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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. Mast cells can promote the development of multiple features of chronic asthma in mice

    PubMed Central

    Yu, Mang; Tsai, Mindy; Tam, See-Ying; Jones, Carol; Zehnder, James; Galli, Stephen J.

    2006-01-01

    Bronchial asthma, the most prevalent cause of significant respiratory morbidity in the developed world, typically is a chronic disorder associated with long-term changes in the airways. We developed a mouse model of chronic asthma that results in markedly increased numbers of airway mast cells, enhanced airway responses to methacholine or antigen, chronic inflammation including infiltration with eosinophils and lymphocytes, airway epithelial goblet cell hyperplasia, enhanced expression of the mucin genes Muc5ac and Muc5b, and increased levels of lung collagen. Using mast cell–deficient (KitW-sh/W-sh and/or KitW/W-v) mice engrafted with FcRγ+/+ or FcRγ–/– mast cells, we found that mast cells were required for the full development of each of these features of the model. However, some features also were expressed, although usually at less than wild-type levels, in mice whose mast cells lacked FcRγ and therefore could not be activated by either antigen- and IgE-dependent aggregation of FcεRI or the binding of antigen-IgG1 immune complexes to FcγRIII. These findings demonstrate that mast cells can contribute to the development of multiple features of chronic asthma in mice and identify both FcRγ-dependent and FcRγ-independent pathways of mast cell activation as important for the expression of key features of this asthma model. PMID:16710480

  7. 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

  8. Oxytocin knockout mice demonstrate enhanced intake of sweet and nonsweet carbohydrate solutions.

    PubMed

    Sclafani, Anthony; Rinaman, Linda; Vollmer, Regis R; Amico, Janet A

    2007-05-01

    Oxytocin knockout (OT KO) mice display enhanced intake of nutritive and nonnutritive sweet solutions (i.e., sucrose and saccharin) compared with wild-type (WT) mice of the same C57BL/6 background strain. The present study further investigated the differential behavioral response of OT KO and WT mice to sucrose solutions and also examined intake preferences of OT KO and WT mice for palatable but nonsweet isocaloric solutions of carbohydrate and fat. A progressive ratio operant licking procedure demonstrated that OT KO and WT mice display a similar motivational drive to consume 10% sucrose. A series of two-bottle intake tests revealed that OT KO mice consume significantly larger amounts of both sweet and nonsweet carbohydrate solutions (i.e., sucrose, Polycose, and cornstarch) compared with WT cohorts. Intake pattern analyses revealed that OT KO mice overconsume carbohydrate solutions by initiating more drinking bouts compared with WT mice; bout sizes did not differ between the genotypes. In contrast, OT KO and WT mice did not differ in their intake of Intralipid, a palatable soybean oil emulsion. These findings indicate that the absence of OT in mice does not affect their appetitive drive to consume palatable sucrose solutions. Instead, the absence of OT may increase daily intake of palatable sweet and nonsweet solutions of carbohydrate (but not fat) by selectively blunting or masking processes that contribute to postingestive satiety. PMID:17272659

  9. Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice

    PubMed Central

    Burke, Suzanne D.; Dong, Hongmei; Hazan, Aleah D.; Croy, B. Anne

    2010-01-01

    Objective Pregnancies in diabetic women are at 4–12 more risk for pre-eclampsia, an urgent, acute onset complication of mid to late gestation, than pregnancies in normal women. Hallmarks of pre-eclampsia are hypertension, proteinuria and incomplete modification of endometrial spiral arteries. Transient, pro-angiogenic lymphocytes called uterine Natural Killer (uNK) cells are implicated in human and rodent spiral artery modification. We studied mid to late gestations in spontaneously type 1 diabetic NOD mice to ask if diabetes alters uNK cell homing and/or function. Research design and method Normoglycemic, prediabetic and diabetic NOD mice and controls were mated. Lymphocytes and endometrial endothelium and decidua were studied histologically and in functional assays. Results Conception accelerated progression to overt diabetes in NOD females who had limited spiral artery development, heavier placentae and lighter fetuses displaying numerous birth defects compared with controls. UNK cell numbers were reduced in the decidua basalis of diabetic females while interferon-γ production was elevated. In diabetic NOD mice, decidual expression of the endothelial cell addressin MAdCAM-1 was aberrant in position while VCAM-1 expression was reduced. Assays of lymphocyte adhesion to tissue sections under shear forces indicated that diabetes compromises the potential homing functions of both endometrial endothelium and peripheral NK cells. Conclusions In diabetes, gestational endometrium has immune and vascular defects that likely to contribute to murine fetal loss and birth defects. Analogous problems and pre-eclampsia in diabetic women may involve similar mechanisms. PMID:17827401

  10. 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

  11. Leptin deficiency recapitulates the histological features of pulmonary arterial hypertension in mice

    PubMed Central

    Aytekin, Metin; Tonelli, Adriano R; Farver, Carol F; Feldstein, Ariel E; Dweik, Raed A

    2014-01-01

    Leptin is a neuroendocrine peptide released by adipose tissue that enhances metabolism and acts on the hypothalamus to suppress appetite. Leptin also regulates aspects of cardiovascular function and low serum leptin has been associated with increased mortality in humans. We hypothesized that leptin deficiency alters the structure and function of the pulmonary vasculature. Methods: We examined two groups of C57BL/6 male mice aged 12 weeks: five ob/ob (B6.VLepob/ob) leptin-deficient and five wild type (WT) (C57BL/6) control mice. As expected, weight was significantly greater in ob/ob mice relative to WT mice [weight (g), Mean ± SD): ob/ob 52 ± 2.5 g, wild type 30 ± 2.5 g; p < 0.001]. The pulmonary vasculature of ob/ob mice and WT control animals was examined by histology, immunohistochemistry and immunofluorescence staining. Results: Pulmonary arterial wall thickness was significantly increased in ob/ob mice relative to WT littermates [median (interquartile range) distance in pixels: ob/ob 0.13 (0.05-0.18), wild type 0.03 (0.02-0.04); p = 0.001]. The ob/ob mice also exhibited significant right ventricular hypertrophy in comparison to control animals [RV thickness (Mean ± SD): ob/ob 0.75 ± 0.19, wild type; 0.58 ± 0.13 p < 0.001]. We observed substantial macrophage infiltration and abundant proliferation of myofibroblasts and fibroblasts in histological sections of pulmonary arterioles of ob/ob mice. In addition, we noted increased hyaluronan deposition, colocalizing with SMC-actin in the pulmonary vasculature of ob/ob mice relative to WT controls. Conclusions: The pulmonary pathology of leptin deficiency in ob/ob mice recapitulates many of the histological features of pulmonary vascular diseases, including pulmonary hypertension, suggesting that leptin deficiency is associated to the pathogenesis of pulmonary vascular disease. PMID:24966903

  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. PMID:27207790

  13. 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.

