive behavior, which are associated with abnormal reactivity to a novel stimulus. To assess reactivity to novelty, we tested Narp KO and wild-type (WT) mice on a neophobia procedure. Both Narp KO and WT mice showed a similar decrease in consumption upon initial exposure to a novel flavor, but Narp KO mice did not increase consumption with subsequent exposures to the novel flavor like the WT mice. Therefore, Narp KO mice do not have abnormal reactivity to novelty but show deficits in adapting behavior to reflect the updated value of a stimulus.

  4. Cryovolcanic Features on Titan

    NASA Astrophysics Data System (ADS)

    Lopes, R. M. C.; Stofan, E. R.; Kirk, R. L.; Mitchell, K. L.; LeGall, A.; Barnes, J. W.; Hayes, A.; Kargel, J.; Radebaugh, J.; Janssen, M. A.; Neish, C. D.; Wood, C.; Wall, S. D.; Lunine, J. I.; Malaska, M. J.

    2013-09-01

    We present evidence to support the cryovolcanic origin of some features, which includes the deepest pit known on Titan (Sotra Patera) and some of the highest mountains (Doom and Erebor Montes). We interpret this region to be a cryovolcanic complex of multiple cones, craters, and flows. Elsewhere, a circular feature, approximately 100 km across, is morphologically similar to a laccolith, showing a cross pattern interpreted to be extensional fractures. However, we find that some other previously supposed cryovolcanic features were likely formed by other processes. We discuss implications for eruption style and composition of cryovolcanism on Titan. Our analysis shows the great value of combining data sets when interpreting Titan's geology and in particular stresses the value of topographic data.

  5. Three featured plenary sessions

    NASA Astrophysics Data System (ADS)

    2012-07-01

    The conference included three plenary sessions. The plenary on Governance, Security, Economy, and the Ecosystem of the Changing Arctic featured Vera Alexander, president, Arctic Research Consortium of the U.S.; Alan Thornhill, chief environmental officer, U.S. Department of the Interior's Bureau of Ocean Energy Management; and Fran Ulmer, chair, U.S. Arctic Research Commission. A plenary on the U.N. Convention on the Law of the Sea featured Ambassador David Balton, deputy assistant secretary for oceans and fisheries, U.S. Department of State; and Rear Admiral Frederick Kenney Jr., judge advocate general and chief counsel, U.S. Coast Guard. The plenary on Science and the 21st Century featured Phil Keslin, chief technology officer, small lab within Google.

  6. Substation fire protection features

    SciTech Connect

    Hausheer, T.G.

    1995-10-01

    This paper describes Commonwealth Edison`s (ComEd) approach to substation fire protection. Substation fires can have a major operational, financial, as well as political impact on a utility. The overall Company philosophy encompasses both active and passive fire protection features to provide prompt detection, notification, and confinement of fire and its by-products. Conservatively designed smoke detection systems and floor and wall penetration seals form the backbone of this strategy. The Company has implemented a program to install these features in new and existing substations. Thus far these measures have been successful in mitigating the consequences of substation fires.

  7. Escalator design features evaluation

    NASA Technical Reports Server (NTRS)

    Zimmerman, W. F.; Deshpande, G. K.

    1982-01-01

    Escalators are available with design features such as dual speed (90 and 120 fpm), mat operation and flat steps. These design features were evaluated based on the impact of each on capital and operating costs, traffic flow, and safety. A human factors engineering model was developed to analyze the need for flat steps at various speeds. Mat operation of escalators was found to be cost effective in terms of energy savings. Dual speed operation of escalators with the higher speed used during peak hours allows for efficient operation. A minimum number of flat steps required as a function of escalator speed was developed to ensure safety for the elderly.

  8. Robust feature detection using sonar sensors for mobile robots

    NASA Astrophysics Data System (ADS)

    Choi, Jinwoo; Ahn, Sunghwan; Chung, Wan Kyun

    2005-12-01

    Sonar sensor is an attractive tool for the SLAM of mobile robot because of their economic aspects. This cheap sensor gives relatively accurate range readings if disregarding angular uncertainty and specular reflections. However, these defects make feature detection difficult for the most part of the SLAM. This paper proposed a robust sonar feature detection algorithm. This algorithm gives feature detection methods for both point features and line features. The point feature detection method was based on the TBF scheme. Moreover, three additional processes improved the performance of feature detection as follows; 1) stable intersections, 2) efficient sliding window update and 3) removal of the false point features on the wall. The line feature detection method was based on the basic property of adjacent sonar sensors. Along the line feature, three adjacent sonar sensors gave similar range readings. Using this sensor property, it proposed a novel algorithm for line feature detection, which is simple and the feature can be obtained by using only current sensor data. The proposed feature detection algorithm gives a good solution for the SLAM of mobile robots because it gives accurate feature information for both the point and line features even with sensor errors. Furthermore, a sufficient number of features are available to correct mobile robot pose. Experimental results for point feature and line feature detection demonstrate the performance of the proposed algorithm in a home-like environment.

  9. Metabolomics reveals significant impairments in the immune system of the APP/PS1 transgenic mice of Alzheimer's disease.

    PubMed

    González-Domínguez, Raúl; García-Barrera, Tamara; Vitorica, Javier; Gómez-Ariza, José Luis

    2015-02-01

    Inflammatory processes and other failures related to the immune system are common features associated with Alzheimer's disease (AD), in both brain and the peripheral system. Thus, the study of the main organs of the immune system may have a great potential for the elucidation of pathological mechanisms underlying these abnormalities. This is the first metabolomic investigation performed in spleen and thymus from transgenic mice of AD. Tissues were fingerprinted using a metabolomic platform comprising GC-MS and ultra-HPLC-MS. Multivariate statistics demonstrated significant differences in numerous metabolites between the APP/PS1 mice and wild-type controls, and it was proven that multiple biochemical pathways are disturbed in these organs including abnormal metabolism of phospholipids, energy deficiencies, altered homeostasis of amino acids, oxidative stress, and others. Therefore, these findings highlight the importance of the proper metabolic functioning of peripheral immune system in the development of neurodegenerative disorders such as AD.

  10. Offsite demonstrations for MWLID technologies

    SciTech Connect

    Williams, C.; Gruebel, R.

    1995-04-01

    The goal of the Offsite Demonstration Project for Mixed Waste Landfill Integrated Demonstration (MWLID)-developed environmental site characterization and remediation technologies is to facilitate the transfer, use, and commercialization of these technologies to the public and private sector. The meet this goal, the project identified environmental restoration needs of mixed waste and/or hazardous waste landfill owners (Native American, municipal, DOE, and DoD); documenting potential demonstration sites and the contaminants present at each site; assessing the environmental regulations that would effect demonstration activities; and evaluating site suitability for demonstrating MWLID technologies at the tribal and municipal sites identified. Eighteen landfill sites within a 40.2-km radius of Sandia National Laboratories are listed on the CERCLIS Site/Event Listing for the state of New Mexico. Seventeen are not located within DOE or DoD facilities and are potential offsite MWLID technology demonstration sites. Two of the seventeen CERCLIS sites, one on Native American land and one on municipal land, were evaluated and identified as potential candidates for off-site demonstrations of MWLID-developed technologies. Contaminants potentially present on site include chromium waste, household/commercial hazardous waste, volatile organic compounds, and petroleum products. MWLID characterization technologies applicable to these sites include Magnetometer Towed Array, Cross-borehole Electromagnetic Imaging, SitePlanner {trademark}/PLUME, Hybrid Directional Drilling, Seamist{trademark}/Vadose Zone Monitoring, Stripping Analyses, and x-ray Fluorescence Spectroscopy for Heavy Metals.

  11. Crafting a Gauss Gun Demonstration

    NASA Astrophysics Data System (ADS)

    Blodgett, Matthew E.; Blodgett, E. D.

    2006-12-01

    A Gauss Gun launches a ferromagnetic projectile using a pulsed electromagnet. This demonstration provides a nice counterpoint to the popular Thompson's jumping ring demonstration, which launches a nonferromagnetic ring via repulsion of an induced current. The pulsed current must be short enough in duration so that the projectile is not retarded by lingering current in the launch solenoid, but also large enough to provide a suitably impressive velocity. This project involved an iterative design process, as we worked through balancing all the different design criteria. We recommend it as a very nice electronics design project which will produce a very portable and enjoyable demonstration. AAPT sponsor Earl Blodgett.

  12. Notional Airspace Operations Demonstration Plan

    NASA Technical Reports Server (NTRS)

    Trongale, Nicholas A.

    2006-01-01

    The airspace operations demonstration (AOD) is intended to show that the Access 5 Step 1 functional requirements can be met. The demonstration will occur in two phases. The initial on-range phase will be carried out in restricted airspace to demonstrate the cooperative collision avoidance (CCA) functional requirements and to provide risk-reduction for the AOD by allowing the test team to rehearse some elements of the demonstration mission. The CCA system to be used in these flights is based on Automatic Dependent Surveillance-Broadcast (ADS-B) which is a commercially-available system by which airplanes constantly broadcast their current position and altitude to other aircraft and ground resources over a dedicated radio datalink. The final phase will occur in the national airspace (NAS) and will be the formal demonstration of the remainder of the proposed functional requirements. The general objectives of the AOD are as follows: (1) Demonstrate that the UAS can aviate in the NAS (2) Demonstrate that the UAS can navigate in the NAS (3) Demonstrate that the UAS can communicate with the NAS (4) Demonstrate that the UAS can perform selected collision avoidance functions in the NAS (5) Demonstrate that the UAS can evaluate and avoid weather conflicts in the NAS (6) Demonstrate that the UAS can provide adequate command and control in the NAS In addition to the stated objectives, there are a number of goals for the flight demonstration. The demo can be accomplished successfully without achieving these goals, but these goals are to be used as a guideline for preparing for the mission. The goals are: (1) Mission duration of at least 24 hours (2) Loiter over heavy traffic to evaluate the data block issue identified during the Access 5 Airspace Operations Simulations (3) Document the contingency management process and lessons learned (4) Document the coordination process for Ground Control Stations (GCS) handoff (5) Document lessons learned regarding the process of flying in

  13. Optical Communications and Sensor Demonstration

    NASA Technical Reports Server (NTRS)

    Martinez, Andres; Petro, Andrew

    2015-01-01

    The Optical Communications and Sensor Demonstration (OCSD) project addresses two cross-cutting capabilities of value to many future small spacecraft missions: high-speed optical transmission of data and small spacecraft proximity operations. Optical data rates demonstrated by OCSD are expected to be 200 megabits persecond (Mbs) or higher, a factor of 100 increase over current high-end CubeSat communications systems. The proximity sensors developed for this mission enable relative position measurement between two small satellites - a capability not previously demonstrated.

  14. Integrated Education. Feature Issue.

    ERIC Educational Resources Information Center

    York, Jennifer, Ed.; Vandercook, Terri, Ed.

    1988-01-01

    This "feature issue" provides various perspectives on a number of integrated education topics, including successful integration practices and strategies, the changing roles of teachers, the appropriate role of research, the history and future of integrated education, and the realization of dreams of life in the mainstream for children with severe…

  15. Searchable solar feature catalogues

    NASA Astrophysics Data System (ADS)

    Zharkova, V. V.; Aboudarham, J.; Zharkov, S.; Ipson, S. S.; Benkhalil, A. K.; Fuller, N.

    The searchable Solar Feature Catalogues (SFCs) are developed from digitized solar images using automated pattern recognition techniques. The techniques were applied for the detection of sunspots, active regions, filaments and line-of-sight magnetic neutral lines in automatically standardized full disk solar images in Ca II K1, Ca II K3 and Ha lines taken at the Paris-Meudon Observatory and white light images and magnetograms from SOHO/MDI. The results of the automated recognition were verified with manual synoptic maps and available statistical data that revealed good detection accuracy. Based on the recognized parameters, a structured database of Solar Feature Catalogues was built on a MySQL server for every feature and published with various pre-designed search pages on the Bradford University web site http://www.cyber.brad.ac.uk/egso/SFC/. The SFCs with nine year coverage (1996-2004) is to be used for deeper investigation of the feature classification and solar activity forecast.

  16. Assistive Technologies, Feature Issue.

    ERIC Educational Resources Information Center

    Wobschall, Rachel, Ed.; Lakin, Charlie, Ed.

    1995-01-01

    This feature issue of a newsletter on community integration of individuals with developmental disabilities considers the role of assistive technologies. It describes efforts to utilize consumer direction, public policy, creativity, energy, and professional know-how in the pursuit of technology-based opportunities to enhance community inclusion,…

  17. Main features of meiosis

    SciTech Connect

    1993-12-31

    Chapter 17, outlines the main features of meiosis, beginning with its significance and proceeding through the meiotic stages. Meiosis is the most important modification of mitosis because it is the reduction division that gives rise to the haploid generation in the life cycle. 17 refs., 6 figs.

  18. Development of a Computational High-Throughput Tool for the Quantitative Examination of Dose-Dependent Histological Features

    PubMed Central

    Nault, Rance; Colbry, Dirk; Brandenberger, Christina; Harkema, Jack R.; Zacharewski, Timothy R.

    2015-01-01

    High-resolution digitalizing of histology slides facilitates the development of computational alternatives to manual quantitation of features of interest. We developed a MATLAB-based quantitative histological analysis tool (QuHAnT) for the high-throughput assessment of distinguishable histological features. QuHAnT validation was demonstrated by comparison with manual quantitation using liver sections from mice orally gavaged with sesame oil vehicle or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 0.001–30 µg/kg) every 4 days for 28 days, which elicits hepatic steatosis with mild fibrosis. A quality control module of QuHAnT reduced the number of quantifiable Oil Red O (ORO)-stained images from 3,123 to 2,756. Increased ORO staining was measured at 10 and 30 µg/kg TCDD with a high correlation between manual and computational volume densities (Vv), although the dynamic range of QuHAnT was 10-fold greater. Additionally, QuHAnT determined the size of each ORO vacuole, which could not be accurately quantitated by visual examination or manual point counting. PicroSirius Red quantitation demonstrated superior collagen deposition detection due to the ability to consider all images within each section. QuHAnT dramatically reduced analysis time and facilitated the comprehensive assessment of features improving accuracy and sensitivity and represents a complementary tool for tissue/cellular features that are difficult and tedious to assess via subjective or semiquantitative methods. PMID:25274660

  19. Demonstrating Forces between Parallel Wires.

    ERIC Educational Resources Information Center

    Baker, Blane

    2000-01-01

    Describes a physics demonstration that dramatically illustrates the mutual repulsion (attraction) between parallel conductors using insulated copper wire, wooden dowels, a high direct current power supply, electrical tape, and an overhead projector. (WRM)

  20. CT Demonstration of Caput Medusae

    ERIC Educational Resources Information Center

    Weber, Edward C.; Vilensky, Joel A.