  14. Touchscreen tasks in mice to demonstrate differences between hippocampal and striatal functions.

    PubMed

    Delotterie, David F; Mathis, Chantal; Cassel, Jean-Christophe; Rosenbrock, Holger; Dorner-Ciossek, Cornelia; Marti, Anelise

    2015-04-01

    In mammals, hippocampal and striatal regions are engaged in separable cognitive processes usually assessed through species-specific paradigms. To reconcile cognitive testing among species, translational advantages of the touchscreen-based automated method have been recently promoted. However, it remains undetermined whether similar neural substrates would be involved in such behavioral tasks both in humans and rodents. To address this question, the effects of hippocampal or dorso-striatal fiber-sparing lesions were first assessed in mice through a battery of tasks (experiment A) comprising the acquisition of two touchscreen paradigms, the Paired Associates Learning (dPAL) and Visuo-Motor Conditional Learning (VMCL) tasks, and a more classical T-maze alternation task. Additionally, we sought to determine whether post-acquisition hippocampal lesions would alter memory retrieval in the dPAL task (experiment B). Pre-training lesions of dorsal striatum caused major impairments in all paradigms. In contrast, pre-training hippocampal lesions disrupted the performance of animals trained in the T-maze assay, but spared the acquisition in touchscreen tasks. Nonetheless, post-training hippocampal lesions severely impacted the recall of the previously learned dPAL task. Altogether, our data show that, after having demonstrated their potential in genetically modified mice, touchscreens also reveal perfectly adapted to taxing functional implications of brain structures in mice by means of lesion approaches. Unlike its human counterpart requiring an intact hippocampus, the acquisition of the dPAL task requires the integrity of the dorsal striatum in mice. The hippocampus only later intervenes, when acquired information needs to be retrieved. Touchscreen assays may therefore be suited to study striatal- or hippocampal-dependent forms of learnings in mice. PMID:25687692

  15. [In vitro demonstration of histamine biosynthesis from carnosine by kidneys of pregnant mice].

    PubMed

    Arnould, J M

    1987-01-01

    Kidneys of pregnant mice synthesize histamine when incubated in the presence of carnosine, manganese, and pyridoxal phosphate. Intensity of biosynthesis increases linearly with the amount of enzyme and the incubation time. The reaction can only be catalysed by two enzymes that are located in kidneys and act in succession: carnosinase, which hydrolyzes carnosine into its two moieties, and histidine decarboxylase, which transforms histidine, a product of carnosine degradation, into histamine. The biosynthesis of histamine from carnosine seems to increase with the progress of pregnancy. In nonpregnant mice, kidneys do not effect this biosynthesis. The above results directly demonstrate that carnosine may be used for histamine synthesis when the activity of histidine decarboxylase is high, as in pregnant mouse kidney. Vertebrate carnosine, its role still enigmatic, might thus be mainly a potential histidine reservoir that would be mobilized any time there is a significant requirement for histidine, such as for histamine biosynthesis. PMID:3567723

  16. 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

  17. Connexin26 expression in brain parenchymal cells demonstrated by targeted connexin ablation in transgenic mice.

    PubMed

    Nagy, J I; Lynn, B D; Tress, O; Willecke, K; Rash, J E

    2011-07-01

    Astrocytes are known to express the gap junction forming proteins connexin30 (Cx30) and connexin43 (Cx43), but it has remained controversial whether these cells also express connexin26 (Cx26). To investigate this issue further, we examined immunofluorescence labelling of glial connexins in wild-type vs. transgenic mice with targeted deletion of Cx26 in neuronal and glial cells (Cx26fl/fl:Nestin-Cre mice). The Cx26 antibodies utilized specifically recognized Cx26 and lacked cross reaction with highly homologous Cx30, as demonstrated by immunoblotting and immunofluorescence in Cx26-transfected and Cx30-transfected C6 glioma cells. Punctate immunolabelling of Cx26 with these antibodies was observed in leptomeninges and subcortical brain regions. This labelling was absent in subcortical areas of Cx26fl/fl:Nestin-Cre mice, but persisted in leptomeningeal tissues of these mice, thereby distinguishing localization of Cx26 between parenchymal and non-parenchymal tissue. In subcortical brain parenchyma, Cx26-positive puncta were often co-localized with astrocytic Cx43, and some were localized along astrocyte cell bodies and processes immunolabelled for glial fibrillary acidic protein. Cx26-positive puncta were also co-localized with punctate labelling of Cx47 around oligodendrocyte somata. Comparisons of Cx26 labelling in rodent species revealed a lower density of Cx26-positive puncta and a more restricted distribution in subcortical regions of mouse compared with rat brain, perhaps partly explaining reported difficulties in detection of Cx26 in mouse brain parenchyma using antibodies or Cx26 gene reporters. These results support our earlier observations of Cx26 expression in astrocytes and its ultrastructural localization in individual gap junction plaques formed between astrocytes as well as in heterotypic gap junctions between astrocytes and oligodendrocytes. PMID:21714813

  18. Rabies virus infection of primary neuronal cultures and adult mice: failure to demonstrate evidence of excitotoxicity.