    2009-01-01

    Maximum intensity and volume rendered CT displays of caput medusae are provided to demonstrate both the anatomy and physiology of this portosystemic shunt associated with portal hypertension. (Contains 2 figures.)

  1. Classroom Demonstrations of Auditory Perception.

    ERIC Educational Resources Information Center

    Haws, LaDawn; Oppy, Brian J.

    2002-01-01

    Presents activities to help students gain understanding about auditory perception. Describes demonstrations that cover topics, such as sound localization, wave cancellation, frequency/pitch variation, and the influence of media on sound propagation. (CMK)

  2. Demonstration of the Fenton Reaction

    ERIC Educational Resources Information Center

    Luehrs, Dean C.; Roher, Alex E.

    2007-01-01

    The study demonstrates the Fenton reaction, which is carried out using the Fenton reagent that is used for groundwater and soil remediation. The Fenton reaction can be implicated in DNA damage, Alzheimer's disease, cardiovascular disease and ageing in general.

  3. Classroom Demonstrations of Polymer Principles.

    ERIC Educational Resources Information Center

    Rodriguez, F.

    1990-01-01

    Classroom demonstrations of selected mechanical properties of polymers are described that can be used to make quantitative measurements. Stiffness, strength, and extensibility are mechanical properties used to distinguish one polymer from another. (KR)

  4. Status of the Majorana Demonstrator

    DOE PAGES

    Cuesta, C.; Abgrall, N.; Arnquist, I. J.; Avignone, III, F. T.; Barabash, A. S.; Bertrand, F. E.; Brudanin, V.; Busch, M.; Buuck, M.; Byram, D.; et al

    2015-08-06

    The Majorana Collaboration is constructing the Majorana Demonstrator, an ultra-low background, 40-kg modular high purity Ge detector array to search for neutrinoless double-beta decay in 76Ge. In view of the next generation of tonne-scale Ge-based neutrinoless double-beta decay searches that will probe the neutrino mass scale in the inverted-hierarchy region, a major goal of the Demonstrator is to demonstrate a path forward to achieving a background rate at or below 1 count/tonne/year in the 4 keV region of interest around the Q-value at 2039 keV. Lastly, the current status of the Demonstrator is discussed, as are plans for its completion.

  5. Cubesat Proximity Operations Demonstration (CPOD)

    NASA Technical Reports Server (NTRS)

    Villa, Marco; Martinez, Andres; Petro, Andrew

    2015-01-01

    The CubeSat Proximity Operations Demonstration (CPOD) project will demonstrate rendezvous, proximity operations and docking (RPOD) using two 3-unit (3U) CubeSats. Each CubeSat is a satellite with the dimensions 4 inches x 4 inches x 13 inches (10 centimeters x 10 centimeters x 33 centimeters) and weighing approximately 11 pounds (5 kilograms). This flight demonstration will validate and characterize many new miniature low-power proximity operations technologies applicable to future missions. This mission will advance the state of the art in nanosatellite attitude determination,navigation and control systems, in addition to demonstrating relative navigation capabilities.The two CPOD satellites are scheduled to be launched together to low-Earth orbit no earlier than Dec. 1, 2015.

  6. Rubens Flame-Tube Demonstration.

    ERIC Educational Resources Information Center

    Ficken, George W.; Stephenson, Francis C.

    1979-01-01

    Investigates and explains the phenomenon associated with Rubens flame-tube demonstration, specifically the persistance of flames at regular intervals along the tube for few minutes after the gas is turned off. (GA)

  7. Teacher Training: The Demonstration Lesson

    ERIC Educational Resources Information Center

    Moore, Alan C.

    1977-01-01

    A teacher training technique is discussed involving a demonstration class given by a local teacher and observed by prospective teachers. After the class a discussion is held analyzing lesson content and teaching techniques. (CHK)

  8. Status of the Majorana Demonstrator

    SciTech Connect

    Cuesta, C.; Abgrall, N.; Arnquist, I. J.; Avignone, III, F. T.; Barabash, A. S.; Bertrand, F. E.; Brudanin, V.; Busch, M.; Buuck, M.; Byram, D.; Caldwell, A. S.; Chan, Y. -D.; Christofferson, C. D.; Detwiler, J. A.; Efremenko, Yu.; Ejiri, H.; Elliott, S. R.; Galindo-Uribarri, A.; Giovanetti, G. K.; Goett, J.; Green, M. P.; Gruszko, J.; Guinn, I. S.; Guiseppe, V. E.; Henning, R.; Hoppe, E. W.; Howard, S.; Howe, M. A.; Jasinski, B. R.; Keeter, K. J.; Kidd, M. F.; Konovalov, S. I.; Kouzes, R. T.; LaFerriere, B. D.; Leon, J.; MacMullin, J.; Martin, R. D.; Meijer, S. J.; Mertens, S.; Orrell, J. L.; O'Shaughnessy, C.; Overman, N. R.; Poon, A. W. P.; Radford, D. C.; Rager, J.; Rielage, K.; Robertson, R. G. H.; Romero-Romero, E.; Schmitt, C.; Shanks, B.; Shirchenko, M.; Snyder, N.; Suriano, A. M.; Tedeschi, D.; Timkin, V.; Trimble, J. E.; Varner, R. L.; Vasilyev, S.; Vetter, K.; Vorren, K.; White, B. R.; Wilkerson, J. F.; Wiseman, C.; Xu, W.; Yakushev, E.; Yu, C. -H.; Yumatov, V.

    2015-08-06

    The Majorana Collaboration is constructing the Majorana Demonstrator, an ultra-low background, 40-kg modular high purity Ge detector array to search for neutrinoless double-beta decay in 76Ge. In view of the next generation of tonne-scale Ge-based neutrinoless double-beta decay searches that will probe the neutrino mass scale in the inverted-hierarchy region, a major goal of the Demonstrator is to demonstrate a path forward to achieving a background rate at or below 1 count/tonne/year in the 4 keV region of interest around the Q-value at 2039 keV. Lastly, the current status of the Demonstrator is discussed, as are plans for its completion.

  9. Status of the Majorana Demonstrator

    SciTech Connect

    Cuesta, C.; Abgrall, N.; Arnquist, Isaac J.; Avignone, Frank T.; Barabash, Alexander S.; Bertrand, F.; Brudanin, V.; Busch, Matthew; Buuck, M.; Byram, D.; Caldwell, A. S.; Chan, Yuen-Dat; Christofferson, Cabot-Ann; Detwiler, Jason A.; Efremenko, Yuri; Ejiri, H.; Elliott, S. R.; Galindo-Uribarri, A.; Giovanetti, G. K.; Goett, J.; Green, M. P.; Gruszko, J.; Guinn, I.; Guiseppe, V. E.; Henning, R.; Hoppe, Eric W.; Howard, Stanley; Howe, M. A.; Jasinski, B. R.; Keeter, K.; Kidd, M. F.; Konovalov, S.; Kouzes, Richard T.; Laferriere, Brian D.; Leon, Jonathan D.; MacMullin, J.; Martin, R. D.; Meijer, S. J.; Mertens, S.; Orrell, John L.; O'Shaughnessy, C.; Overman, Nicole R.; Poon, Alan; Radford, D. C.; Rager, J.; Rielage, Keith; Robertson, R. G. H.; Romero-Romero, E.; Schmitt, C.; Shanks, B.; Shirchenko, M.; Snyder, N.; Suriano, Anne-Marie; Tedeschi, D.; Timkin, V.; Trimble, J. E.; Varner, R. L.; Vasilyev, Sergey; Vetter, Kai; Vorren, Kris R.; White, Brandon R.; Wilkerson, J. F.; Wiseman, C.; Xu, W.; Yakushev, E.; Yu, Chang-Hong; Yumatov, Vladimir

    2015-06-09

    The Majorana Collaboration is constructing the Majorana Demonstrator, an ultra-low background, 40-kg modular high purity Ge detector array to search for neutrinoless double-beta decay in 76Ge. In view of the next generation of tonne-scale Ge-based neutrinoless double-beta decay searches that will probe the neutrino mass scale in the inverted hierarchy region, a major goal of the Demonstrator is to demonstrate a path forward to achieving a background rate at or below 1 count/tonne/year in the 4 keV region of interest around the Q-value at 2039 keV. The current status of the Demonstrator is discussed, as are plans for its completion.

  10. Novel Third-Law Demonstration.

    ERIC Educational Resources Information Center

    Lonc, William

    1995-01-01

    Presents an easy method to demonstrate Third-Law interactions using identical button magnets sliding along a smooth (nonmagnetic) knitting needle. Explains the gravitational and magnetic interactions in the case of horizontal and vertical positions of the needle. (JRH)

  11. MICE Spectrometer Solenoid Magnetic Field Measurements

    SciTech Connect

    Leonova, M.

    2013-09-01

    The Muon Ionization Cooling Experiment (MICE) is designed to demonstrate ionization cooling in a muon beam. Its goal is to measure a 10% change in transverse emittance of a muon beam going through a prototype Neutrino Factory cooling channel section with an absolute measurement accuracy of 0.1%. To measure emittances, MICE uses two solenoidal spectrometers, with Solenoid magnets designed to have 4 T fields, uniform at 3 per mil level in the tracking volumes. Magnetic field measurements of the Spectrometer Solenoid magnet SS2, and analysis of coil parameters for input into magnet models will be discussed.

  12. Slant Borehole Demonstration Summary Report

    SciTech Connect

    GARDNER, M.G.

    2000-07-19

    This report provides a summary of the demonstration project for development of a slant borehole to retrieve soil samples from beneath the SX-108 single-shell tank. It provides a summary of the findings from the demonstration activities and recommendations for tool selection and methods to deploy into the SX Tank Farm. Daily work activities were recorded on Drilling and Sampling Daily Work Record Reports. The work described in this document was performed during March and April 2000.

  13. Edison Demonstration of Smallsat Networks

    NASA Technical Reports Server (NTRS)

    Westley, Deborah; Martinez, Andres; Petro, Andrew

    2015-01-01

    The goal of NASA's Edison Demonstration of Smallsat Networks (EDSN) mission is to demonstrate interactive satellite swarms capable of collecting, exchanging and transmitting multi-point scientific measurements. Satellite swarms enable a wide array of scientific, commercial and academic research not achievable with a single satellite. The EDSN satellites are scheduled to be launched into space as secondary payloads on the first flight of the Super Strypi launch vehicle no earlier than Oct. 29, 2015.

  14. Lunar Water Resource Demonstration (LWRD)

    NASA Technical Reports Server (NTRS)

    Muscatello, Anthony C.

    2009-01-01

    Lunar Water Resource Demonstration (LWRD) is part of RESOLVE (Regolith and Environment Science & Oxygen and Lunar Volatile Extraction). RESOLVE is an ISRU ground demonstration: (1) A rover to explore a permanently shadowed crater at the south or north pole of the Moon (2) Drill core samples down to 1 meter (3) Heat the core samples to 150C (4) Analyze gases and capture water and/or hydrogen evolved (5) Use hydrogen reduction to extract oxygen from regolith

  15. Yo-Yo Pull Demonstration

    ERIC Educational Resources Information Center

    Layton, William

    2013-01-01

    A popular demonstration involves placing a yo-yo on a level table and gently pulling the string horizontally when it is wrapped to come out below the center of the yo-yo's axis. Students are then asked to predict which way the yo-yo will move. A similar demonstration is performed with a tricycle by pulling forward on a pedal with the pedal down in…

  16. Wave rotor demonstrator engine assessment

    NASA Technical Reports Server (NTRS)

    Snyder, Philip H.

    1996-01-01

    The objective of the program was to determine a wave rotor demonstrator engine concept using the Allison 250 series engine. The results of the NASA LERC wave rotor effort were used as a basis for the wave rotor design. A wave rotor topped gas turbine engine was identified which incorporates five basic requirements of a successful demonstrator engine. Predicted performance maps of the wave rotor cycle were used along with maps of existing gas turbine hardware in a design point study. The effects of wave rotor topping on the engine cycle and the subsequent need to rematch compressor and turbine sections in the topped engine were addressed. Comparison of performance of the resulting engine is made on the basis of wave rotor topped engine versus an appropriate baseline engine using common shaft compressor hardware. The topped engine design clearly demonstrates an impressive improvement in shaft horsepower (+11.4%) and SFC (-22%). Off design part power engine performance for the wave rotor topped engine was similarly improved including that at engine idle conditions. Operation of the engine at off design was closely examined with wave rotor operation at less than design burner outlet temperatures and rotor speeds. Challenges identified in the development of a demonstrator engine are discussed. A preliminary design was made of the demonstrator engine including wave rotor to engine transition ducts. Program cost and schedule for a wave rotor demonstrator engine fabrication and test program were developed.

  17. Tight skin 2 mice exhibit a novel time line of events leading to increased extracellular matrix deposition and dermal fibrosis.

    PubMed

    Long, Kristen B; Artlett, Carol M; Blankenhorn, Elizabeth P

    2014-09-01

    The tight skin 2 (Tsk2) mouse model of systemic sclerosis (SSc) has many features of the human disease including tight skin, fibrosis, extracellular matrix abnormalities, and reported antinuclear antibodies (ANA). Here we report that Tsk2/+ mice develop excess dermal fibrosis with age, as skin is not significantly fibrotic until 10 weeks, a full eight weeks after the development of the physical tight skin phenotype. Concomitantly with the tight skin phenotype at two weeks of age, Tsk2/+ mice demonstrate increased levels of total transforming growth factor beta 1 (TGF-β1) and excessive accumulation of dermal elastic fibers. The increase in elastic fibers is not responsible for tight skin, however, because Tsk2/+ mice genetically engineered to lack skin elastic fibers nevertheless have tight skin and fibrosis. Finally, about two months after the first measurable increases of total collagen, a portion of Tsk2/+ mice produce ANAs, but at a similar level to wild-type littermates. The timeline of disease development in the Tsk2/+ mouse shows that fibrosis is progressive, with elastic fiber alterations and TGF-β1 over-production occurring at least two months before bona fide fibrosis, that is not dependent on ANA production.