    PubMed

    Weli, Simon C; Scott, Courtney A; Ward, Christopher A; Jackson, Alan C

    2006-10-01

    Cultures derived from the cerebral cortices and hippocampi of 17-day-old mouse fetuses infected with the CVS strain of rabies virus showed loss of trypan blue exclusion, morphological apoptotic features, and activated caspase 3 expression, indicating apoptosis. The NMDA (N-methyl-D-aspartate acid) antagonists ketamine (125 microM) and MK-801 (60 microM) were found to have no significant neuroprotective effect on CVS-infected neurons, while the caspase inhibitor Ac-Asp-Glu-Val aspartic acid aldehyde (25 microM) exerted a marked neuroprotective effect. Glutamate-stimulated increases in levels of intracellular calcium were reduced in CVS-infected hippocampal neurons. Ketamine (120 mg/kg of body weight/day intraperitoneally) given to CVS-infected adult mice produced no beneficial effects. We have found no supportive evidence that excitotoxicity plays an important role in rabies virus infection. PMID:17005706

  19. Diacylglycerol Lipase α Knockout Mice Demonstrate Metabolic and Behavioral Phenotypes Similar to Those of Cannabinoid Receptor 1 Knockout Mice

    PubMed Central

    Powell, David R.; Gay, Jason P.; Wilganowski, Nathaniel; Doree, Deon; Savelieva, Katerina V.; Lanthorn, Thomas H.; Read, Robert; Vogel, Peter; Hansen, Gwenn M.; Brommage, Robert; Ding, Zhi-Ming; Desai, Urvi; Zambrowicz, Brian

    2015-01-01

    After creating >4,650 knockouts (KOs) of independent mouse genes, we screened them by high-throughput phenotyping and found that cannabinoid receptor 1 (Cnr1) KO mice had the same lean phenotype published by others. We asked if our KOs of DAG lipase α or β (Dagla or Daglb), which catalyze biosynthesis of the endocannabinoid (EC) 2-arachidonoylglycerol (2-AG), or Napepld, which catalyzes biosynthesis of the EC anandamide, shared the lean phenotype of Cnr1 KO mice. We found that Dagla KO mice, but not Daglb or Napepld KO mice, were among the leanest of 3651 chow-fed KO lines screened. In confirmatory studies, chow- or high fat diet-fed Dagla and Cnr1 KO mice were leaner than wild-type (WT) littermates; when data from multiple cohorts of adult mice were combined, body fat was 47 and 45% lower in Dagla and Cnr1 KO mice, respectively, relative to WT values. By contrast, neither Daglb nor Napepld KO mice were lean. Weanling Dagla KO mice ate less than WT mice and had body weight (BW) similar to pair-fed WT mice, and adult Dagla KO mice had normal activity and VO2 levels, similar to Cnr1 KO mice. Our Dagla and Cnr1 KO mice also had low fasting insulin, triglyceride, and total cholesterol levels, and after glucose challenge had normal glucose but very low insulin levels. Dagla and Cnr1 KO mice also showed similar responses to a battery of behavioral tests. These data suggest: (1) the lean phenotype of young Dagla and Cnr1 KO mice is mainly due to hypophagia; (2) in pathways where ECs signal through Cnr1 to regulate food intake and other metabolic and behavioral phenotypes observed in Cnr1 KO mice, Dagla alone provides the 2-AG that serves as the EC signal; and (3) small molecule Dagla inhibitors with a pharmacokinetic profile similar to that of Cnr1 inverse agonists are likely to mirror the ability of these Cnr1 inverse agonists to lower BW and improve glycemic control in obese patients with type 2 diabetes, but may also induce undesirable neuropsychiatric side

  20. Diacylglycerol Lipase α Knockout Mice Demonstrate Metabolic and Behavioral Phenotypes Similar to Those of Cannabinoid Receptor 1 Knockout Mice.

    PubMed

    Powell, David R; Gay, Jason P; Wilganowski, Nathaniel; Doree, Deon; Savelieva, Katerina V; Lanthorn, Thomas H; Read, Robert; Vogel, Peter; Hansen, Gwenn M; Brommage, Robert; Ding, Zhi-Ming; Desai, Urvi; Zambrowicz, Brian

    2015-01-01

    After creating >4,650 knockouts (KOs) of independent mouse genes, we screened them by high-throughput phenotyping and found that cannabinoid receptor 1 (Cnr1) KO mice had the same lean phenotype published by others. We asked if our KOs of DAG lipase α or β (Dagla or Daglb), which catalyze biosynthesis of the endocannabinoid (EC) 2-arachidonoylglycerol (2-AG), or Napepld, which catalyzes biosynthesis of the EC anandamide, shared the lean phenotype of Cnr1 KO mice. We found that Dagla KO mice, but not Daglb or Napepld KO mice, were among the leanest of 3651 chow-fed KO lines screened. In confirmatory studies, chow- or high fat diet-fed Dagla and Cnr1 KO mice were leaner than wild-type (WT) littermates; when data from multiple cohorts of adult mice were combined, body fat was 47 and 45% lower in Dagla and Cnr1 KO mice, respectively, relative to WT values. By contrast, neither Daglb nor Napepld KO mice were lean. Weanling Dagla KO mice ate less than WT mice and had body weight (BW) similar to pair-fed WT mice, and adult Dagla KO mice had normal activity and VO2 levels, similar to Cnr1 KO mice. Our Dagla and Cnr1 KO mice also had low fasting insulin, triglyceride, and total cholesterol levels, and after glucose challenge had normal glucose but very low insulin levels. Dagla and Cnr1 KO mice also showed similar responses to a battery of behavioral tests. These data suggest: (1) the lean phenotype of young Dagla and Cnr1 KO mice is mainly due to hypophagia; (2) in pathways where ECs signal through Cnr1 to regulate food intake and other metabolic and behavioral phenotypes observed in Cnr1 KO mice, Dagla alone provides the 2-AG that serves as the EC signal; and (3) small molecule Dagla inhibitors with a pharmacokinetic profile similar to that of Cnr1 inverse agonists are likely to mirror the ability of these Cnr1 inverse agonists to lower BW and improve glycemic control in obese patients with type 2 diabetes, but may also induce undesirable neuropsychiatric side

  1. 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…

  2. Arrhythmia and cardiac defects are a feature of spinal muscular atrophy model mice

    PubMed Central

    Heier, Christopher R.; Satta, Rosalba; Lutz, Cathleen; DiDonato, Christine J.