  18. Temporal profiles of neuronal degeneration, glial proliferation, and cell death in hNFL(+/+) and NFL(-/-) mice.

    PubMed

    McLean, Jesse R; Sanelli, Teresa R; Leystra-Lantz, Cheryl; He, Bei Ping; Strong, Michael J

    2005-10-01

    Neurofilament (NF) aggregate formation within motor neurons is a pathological hallmark of both the sporadic and familial forms of amyotrophic lateral sclerosis (ALS). The relationship between aggregate formation and both microglial and astrocytic proliferation, as well as additional neuropathological features of ALS, is unknown. To examine this, we have used transgenic mice that develop NF aggregates, through either a lack of the low-molecular-weight NF subunit [NFL (-/-)] or the overexpression of human NFL [hNFL (+/+)]. Transgenic and wild-type C57bl/6 mice were examined from 1 month to 18 months of age, and the temporal pattern of motor neuron degeneration, microglial and astrocytic proliferation, and heat shock protein-70 (HSP-70) expression characterized. We observed three overlapping phases in both transgenic mice, including transient aggregate formation, reactive microgliosis, and progressive motor neuron loss. However, only NFL (-/-) mice demonstrated significant astrogliosis and HSP-70 upregulation in both motor neurons and astrocytes. These in vivo models suggest that the development of NF aggregates in motor neurons leads to motor neuron death, but that the interaction between the degenerating motor neurons and the adjacent non-neuronal cells may differ significantly depending on the etiology of the NF aggregate itself.

  19. In vivo treatment with interleukin 12 protects mice from immune abnormalities observed during murine acquired immunodeficiency syndrome (MAIDS)

    PubMed Central

    1994-01-01

    Lymphoproliferation, chronic B cell activation resulting in hypergammaglobulinemia, and profound immunodeficiency are prominent features of a retrovirus-induced syndrome designated murine acquired immunodeficiency syndrome (MAIDS). In vivo treatment of infected mice with recombinant interleukin 12 (IL-12) beginning at the time of infection or up to 9 wk after virus inoculation markedly inhibited the development of splenomegaly and lymphadenopathy, as well as B cell activation and Ig secretion. Treatment with IL-12 also had major effects in preventing induction of several immune defects including impaired production of interferon gamma (IFN-gamma) and IL-2 and depressed proliferative responses to various stimuli. The therapeutic effects of IL-12 on the immune system of mice with MAIDS were also associated with reduced expression of the retrovirus that causes this disease (BM5def), with lesser effects on expression of ecotropic MuLV. IL-12 treatment was not effective in IFN-gamma knockout mice or in infected mice treated simultaneously with IL-12 and anti-IFN-gamma. These results demonstrate that induction and progression of MAIDS are antagonized by IL-12 through high-level expression of IFN-gamma and may provide an experimental basis for developing treatments of retrovirus- induced immune disorders with similar immunopathogenic mechanisms. PMID:7964495

  20. Altered Tnnt3 characterizes selective weakness of fast fibers in mice overexpressing FSHD region gene 1 (FRG1)

    PubMed Central

    Sancisi, Valentina; Germinario, Elena; Esposito, Alessandra; Morini, Elisabetta; Peron, Samantha; Moggio, Maurizio; Tomelleri, Giuliano; Danieli-Betto, Daniela

    2013-01-01

    Facioscapulohumeral muscular dystrophy (FSHD), a common hereditary myopathy, is characterized by atrophy and weakness of selective muscle groups. FSHD is considered an autosomal dominant disease with incomplete penetrance and unpredictable variability of clinical expression within families. Mice overexpressing FRG1 (FSHD region gene 1), a candidate gene for this disease, develop a progressive myopathy with features of the human disorder. Here, we show that in FRG1-overexpressing mice, fast muscles, which are the most affected by the dystrophic process, display anomalous fast skeletal troponin T (fTnT) isoform, resulting from the aberrant splicing of the Tnnt3 mRNA that precedes the appearance of dystrophic signs. We determine that muscles of FRG1 mice develop less strength due to impaired contractile properties of fast-twitch fibers associated with an anomalous MyHC-actin ratio and a reduced sensitivity to Ca2+. We demonstrate that the decrease of Ca2+ sensitivity of fast-twitch fibers depends on the anomalous troponin complex and can be rescued by the substitution with the wild-type proteins. Finally, we find that the presence of aberrant splicing isoforms of TNNT3 characterizes dystrophic muscles in FSHD patients. Collectively, our results suggest that anomalous TNNT3 profile correlates with the muscle impairment in both humans and mice. On the basis of these results, we propose that aberrant fTnT represents a biological marker of muscle phenotype severity and disease progression. PMID:24305066

  1. Human Endometrial Side Population Cells Exhibit Genotypic, Phenotypic and Functional Features of Somatic Stem Cells

    PubMed Central

    Cervelló, Irene; Gil-Sanchis, Claudia; Mas, Aymara; Delgado-Rosas, Francisco; Martínez-Conejero, José Antonio; Galán, Amparo; Martínez-Romero, Alicia; Martínez, Sebastian; Navarro, Ismael; Ferro, Jaime; Horcajadas, José Antonio; Esteban, Francisco José; O'Connor, José Enrique; Pellicer, Antonio; Simón, Carlos

    2010-01-01

    During reproductive life, the human endometrium undergoes around 480 cycles of growth, breakdown and regeneration should pregnancy not be achieved. This outstanding regenerative capacity is the basis for women's cycling and its dysfunction may be involved in the etiology of pathological disorders. Therefore, the human endometrial tissue must rely on a remarkable endometrial somatic stem cells (SSC) population. Here we explore the hypothesis that human endometrial side population (SP) cells correspond to somatic stem cells. We isolated, identified and characterized the SP corresponding to the stromal and epithelial compartments using endometrial SP genes signature, immunophenotyping and characteristic telomerase pattern. We analyzed the clonogenic activity of SP cells under hypoxic conditions and the differentiation capacity in vitro to adipogenic and osteogenic lineages. Finally, we demonstrated the functional capability of endometrial SP to develop human endometrium after subcutaneous injection in NOD-SCID mice. Briefly, SP cells of human endometrium from epithelial and stromal compartments display genotypic, phenotypic and functional features of SSC. PMID:20585575

  2. VPAC2 (vasoactive intestinal peptide receptor type 2) receptor deficient mice develop exacerbated experimental autoimmune encephalomyelitis with increased Th1/Th17 and reduced Th2/Treg responses

    PubMed Central

    Wang, Yuqi; Lopez, Robert; Waschek, James

    2014-01-01

    Vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase-activating polypeptide (PACAP) are two structurally-related neuropeptides with widespread expression in the central and peripheral nervous systems. Although these peptides have been repeatedly shown to exert potent anti-inflammatory actions when administered in animal models of inflammatory disease, mice deficient in VIP and PACAP were recently shown to exhibit different phenotypes (ameliorated and exacerbated, respectively) in response to experimental autoimmune encephalomyelitis (EAE). Therefore, elucidating what are the specific immunoregulatory roles played by each of their receptor subtypes (VPAC1, VPAC2, and PAC1) is critical. In this study, we found that mice with a genetic deletion of VIPR2, encoding the VPAC2 receptor, exhibited exacerbated (MOG35-55)-induced EAE compared to wild type mice, characterized by enhanced clinical and histopathological features, increased proinflammatory cytokines (TNF-α, IL-6, IFN-γ (Th1), and IL-17 (Th17)) and reduced anti-inflammatory cytokines (IL-10, TGFβ, and IL-4 (Th2)) in the CNS and lymph nodes. Moreover, the abundance and proliferative index of lymph node, thymus and CNS CD4+CD25+FoxP3+ Tregs were strikingly reduced in VPAC2-deficient mice with EAE. Finally, the in vitro suppressive activity of lymph node and splenic Tregs from VPAC2-deficient mice was impaired. Overall, our results demonstrate critical protective roles for PACAP and the VPAC2 receptor against autoimmunity, promoting the expansion and maintenance of the Treg pool. PMID:25305591

  3. Favorite Demonstrations: A Macroscopic Demonstration of a Microscopic Phenomenon.

    ERIC Educational Resources Information Center

    Mellen, John W.