    2010-01-01

    Proximal spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality. Traditionally, SMA has been described as a motor neuron disease; however, there is a growing body of evidence that arrhythmia and/or cardiomyopathy may present in SMA patients at an increased frequency. Here, we ask whether SMA model mice possess such phenotypes. We find SMA mice suffer from severe bradyarrhythmia characterized by progressive heart block and impaired ventricular depolarization. Echocardiography further confirms functional cardiac deficits in SMA mice. Additional investigations show evidence of both sympathetic innervation defects and dilated cardiomyopathy at late stages of disease. Based upon these data, we propose a model in which decreased sympathetic innervation causes autonomic imbalance. Such imbalance would be characterized by a relative increase in the level of vagal tone controlling heart rate, which is consistent with bradyarrhythmia and progressive heart block. Finally, treatment with the histone deacetylase inhibitor trichostatin A, a drug known to benefit phenotypes of SMA model mice, produces prolonged maturation of the SMA heartbeat and an increase in cardiac size. Treated mice maintain measures of motor function throughout extended survival though they ultimately reach death endpoints in association with a progression of bradyarrhythmia. These data represent the novel identification of cardiac arrhythmia as an early and progressive feature of murine SMA while providing several new, quantitative indices of mouse health. Together with clinical cases that report similar symptoms, this reveals a new area of investigation that will be important to address as we move SMA therapeutics towards clinical success. PMID:20693262

  3. 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

  4. 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

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

    PubMed

    Oestereich, Lisa; Lüdtke, Anja; Ruibal, Paula; Pallasch, Elisa; Kerber, Romy; Rieger, Toni; Wurr, Stephanie; Bockholt, Sabrina; Pérez-Girón, José V; Krasemann, Susanne; Günther, Stephan; Muñoz-Fontela, César

    2016-05-01

    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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Functional MRI demonstrates pain perception in hand osteoarthritis has features of central pain processing

    PubMed Central

    Sofat, Nidhi; Smee, Cori; Hermansson, Monika; Howard, Matthew; Baker, Emma H; Howe, Franklyn A; Barrick, Thomas R

    2013-01-01

    Background Hand osteoarthritis (HOA) is typified by pain and reduced function. We hypothesised that people with HOA have enhanced sensitivity and activation of peripheral nociceptors in the hand, thereby potentiating chronic pain. In our study we aimed to assess if central sensitisation mediates pain perception in osteoarthritis of the hand. Methods Participants with proximal and distal interphalangeal joint (PIP/DIP) HOA and non-OA controls were recruited. Clinical pain scores using the visual analogue scale (VAS) were recorded before and after performing a painful hand task. Central pain processing was evaluated with functional brain neuroimaging (fMRI) using a finger flexion-extension (FFE) task performed over 3 minutes. Data was analysed with FMRIB software (www.fmrib.ox.ac.uk/fsl). Group mean activation of functional MRI signal between hand osteoarthritis and control non-arthritic participants was compared. Results Our group of hand OA participants reported high pain levels compared with non-arthritic controls as demonstrated by the mean VAS in hand OA participants of 59.31± 8.19 mm compared to 4.00 ± 1.89 mm in controls (p < 0.0001), despite all participants reporting analgesic use. Functional MRI analysis showed increased activation in the thalamus, cingulate, frontal and somatosensory cortex in the hand OA group but not in controls (thresholded at p < 0.05). Regions of activation were mapped to Brodmann areas 3, 4, 6, 9, 13, 22, 24 and 44. Activated regions found in our study are recognised higher brain pain processing centres implicated in central sensitisation. Conclusions People with hand osteoarthritis demonstrated features of central sensitisation that was evident after a finger flexion-extension task using functional MRI. Functional MRI is a useful biomarker in detecting pain in hand osteoarthritis and could be used in future hand osteoarthritis pain studies to evaluate pain modulation strategies. PMID:24294351

  13. 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

  14. Ceruloplasmin/Hephaestin Knockout Mice Model Morphologic and Molecular Features of AMD

    PubMed Central

    Hadziahmetovic, Majda; Dentchev, Tzvete; Song, Ying; Haddad, Nadine; He, Xining; Hahn, Paul; Pratico, Domenico; Wen, Rong; Harris, Z. Leah; Lambris, John D.; Beard, John; Dunaief, Joshua L.

    2008-01-01

    Purpose Iron is an essential element in human metabolism but also is a potent generator of oxidative damage with levels that increase with age. Several studies suggest that iron accumulation may be a factor in age-related macular degeneration (AMD). In prior studies, both iron overload and features of AMD were identified in mice deficient in the ferroxidase ceruloplasmin (Cp) and its homologue hephaestin (Heph) (double knockout, DKO). In this study, the location and timing of iron accumulation, the rate and reproducibility of retinal degeneration, and the roles of oxidative stress and complement activation were determined. Methods Morphologic analysis and histochemical iron detection by Perls' staining was performed on retina sections from DKO and control mice. Immunofluorescence and immunohistochemistry were performed with antibodies detecting activated complement factor C3, transferrin receptor, L-ferritin, and macrophages. Tissue iron levels were measured by atomic absorption spectrophotometry. Isoprostane F2α-VI, a specific marker of oxidative stress, was quantified in the tissue by gas chromatography/mass spectrometry. Results DKOs exhibited highly reproducible age-dependent iron overload, which plateaued at 6 months of age, with subsequent progressive retinal degeneration continuing to at least 12 months. The degeneration shared some features of AMD, including RPE hypertrophy and hyperplasia, photoreceptor degeneration, subretinal neovascularization, RPE lipofuscin accumulation, oxidative stress, and complement activation. Conclusions DKOs have age-dependent iron accumulation followed by retinal degeneration modeling some of the morphologic and molecular features of AMD. Therefore, these mice are a good platform on which to test therapeutic agents for AMD, such as antioxidants, iron chelators, and antiangiogenic agents. PMID:18326691

  15. Histopathologic features of T-cell mediated colonic injury induced with 2,4-dinitrofluorobenzene in BALB/c mice.

    PubMed

    Anić, B; Brkić, T; Banić, M; Heinzl, R; Dohoczky, C; Smud, D; Rotkvić, I; Buljevac, M

    1997-01-01

    The aim of the study was to reveal the histopathologic features of intestinal inflammation as demonstrated in BALB/c mice, using the challenge of 2,4-dinitrofluorobenzene (DNFB) with or without previous sensitization. Forty mice were randomized into 5 groups. Two groups of animals were treated with rectal enema of 0.2% or 1.0% of 2,4-dinitrofluorobenzene solution. Third group was pretreated with 2 sensitizing doses of DNFB. Two control groups were treated with PBS or acetone and vehicle enema only (acetone and olive oil). In order to assess the extent of colonic inflammation and damage, a histopathologic score scale was developed. In contrast to scanty superficial ulcerations and mild edema observed in the control group of animals, edema, ulcerations, hemorrhage, necrosis and infiltration of inflammatory cells were observed in experiment groups treated with enema of DNFB. Total score of lesion as well almost all inflammatory parameters of injury observed were highest in previously sensitized animals. The results of this study clearly demonstrated the pattern of colonic inflammation induced with DNFB using the histopathologic scoring scale system. PMID:9115097

  16. 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…

  17. 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

    2014-01-01

    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. PMID:24832598

  18. 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. PMID:26122048

  19. Cfh Genotype Interacts With Dietary Glycemic Index to Modulate Age-Related Macular Degeneration-Like Features in Mice

    PubMed Central

    Rowan, Sheldon; Weikel, Karen; Chang, Min-Lee; Nagel, Barbara A.; Thinschmidt, Jeffrey S.; Carey, Amanda; Grant, Maria B.; Fliesler, Steven J.; Smith, Donald; Taylor, Allen

    2014-01-01

    Purpose. Age-related macular degeneration (AMD) is a leading cause of visual impairment worldwide. Genetics and diet contribute to the relative risk for developing AMD, but their interactions are poorly understood. Genetic variations in Complement Factor H (CFH), and dietary glycemic index (GI) are major risk factors for AMD. We explored the effects of GI on development of early AMD-like features and changes to central nervous system (CNS) inflammation in Cfh-null mice. Methods. Aged 11-week-old wild type (WT) C57Bl/6J or Cfh-null mice were group pair-fed high or low GI diets for 33 weeks. At 10 months of age, mice were evaluated for early AMD-like features in the neural retina and RPE by light and electron microscopy. Brains were analyzed for Iba1 macrophage/microglia immunostaining, an indicator of inflammation. Results. The 10-month-old WT mice showed no retinal abnormalities on either diet. The Cfh-null mice, however, showed distinct early AMD-like features in the RPE when fed a low GI diet, including vacuolation, disruption of basal infoldings, and increased basal laminar deposits. The Cfh-null mice also showed thinning of the RPE, hypopigmentation, and increased numbers of Iba1-expressing macrophages in the brain, irrespective of diet. Conclusions. The presence of early AMD-like features by 10 months of age in Cfh-null mice fed a low GI diet is surprising, given the apparent protection from the development of such features in aged WT mice or humans consuming lower GI diets. Our findings highlight the need to consider gene–diet interactions when developing animal models and therapeutic approaches to treat AMD. PMID:24370827

  20. Fibroblast growth factor 21-deficient mice demonstrate impaired adaptation to ketosis.

    PubMed

    Badman, Michael K; Koester, Anja; Flier, Jeffrey S; Kharitonenkov, Alexei; Maratos-Flier, Eleftheria

    2009-11-01

    Fibroblast growth factor 21 (FGF21) is a key metabolic regulator. Expressed primarily in liver and adipose tissue, FGF21 is induced via peroxisome proliferator-activated receptor (PPAR) pathways during states requiring increased fatty acid oxidation including fasting and consumption of a ketogenic diet. To test the hypothesis that FGF21 is a physiological regulator that plays a role in lipid oxidation, we generated mice with targeted disruption of the Fgf21 locus (FGF21 knockout). Mice lacking FGF21 had mild weight gain and slightly impaired glucose homeostasis, indicating a role in long-term energy homeostasis. Furthermore, FGF21KO mice tolerated a 24-h fast, indicating that FGF21 is not essential in the early stages of starvation. In contrast to wild-type animals in which feeding KD leads to dramatic weight loss, FGF21KO mice fed KD gained weight, developed hepatosteatosis, and showed marked impairments in ketogenesis and glucose control. This confirms the physiological importance of FGF21 in the adaptation to KD feeding. At a molecular level, these effects were accompanied by lower levels of expression of PGC1alpha and PGC1beta in FGF21KO mice, strongly implicating these key transcriptional regulators in the action of FGF21. Furthermore, within the liver, the maturation of the lipogenic transcription factor sterol regulatory element-binding protein-1c was increased in FGF21KO mice, implicating posttranscriptional events in the maladaptation of FGF21KO mice to KD. These data reinforce the role of FGF21 is a critical regulator of long-term energy balance and metabolism. Mice lacking FGF21 cannot respond appropriately to a ketogenic diet, resulting in an impaired ability to mobilize and utilize lipids. PMID:19819944

  1. Mice Lacking Inducible Nitric Oxide Synthase Demonstrate Impaired Killing of Porphyromonas gingivalis

    PubMed Central

    Gyurko, Robert; Boustany, Gabriel; Huang, Paul L.; Kantarci, Alpdogan; Van Dyke, Thomas E.; Genco, Caroline A.; Gibson III, Frank C.

    2003-01-01

    Porphyromonas gingivalis is a primary etiological agent of generalized severe periodontitis, and emerging data suggest the importance of reactive oxygen and nitrogen species in periodontal tissue damage, as well as in microbial killing. Since nitric oxide (NO) released from inducible NO synthase (iNOS) has been shown to possess immunomodulatory, cytotoxic, and antibacterial effects in experimental models, we challenged iNOS-deficient (iNOS−/−) mice with P. gingivalis by using a subcutaneous chamber model to study the specific contribution of NO to host defense during P. gingivalis infection. iNOS−/− mice inoculated with P. gingivalis developed skin lesions and chamber rejection with higher frequency and to a greater degree than similarly challenged C57BL/6 wild-type (WT) mice. Chamber fluid from iNOS−/− mice possessed significantly more P. gingivalis than that of WT mice. The immunoglobulin G responses to P. gingivalis in serum was similar in WT and iNOS−/− mice, and the inductions of tumor necrosis factor alpha, interleukin-1β and interleukin-6, and prostaglandin E2 were comparable between the two mouse strains. Although no differences in total leukocyte counts in chamber fluids were observed between iNOS−/− and WT mice, the percentage of dead polymorphonuclear leukocytes (PMNs) was significantly greater in iNOS−/− mouse chamber fluids than that of WT samples. Interestingly, casein-elicited PMNs from iNOS−/− mice released more superoxide than did WT PMNs when stimulated with P. gingivalis. These results indicate that modulation of superoxide levels is a mechanism by which NO influences PMN function and that NO is an important element of the host defense against P. gingivalis. PMID:12933833

  2. 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

  3. 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

  4. Software defined networking (SDN) over space division multiplexing (SDM) optical networks: features, benefits and experimental demonstration.