    1988-01-01

    Finding ways to demonstrate microscopic phenomena and contending with life science students' lack of interest in physical principles are two problems in laboratory courses. Describes a clinical laboratory test for parasite infection that can be used to effectively solve both of them. (RT)

  4. Demonstration Extension: Copper-to-Silver-to-Gold Penny Demonstration

    ERIC Educational Resources Information Center

    Vitz, Ed

    2008-01-01

    This demonstration, if done in the original way, can lead to fires in waste containers (sometimes in the middle of the night after the experiment has been conducted), because pyrophoric zinc is generated by suspending powdered zinc in hot sodium hydroxide. This is avoided by using hot ZnSO[subscript 4].

  5. Tested Demonstrations. Brownian Motion: A Classroom Demonstration and Student Experiment.

    ERIC Educational Resources Information Center

    Kirksey, H. Graden; Jones, Richard F.

    1988-01-01

    Shows how video recordings of the Brownian motion of tiny particles may be made. Describes a classroom demonstration and cites a reported experiment designed to show the random nature of Brownian motion. Suggests a student experiment to discover the distance a tiny particle travels as a function of time. (MVL)

  6. Defective response inhibition and collicular noradrenaline enrichment in mice with duplicated retinotopic map in the superior colliculus.

    PubMed

    Mathis, Chantal; Savier, Elise; Bott, Jean-Bastien; Clesse, Daniel; Bevins, Nicholas; Sage-Ciocca, Dominique; Geiger, Karin; Gillet, Anaïs; Laux-Biehlmann, Alexis; Goumon, Yannick; Lacaud, Adrien; Lelièvre, Vincent; Kelche, Christian; Cassel, Jean-Christophe; Pfrieger, Frank W; Reber, Michael

    2015-01-01

    The superior colliculus is a hub for multisensory integration necessary for visuo-spatial orientation, control of gaze movements and attention. The multiple functions of the superior colliculus have prompted hypotheses about its involvement in neuropsychiatric conditions, but to date, this topic has not been addressed experimentally. We describe experiments on genetically modified mice, the Isl2-EphA3 knock-in line, that show a well-characterized duplication of the retino-collicular and cortico-collicular axonal projections leading to hyperstimulation of the superior colliculus. To explore the functional impact of collicular hyperstimulation, we compared the performance of homozygous knock-in, heterozygous knock-in and wild-type mice in several behavioral tasks requiring collicular activity. The light/dark box test and Go/No-Go conditioning task revealed that homozygous mutant mice exhibit defective response inhibition, a form of impulsivity. This defect was specific to attention as other tests showed no differences in visually driven behavior, motivation, visuo-spatial learning and sensorimotor abilities among the different groups of mice. Monoamine quantification and gene expression profiling demonstrated a specific enrichment of noradrenaline only in the superficial layers of the superior colliculus of Isl2-EphA3 knock-in mice, where the retinotopy is duplicated, whereas transcript levels of receptors, transporters and metabolic enzymes of the monoaminergic pathway were not affected. We demonstrate that the defect in response inhibition is a consequence of noradrenaline imbalance in the superficial layers of the superior colliculus caused by retinotopic map duplication. Our results suggest that structural abnormalities in the superior colliculus can cause defective response inhibition, a key feature of attention-deficit disorders.

  7. Defective response inhibition and collicular noradrenaline enrichment in mice with duplicated retinotopic map in the superior colliculus.

    PubMed

    Mathis, Chantal; Savier, Elise; Bott, Jean-Bastien; Clesse, Daniel; Bevins, Nicholas; Sage-Ciocca, Dominique; Geiger, Karin; Gillet, Anaïs; Laux-Biehlmann, Alexis; Goumon, Yannick; Lacaud, Adrien; Lelièvre, Vincent; Kelche, Christian; Cassel, Jean-Christophe; Pfrieger, Frank W; Reber, Michael

    2015-01-01

    The superior colliculus is a hub for multisensory integration necessary for visuo-spatial orientation, control of gaze movements and attention. The multiple functions of the superior colliculus have prompted hypotheses about its involvement in neuropsychiatric conditions, but to date, this topic has not been addressed experimentally. We describe experiments on genetically modified mice, the Isl2-EphA3 knock-in line, that show a well-characterized duplication of the retino-collicular and cortico-collicular axonal projections leading to hyperstimulation of the superior colliculus. To explore the functional impact of collicular hyperstimulation, we compared the performance of homozygous knock-in, heterozygous knock-in and wild-type mice in several behavioral tasks requiring collicular activity. The light/dark box test and Go/No-Go conditioning task revealed that homozygous mutant mice exhibit defective response inhibition, a form of impulsivity. This defect was specific to attention as other tests showed no differences in visually driven behavior, motivation, visuo-spatial learning and sensorimotor abilities among the different groups of mice. Monoamine quantification and gene expression profiling demonstrated a specific enrichment of noradrenaline only in the superficial layers of the superior colliculus of Isl2-EphA3 knock-in mice, where the retinotopy is duplicated, whereas transcript levels of receptors, transporters and metabolic enzymes of the monoaminergic pathway were not affected. We demonstrate that the defect in response inhibition is a consequence of noradrenaline imbalance in the superficial layers of the superior colliculus caused by retinotopic map duplication. Our results suggest that structural abnormalities in the superior colliculus can cause defective response inhibition, a key feature of attention-deficit disorders. PMID:24647754

  8. Features in visual search combine linearly

    PubMed Central

    Pramod, R. T.; Arun, S. P.

    2014-01-01

    Single features such as line orientation and length are known to guide visual search, but relatively little is known about how multiple features combine in search. To address this question, we investigated how search for targets differing in multiple features (intensity, length, orientation) from the distracters is related to searches for targets differing in each of the individual features. We tested race models (based on reaction times) and co-activation models (based on reciprocal of reaction times) for their ability to predict multiple feature searches. Multiple feature searches were best accounted for by a co-activation model in which feature information combined linearly (r = 0.95). This result agrees with the classic finding that these features are separable i.e., subjective dissimilarity ratings sum linearly. We then replicated the classical finding that the length and width of a rectangle are integral features—in other words, they combine nonlinearly in visual search. However, to our surprise, upon including aspect ratio as an additional feature, length and width combined linearly and this model outperformed all other models. Thus, length and width of a rectangle became separable when considered together with aspect ratio. This finding predicts that searches involving shapes with identical aspect ratio should be more difficult than searches where shapes differ in aspect ratio. We confirmed this prediction on a variety of shapes. We conclude that features in visual search co-activate linearly and demonstrate for the first time that aspect ratio is a novel feature that guides visual search. PMID:24715328

  9. Degeneration of beta-amyloid-associated cholinergic structures in transgenic APP SW mice.

    PubMed

    Lüth, Hans-Joachim; Apelt, Jenny; Ihunwo, Amadi O; Arendt, Thomas; Schliebs, Reinhard