    PubMed

    Amaya, N; Yan, S; Channegowda, M; Rofoee, B R; Shu, Y; Rashidi, M; Ou, Y; Hugues-Salas, E; Zervas, G; Nejabati, R; Simeonidou, D; Puttnam, B J; Klaus, W; Sakaguchi, J; Miyazawa, T; Awaji, Y; Harai, H; Wada, N

    2014-02-10

    We present results from the first demonstration of a fully integrated SDN-controlled bandwidth-flexible and programmable SDM optical network utilizing sliceable self-homodyne spatial superchannels to support dynamic bandwidth and QoT provisioning, infrastructure slicing and isolation. Results show that SDN is a suitable control plane solution for the high-capacity flexible SDM network. It is able to provision end-to-end bandwidth and QoT requests according to user requirements, considering the unique characteristics of the underlying SDM infrastructure. PMID:24663655

  5. 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

  6. Innovative Structural Design Features for a 10 m Solar Sail Demonstrator

    NASA Technical Reports Server (NTRS)

    Laue, G.; Moore, J.; Clayton, W.

    2004-01-01

    The successful development of sail architectures will require careful attention to a number of key issues including but not limited to material strength issues, stress conditions for the membrane, load interactions between membrane and structure, and membrane material planarity. Along with the inherent challenges of fabricating and handling very large membrane structures these issues will pose real challenges for the near-term development of practical sail technologies. SRS has developed innovative technologies that deal directly with the challenges of developing very large sail membranes. Some of these technologies include edge reinforcements and innovative reinforcement attachment techniques, production of flight durable sail materials of less than 2.5 micron thicknesses and large scale fabrication techniques. SRS has employed these technologies in several large 10 m demonstrators that have been delivered to LaRC for solar vacuum testing. Details of the design of this system will be discussed.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. [Virus demonstration and pathologic changes in different phases of coxsackievirus B myocarditis in mice].

    PubMed

    Rabausch-Starz, I; Neu, N; Müller-Hermelink, H K

    1990-01-01

    A/J mice between 15 days and 10 weeks of age were infected intraperitoneally with Coxsackievirus B3 (CVB3). To search for virus in the myocardium various methods were applied: virus isolation from the myocardium, RNA extraction for dot blot hybridization and in situ hybridization. Two different RNA probes, one specific for CVB3 the other cross-reacting with other enteroviruses, were radioactively labeled with 35S or 32P by in vitro transcription. In paraffin sections histological alterations were assessed semiquantitatively. The animals developed acute myocarditis with myolysis and virus in the myocardium until 14 days after infection. The second stage of the disease was characterized by a persistent inflammatory infiltrate. At this stage no virus could be shown in the myocardium. Antibodies against cardiac myosin appeared 16 days after infection. Autoimmune mechanisms thus seem to be a most relevant factor for persistent inflammation after the acute viral phase of the disease. PMID:1708625

  13. [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

  14. Functional conservation of Pax6 regulatory elements in humans and mice demonstrated with a novel transgenic reporter mouse

    PubMed Central

    Tyas, David A; Simpson, T Ian; Carr, Catherine B; Kleinjan, Dirk A; van Heyningen, Veronica; Mason, John O; Price, David J

    2006-01-01

    Background The Pax6 transcription factor is expressed during development in the eyes and in specific CNS regions, where it is essential for normal cell proliferation and differentiation. Mice lacking one or both copies of the Pax6 gene model closely humans with loss-of-function mutations in the PAX6 locus. The sequence of the Pax6/PAX6 protein is identical in mice and humans and previous studies have shown structural conservation of the gene's regulatory regions. Results We generated a transgenic mouse expressing green fluorescent protein (GFP) and neomycin resistance under the control of the entire complement of human PAX6 regulatory elements using a modified yeast artificial chromosome (YAC). Expression of GFP was studied in embryos from 9.5 days on and was confined to cells known to express Pax6. GFP expression was sufficiently strong that expressing cells could be distinguished from non-expressing cells using flow cytometry. Conclusion This work demonstrates the functional conservation of the regulatory elements controlling Pax6/PAX6 expression in mice and humans. The transgene provides an excellent tool for studying the functions of different Pax6/PAX6 regulatory elements in controlling Pax6 expression in animals that are otherwise normal. It will allow the analysis and isolation of cells in which Pax6 is activated, irrespective of the status of the endogenous locus. PMID:16674807

  15. Transgenic mice overexpressing APP and transforming growth factor-beta1 feature cognitive and vascular hallmarks of Alzheimer's disease.

    PubMed

    Ongali, Brice; Nicolakakis, Nektaria; Lecrux, Clotilde; Aboulkassim, Tahar; Rosa-Neto, Pedro; Papadopoulos, Panayiota; Tong, Xin-Kang; Hamel, Edith

    2010-12-01

    High brain levels of amyloid-β (Aβ) and transforming growth factor-β1 (TGF-β1) have been implicated in the cognitive and cerebrovascular alterations of Alzheimer's disease (AD). We sought to investigate the impact of combined increases in Aβ and TGF-β1 on cerebrovascular, neuronal, and mnemonic function using transgenic mice overproducing these peptides (A/T mice). In particular, we measured cerebrovascular reactivity, evoked cerebral blood flow and glucose uptake during brain activation, cholinergic status, and spatial memory, along with cerebrovascular fibrosis, amyloidosis, and astrogliosis, and their evolution with age. An assessment of perfusion and metabolic responses was considered timely, given ongoing efforts for their validation as AD biomarkers. Relative to wild-type littermates, A/T mice displayed an early progressive decline in cerebrovascular dilatory ability, preserved contractility, and reduction in constitutive nitric oxide synthesis that establishes resting vessel tone. Altered levels of vasodilator-synthesizing enzymes and fibrotic proteins, resistance to antioxidant treatment, and unchanged levels of the antioxidant enzyme, superoxide dismutase-2, accompanied these impairments. A/T mice featured deficient neurovascular and neurometabolic coupling to whisker stimulation, cholinergic denervation, cerebral and cerebrovascular Aβ deposition, astrocyte activation, and impaired Morris water maze performance, which gained severity with age. The combined Aβ- and TGF-β1-driven pathology recapitulates salient cerebrovascular, neuronal, and cognitive AD landmarks and yields a versatile model toward highly anticipated diagnostic and therapeutic tools for patients featuring Aβ and TGF-β1 increments. PMID:21088218

  16. Radiographic features of bone in several strains of laboratory mice and of their tumours induced by bone-seeking radionuclides.

    PubMed

    Loutit, J F; Corp, M J; Ardran, G M

    1976-11-01

    The natural radiographic appearance of the various bones of the skeleton are described for several strains of laboratory mice. The Harwell substrains of CBA, A and 101 are generally similar and become osteoporotic on ageing. Harwell C57BL have similar, but more delicately chiseled, bones. Harwell C3H mice have bones with stouter cortices and may show osteosclerosis on ageing. CF1 females (donated by Dr M. Finkel) showed osteosclerosis and osteophytic outgrowths when aged. NMRI mice (donated by Dr A. Luz) appeared larger than the pure-strain Harwell mice. In general, mouse bones are simple tubular structures with an ivory cortex and a marrow cavity. Cancellous trabecular bone is scanty, even in vertebrae, flat bones and the metaphyses of long bones. Bone-seeking radionuclides administered to mice lead to skeletal tumours: (a) osteosarcomata, which are commonly radio-opaque to a variable degree owing to calcified tumour bone, but which may be osteolytic, (b) primitive mesenchymal (angio-) sarcomata which are non-osteogenic and osteolytic, (c) fibrosarcomata--which also are osteolytic--and to local or general lymphomata from irradiation of parental cells in bone marrow, but no special radiological features have been found associated with these last-named tumours. PMID:1069700

  17. 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

  18. Featured Article: Accelerated decline of physical strength in peroxiredoxin-3 knockout mice.

    PubMed

    Zhang, Yong-Gang; Wang, Li; Kaifu, Tomonori; Li, Jingmin; Li, Xiaoyan; Li, Lianqin

    2016-07-01

    As a member of peroxiredoxin family, peroxiredoxin-3 plays a major role in the control of mitochondrial level of reactive oxygen species. During the breeding of experimental mice, we noticed that the peroxiredoxin-3 knockout mice were listless with aging. In the present study, we compared the swimming exercise performance and oxidative status between peroxiredoxin-3 knockout mice (n = 15) and wild-type littermates (n = 15). At the age of 10 months, the physical strength of peroxiredoxin-3 knockout mice was much lower than the wild-type littermates. Increased oxidative damage and decreased mitochondrial DNA copy number of the animal skeletal muscles were observed in peroxiredoxin-3 knockout mice as compared to that in the wild-type littermates. In addition, we found increased apoptotic cells in the brains of peroxiredoxin-3 knockout mice. Our results suggest that the deficiency of peroxiredoxin-3 induces accelerated oxidative stress and mitochondrial impairment, resulting in the decrease of energy supply and cellular activities. Peroxiredoxin-3 might be involved in the inhibition of aging process. PMID:27037278

  19. 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.

  20. Anatomic, Hematologic, and Biochemical Features of C57BL/6NCrl Mice Maintained on Chronic Oral Corticosterone

    PubMed Central

    Cassano, Amy E; White, Julie R; Penraat, Kelley A; Wilson, Christopher D; Rasmussen, Skye; Karatsoreos, Ilia N

    2012-01-01

    Metabolic syndrome is a condition that typically includes central obesity, insulin resistance, glucose intolerance, dyslipidemia, and hypertension. Disruption of the hypothalamic–pituitary–adrenal axis, a regulator of corticosterone secretion, occurs in some cases of metabolic syndrome and obesity, and Cushing hypercortisolemia is associated with obesity and metabolic disorders. We therefore assessed anatomic and clinical pathology in C57BL/6NCrl mice to evaluate the effects of chronic corticosterone in the drinking water at doses of 25, 50, and 100 μg/mL for 25 d. Treated mice developed obesity, glucose intolerance, electrolyte aberrations, and dyslipidemia that were dose-dependent and most severe in the 100-μg/mL treatment group. To evaluate return to normal function, additional C57BL/6NCrl mice received corticosterone-free water for 2 wk after the 25-d treatment period. According to results of gross examination, mice appeared to recover within days of exogenous corticosterone withdrawal; however, adrenal gland vacuolation and protein, lipid, and electrolyte abnormalities persisted. Together, these findings support chronic corticosterone exposure through the drinking water as a potentially useful, noninvasive method to induce some features of metabolic syndrome. PMID:23114038

  1. 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.

  2. 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

  3. Hydrogen Sulfide Prevents and Partially Reverses Ozone-Induced Features of Lung Inflammation and Emphysema in Mice.

    PubMed

    Li, Feng; Zhang, Pengyu; Zhang, Min; Liang, Li; Sun, Xiaoyuan; Li, Min; Tang, Yueqin; Bao, Aihua; Gong, Jicheng; Zhang, Junfeng; Adcock, Ian; Chung, Kian Fan; Zhou, Xin

    2016-07-01

    Hydrogen sulfide (H2S), a novel signaling gasotransmitter in the respiratory system, may have antiinflammatory properties in the lung. We examined the preventive and therapeutic effects of H2S on ozone-induced features of lung inflammation and emphysema. C57/BL6 mice were exposed to ozone or filtered air over 6 weeks. Sodium hydrogen sulfide (NaHS), an H2S donor, was administered to the mice either before ozone exposure (preventive effect) or after completion of 6 weeks of ozone exposure (therapeutic effect). The ozone-exposed mice developed emphysema, measured by micro-computed tomography and histology, airflow limitation, measured by the forced maneuver system, and increased lung inflammation with augmented IL-1β, IL-18, and matrix metalloproteinase-9 (MMP-9) gene expression. Ozone-induced changes were associated with increased Nod-like receptor pyrin domain containing 3 (NLRP3)-caspase-1 activation and p38 mitogen-activated protein kinase phosphorylation and decreased Akt phosphorylation. NaHS both prevented and reversed lung inflammation and emphysematous changes in alveolar space. In contrast, NaHS prevented, but did not reverse, ozone-induced airflow limitation and bronchial structural remodeling. In conclusion, NaHS administration prevented and partially reversed ozone-induced features of lung inflammation and emphysema via regulation of the NLRP3-caspase-1, p38 mitogen-activated protein kinase, and Akt pathways. PMID:26731380

  4. 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

  5. Clinicopathologic features of young and old sphha/sphha mice. Mutants with congenital hemolytic anemia.

    PubMed Central

    Maggio-Price, L.; Russell, R.; Wolf, N. S.; Alpers, C. E.; Engel, D.