    2003-07-01

    Cholinergic dysfunction is a consistent feature of Alzheimer's disease, and the interrelationship between beta-amyloid deposits, inflammation and early cholinergic cell loss is still not fully understood. To characterize the mechanisms by which beta-amyloid and pro-inflammatory cytokines may exert specific degenerating actions on cholinergic cells ultrastructural investigations by electron microscopy were performed in brain sections from transgenic Tg2576 mice that express the Swedish double mutation of the human amyloid precursor protein and progressively develop beta-amyloid plaques during aging. Both light and electron microscopical investigations of the cerebral cortex of 19-month-old transgenic mice revealed a number of pathological tissue responses in close proximity of beta-amyloid plaques, such as activated microglia, astroglial proliferation, increased number of fibrous astrocytes, brain edema, degeneration of nerve cells, dendrites and axon terminals. Ultrastructural detection of choline acetyl transferase (ChAT)-immunostaining in cerebral cortical sections of transgenic mice clearly demonstrated degeneration of ChAT-immunoreactive fibres in the environment of beta-amyloid plaques and activated glial cells suggesting a role of beta-amyloid and/or inflammation in specific degeneration of cholinergic synaptic structures. PMID:12788508

  10. Behavior and the cholinergic parameters in olfactory bulbectomized female rodents: Difference between rats and mice.

    PubMed

    Stepanichev, Mikhail; Markov, Daniil; Pasikova, Natalia; Gulyaeva, Natalia

    2016-01-15

    Olfactory bulbectomy (OBX) in rodents induces a wide spectrum of functional disturbances, including behavioral, neurochemical, and neuromorphological alterations. We have examined the effects of OBX on behavior and the parameters of the cholinergic system in female rats and mice. In rats, OBX resulted in the appearance of some depressive-like behavioral marks, such as the decreased sucrose consumption, hyperactivity, impaired short-term memory and anxiety-like behavioral features, such as shortened presence in the center of the open field arena or open arms of the elevated plus-maze and an enhancement of avoidance behavior. These behavioral abnormalities could be associated with disturbances in hippocampal function, this suggestion being supported by the presence of cellular changes in this brain structure. No effect of OBX on the number of cholinergic neurons in the medial septum-diagonal band as well as on the acetylcholine content and acetylcholinesterase activity in the septum, hippocampus, and neocortex could be detected. In contrast, in mice, OBX impaired spontaneous alternation behavior and decreased the number of cholinergic neurons in the medial septum-diagonal band. These data demonstrate that rats and mice differently respond to OBX, in particular, OBX does not significantly affect the cholinergic system in rats. PMID:26431763

  11. Behavior and the cholinergic parameters in olfactory bulbectomized female rodents: Difference between rats and mice.

    PubMed

    Stepanichev, Mikhail; Markov, Daniil; Pasikova, Natalia; Gulyaeva, Natalia

    2016-01-15

    Olfactory bulbectomy (OBX) in rodents induces a wide spectrum of functional disturbances, including behavioral, neurochemical, and neuromorphological alterations. We have examined the effects of OBX on behavior and the parameters of the cholinergic system in female rats and mice. In rats, OBX resulted in the appearance of some depressive-like behavioral marks, such as the decreased sucrose consumption, hyperactivity, impaired short-term memory and anxiety-like behavioral features, such as shortened presence in the center of the open field arena or open arms of the elevated plus-maze and an enhancement of avoidance behavior. These behavioral abnormalities could be associated with disturbances in hippocampal function, this suggestion being supported by the presence of cellular changes in this brain structure. No effect of OBX on the number of cholinergic neurons in the medial septum-diagonal band as well as on the acetylcholine content and acetylcholinesterase activity in the septum, hippocampus, and neocortex could be detected. In contrast, in mice, OBX impaired spontaneous alternation behavior and decreased the number of cholinergic neurons in the medial septum-diagonal band. These data demonstrate that rats and mice differently respond to OBX, in particular, OBX does not significantly affect the cholinergic system in rats.

  12. Eliminating microglia in Alzheimer's mice prevents neuronal loss without modulating amyloid-β pathology.

    PubMed

    Spangenberg, Elizabeth E; Lee, Rafael J; Najafi, Allison R; Rice, Rachel A; Elmore, Monica R P; Blurton-Jones, Mathew; West, Brian L; Green, Kim N

    2016-04-01

    In addition to amyloid-β plaque and tau neurofibrillary tangle deposition, neuroinflammation is considered a key feature of Alzheimer's disease pathology. Inflammation in Alzheimer's disease is characterized by the presence of reactive astrocytes and activated microglia surrounding amyloid plaques, implicating their role in disease pathogenesis. Microglia in the healthy adult mouse depend on colony-stimulating factor 1 receptor (CSF1R) signalling for survival, and pharmacological inhibition of this receptor results in rapid elimination of nearly all of the microglia in the central nervous system. In this study, we set out to determine if chronically activated microglia in the Alzheimer's disease brain are also dependent on CSF1R signalling, and if so, how these cells contribute to disease pathogenesis. Ten-month-old 5xfAD mice were treated with a selective CSF1R inhibitor for 1 month, resulting in the elimination of ∼80% of microglia. Chronic microglial elimination does not alter amyloid-β levels or plaque load; however, it does rescue dendritic spine loss and prevent neuronal loss in 5xfAD mice, as well as reduce overall neuroinflammation. Importantly, behavioural testing revealed improvements in contextual memory. Collectively, these results demonstrate that microglia contribute to neuronal loss, as well as memory impairments in 5xfAD mice, but do not mediate or protect from amyloid pathology.

  13. Alcohol Transportation Fuels Demonstration Program

    SciTech Connect

    Kinoshita, C.M.

    1990-01-01

    Hawaii has abundant natural energy resources, especially biomass, that could be used to produce alternative fuels for ground transportation and electricity. This report summarizes activities performed during 1988 to June 1991 in the first phase of the Alcohol Transportation Fuels Demonstration Program. The Alcohol Transportation Fuels Demonstration Program was funded initially by the Energy Division of the State of Hawaii's Department of Business, Economic Development and Tourism, and then by the US Department of Energy. This program was intended to support the transition to an altemative transportation fuel, methanol, by demonstrating the use of methanol fuel and methanol-fueled vehicles, and solving the problems associated with that fuel. Specific objectives include surveying renewable energy resources and ground transportation in Hawaii; installing a model methanol fueling station; demonstrating a methanol-fueled fleet of (spark-ignition engine) vehicles; evaluating modification strategies for methanol-fueled diesel engines and fuel additives; and investigating the transition to methanol fueling. All major objectives of Phase I were met (survey of local renewable resources and ground transportation, installation of methanol refueling station, fleet demonstration, diesel engine modification and additive evaluation, and dissemination of information on alternative fueling), and some specific problems (e.g., relating to methanol fuel contamination during handling and refueling) were identified and solved. Several key issues emerging from Phase I (e.g., methanol corrosion, flame luminosity, and methanol-transition technoeconomics) were recommended as topics for follow-on research in subsequent phases of this program.

  14. Demonstration of Active Combustion Control

    NASA Technical Reports Server (NTRS)

    Lovett, Jeffrey A.; Teerlinck, Karen A.; Cohen, Jeffrey M.

    2008-01-01

    The primary objective of this effort was to demonstrate active control of combustion instabilities in a direct-injection gas turbine combustor that accurately simulates engine operating conditions and reproduces an engine-type instability. This report documents the second phase of a two-phase effort. The first phase involved the analysis of an instability observed in a developmental aeroengine and the design of a single-nozzle test rig to replicate that phenomenon. This was successfully completed in 2001 and is documented in the Phase I report. This second phase was directed toward demonstration of active control strategies to mitigate this instability and thereby demonstrate the viability of active control for aircraft engine combustors. This involved development of high-speed actuator technology, testing and analysis of how the actuation system was integrated with the combustion system, control algorithm development, and demonstration testing in the single-nozzle test rig. A 30 percent reduction in the amplitude of the high-frequency (570 Hz) instability was achieved using actuation systems and control algorithms developed within this effort. Even larger reductions were shown with a low-frequency (270 Hz) instability. This represents a unique achievement in the development and practical demonstration of active combustion control systems for gas turbine applications.

  15. Buried Waste Integrated Demonstration Plan

    SciTech Connect

    Kostelnik, K.M.

    1991-12-01

    This document presents the plan of activities for the Buried Waste Integrated Demonstration (BWID) program which supports the environmental restoration (ER) objectives of the Department of Energy (DOE) Complex. Discussed in this plan are the objectives, organization, roles and responsibilities, and the process for implementing and managing BWID. BWID is hosted at the Idaho National Engineering Laboratory (INEL), but involves participants from throughout the DOE Complex, private industry, universities, and the international community. These participants will support, demonstrate, and evaluate a suite of advanced technologies representing a comprehensive remediation system for the effective and efficient remediation of buried waste. The processes for identifying technological needs, screening candidate technologies for applicability and maturity, selecting appropriate technologies for demonstration, field demonstrating, evaluation of results and transferring technologies to environmental restoration programs are also presented. This document further describes the elements of project planning and control that apply to BWID. It addresses the management processes, operating procedures, programmatic and technical objectives, and schedules. Key functions in support of each demonstration such as regulatory coordination, safety analyses, risk evaluations, facility requirements, and data management are presented.

  16. Status of the Majorana Demonstrator

    SciTech Connect

    Cuesta, C.; Buuck, M.; Detwiler, J. A.; Gruszko, J.; Guinn, I. S.; Leon, J.; Robertson, R. G. H.; Abgrall, N.; Bradley, A. W.; Chan, Y.-D.; Mertens, S.; Poon, A. W. P.; Arnquist, I. J.; Hoppe, E. W.; Kouzes, R. T.; LaFerriere, B. D.; Orrell, J. L.; Avignone, F. T.; Baldenegro-Barrera, C. X.; Bertrand, F. E.; and others

    2015-10-28

    The MAJORANA Collaboration is constructing the MAJORANA DEMONSTRATOR, an ultra-low background, modular, HPGe detector array with a mass of 44-kg (29 kg {sup 76}Ge and 15 kg {sup nat}Ge) to search for neutrinoless double beta decay in {sup 76}Ge. The next generation of tonne-scale Ge-based neutrinoless double beta decay searches will probe the neutrino mass scale in the inverted-hierarchy region. The MAJORANA DEMONSTRATOR is envisioned to demonstrate a path forward to achieve a background rate at or below 1 count/tonne/year in the 4 keV region of interest around the Q-value of 2039 keV. The MAJORANA DEMONSTRATOR follows a modular implementation to be easily scalable to the next generation experiment. First, the prototype module was assembled; it has been continuously taking data from July 2014 to June 2015. Second, Module 1 with more than half of the total enriched detectors and some natural detectors has been assembled and it is being commissioned. Finally, the assembly of Module 2, which will complete MAJORANA DEMONSTRATOR, is already in progress.

  17. Long distance laser communications demonstration

    NASA Astrophysics Data System (ADS)

    Northcott, Malcolm J.; McClaren, A.; Graves, J. E.; Phillips, John; Driver, Don; Abelson, David; Young, David W.; Sluz, Joseph E.; Juarez, Juan C.; Airola, Marc B.; Sova, Raymond M.; Hurt, Harry; Foshee, James

    2007-04-01

    AOptix demonstrated a simulated air-to-air laser communications (laser-com) system over a 147Km distance by establishing a laser communication link between the islands of Hawaii and Maui. We expect the atmospheric conditions encountered during this demonstration to be representative of the worst seeing conditions that could be expected for an actual air to air link. AOptix utilized laser-com terminal incorporating Adaptive Optics (AO) to perform high speed tracking and aberration correction to reduce the effects of the seeing. The demonstration showed the feasibility of establishing high data rate point to point laser-com links between aircraft. In conjunction with Johns Hopkins University Applied Physics Laboratory networking equipment we were able to demonstrate a 40Gbit DWDM link, providing significantly more data throughput than is available using RF technologies. In addition to being very high data rate, the link demonstrates very low beam spread, which gives very high covertness, and a high degree of data security. Since the link is based on 1550nm optical wavelengths it is inherently resistant to jamming.

  18. Histochemical demonstration of methamphetamine by immunocytochemistry.

    PubMed

    Ishiyama, I; Mukaida, M; Yoshii, T; Suyama, H

    1987-05-01

    A method for the demonstration of methamphetamine (MA) by immunocytochemistry was established. The tissues of intoxicated mice, administered various amounts of MA in single doses of from 0.01 to 1 mg of MA-HCl, were fixed in glutaraldehyde-containing fixatives. Cryostat and paraffin slices gave a positive reaction of MA localization by staining the brain, liver, kidney, lung, stomach, spleen, and so forth, with the aid of the indirect immunoperoxidase technique. Those of animals administered a single dose of 0.1 mg or more (over 3 to 4 mg/kg--the usual dose of MA in acute intoxication death in forensic medicine), in particular, gave a strong strong reaction, so that the diagnosis of MA intoxication can be performed by macroscopic observation of stained slices. The histochemical diagnosis of MA intoxication in clinical toxicology and pathology might be regarded as a useful tool, especially in forensic pathology. The following cells gave a strong positive reaction: nerve cells and myelin sheaths, hepatocytes, epithelial cells of the distal part of the renal tubule and of the collecting tubule, alveolar and bronchial epithelial cells of the lung, chief and parietal cells of the gastric gland, capillaries of the renal glomerulus, macrophages in the blood and tissues, and striated muscle cells including cardiocytes. The morphological evidence of the pharmacodynamics and pharmacokinetics of MA can be determined at the cellular level by immunocytochemistry.

  19. The selective advantage of crypsis in mice.

    PubMed

    Vignieri, Sacha N; Larson, Joanna G; Hoekstra, Hopi E

    2010-07-01

    The light color of mice that inhabit the sandy dunes of Florida's coast have served as a textbook example of adaptation for nearly a century, despite the fact that the selective advantage of crypsis has never been directly tested or quantified in nature. Using plasticine mouse models of light and dark color, we demonstrate a strong selective advantage for mice that match their local background substrate. Further our data suggest that stabilizing selection maintains color matching within a single habitat, as models that are both lighter and darker than their local environment are selected against. These results provide empirical evidence in support of the hypothesis that visual hunting predators shape color patterning in Peromyscus mice and suggest a mechanism by which selection drives the pronounced color variation among populations. PMID:20163447

  20. Intrinsic Feature Motion Tracking

    SciTech Connect

    Goddard, Jr., James S.

    2013-03-19

    Subject motion during 3D medical scanning can cause blurring and artifacts in the 3D images resulting in either rescans or poor diagnosis. Anesthesia or physical restraints may be used to eliminate motion but are undesirable and can affect results. This software measures the six degree of freedom 3D motion of the subject during the scan under a rigidity assumption using only the intrinsic features present on the subject area being monitored. This movement over time can then be used to correct the scan data removing the blur and artifacts. The software acquires images from external cameras or images stored on disk for processing. The images are from two or three calibrated cameras in a stereo arrangement. Algorithms extract and track the features over time and calculate position and orientation changes relative to an initial position. Output is the 3D position and orientation change measured at each image.