    1988-01-01

    A colony of mice with congenital hemolytic anemia, sphha/sphha, were evaluated over a 3-year period. Prominent findings included decreased survivability, reticulocytosis, increased peripheral blood leukocytes, extramedullary hematopoiesis in liver and spleen, lymphoid hyperplasia and membranoproliferative glomerulonephritis. Older (12 to 21 months) anemic animals had elevated serum levels of IgG1 and IgA. There was deposition of C3, IgG, IgM, and IgA in renal glomeruli of both control and anemic mice, but deposition of IgM and IgA was more prominent and widely distributed in anemic animals and correlated with mesangial expansion and the presence of electron dense deposits in the mesangium and in glomerular capillary walls. Prominent renal tubular hemosiderosis was noted in young and old anemic mice. The relation between the hemolytic anemia and glomerular disease is unclear but these mice may be an animal model useful for exploration of changes attendant with chronic hemolysis and evaluation of renal disease that accompanies hemolytic anemia. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:3414779

  6. Combined Sensitization of Mice to Extracts of Dust Mites, Ragweed and Aspergillus Breaks through Tolerance and Establishes Chronic Features of Asthma in Mice

    PubMed Central

    Goplen, Nicholas; Karim, M. Zunayet; Liang, Qiaoling; Gorska, Magdalena M; Rozario, Sadee; Guo, Lei; Alam, Rafeul

    2009-01-01

    Background Existing asthma models develop tolerance when chronically exposed to the same allergen. Objective To establish a chronic model that sustains features of asthma long after discontinuation of allergen exposure. Methods We immunized and exposed mice to a combination of single, double or triple allergens (dust-mite, ragweed, and Aspergillus) intranasally for 8 weeks. Airway hyperreactivity and morphological features of asthma were studied 3 weeks after the allergen exposure. Signaling effects of the allergens were studied on dendritic cells. Results Sensitization and repeated exposure to a single allergen induced tolerance. Sensitization to double, and especially triple allergens broke through tolerance and established AHR, eosinophilic inflammation, mast cell and smooth muscle hyperplasia, mucus production and airway remodeling that persisted at least 3 weeks after allergen exposure. Mucosal exposure to triple allergens in the absence of an adjuvant was sufficient to induce chronic airway inflammation. Anti-IL5 and -IL13 antibodies inhibited inflammation and AHR in the acute asthma model but not in the chronic triple allergen model. Multiple allergens produce a synergy in p38 MAPK signaling and maturation of dendritic cells, which provides a heightened T cell co-stimulation at a level that cannot be achieved with a single allergen. Conclusions Sensitivity to multiple allergens leads to chronic asthma in mice. Multiple allergens synergize in dendritic cell signaling and T cell stimulation that allows escape from the single allergen-associated tolerance development. Clinical Implications We have developed a model of chronic asthma that allows for the study and treatment of long-lasting features of asthma obviating the need for acute de novo allergen challenges. PMID:19348928

  7. S-adenosylmethionine reduces the progress of the Alzheimer-like features induced by B-vitamin deficiency in mice.

    PubMed

    Fuso, Andrea; Nicolia, Vincenzina; Ricceri, Laura; Cavallaro, Rosaria A; Isopi, Elisa; Mangia, Franco; Fiorenza, Maria Teresa; Scarpa, Sigfrido

    2012-07-01

    Methylation reactions linked to homocysteine in the one-carbon metabolism are increasingly elicited in Alzheimer's disease, although the association of hyperhomocysteinemia and of low B vitamin levels with the disease is still debated. We previously demonstrated that hyperhomocysteinemia and DNA hypomethylation induced by B vitamin deficiency are associated with PSEN1 and BACE1 overexpression and amyloid production. The present study is aimed at assessing S-adenosylmethionine effects in mice kept under a condition of B vitamin deficiency. To this end, TgCRND8 mice and wild-type littermates were assigned to control or B vitamin deficient diet, with or without S-adenosylmethionine supplementation. We found that S-adenosylmethionine reduced amyloid production, increased spatial memory in TgCRND8 mice and inhibited the upregulation of B vitamin deficiency-induced PSEN1 and BACE1 expression and Tau phosphorylation in TgCRND8 and wild-type mice. Furthermore, S-adenosylmethionine treatment reduced plaque spreading independently on B vitamin deficiency. These results strengthen our previous observations on the possible role of one-carbon metabolism in Alzheimer's disease, highlighting hyperhomocysteinemia-related mechanisms in dementia onset/progression and encourage further studies aimed at evaluating the use of S-adenosylmethionine as a potential candidate drug for the treatment of the disease. PMID:22221883

  8. 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.

  9. Triple monoamine uptake inhibitors demonstrate a pharmacologic association between excessive drinking and impulsivity in high-alcohol-preferring (HAP) mice.

    PubMed

    O'Tousa, David S; Warnock, Kaitlin T; Matson, Liana M; Namjoshi, Ojas A; Linn, Michael Van; Tiruveedhula, Veera Venkata; Halcomb, Meredith E; Cook, James; Grahame, Nicholas J; June, Harry L

    2015-03-01

    Approximately 30% of current drinkers in the United States drink excessively, and are referred to as problem/hazardous drinkers. These individuals, who may not meet criteria for alcohol abuse or dependence, comprise binge, heavy drinkers, or both. Given their high prevalence, interventions that reduce the risk of binge and heavy drinking have important public health implications. Impulsivity has been repeatedly associated with excessive drinking in the clinical literature. As impulsivity is correlated with, and may play a critical role in, the initiation and maintenance of excessive drinking, this behavior may be an important target for therapeutic intervention. Hence, a better understanding of pharmacological treatments capable of attenuating excessive drinking and impulsivity may markedly improve clinical outcomes. The high-alcohol-preferring (HAP) mice represent a strong rodent model to study the relationship between impulsivity and excessive alcohol drinking, as recent evidence indicates they consume high levels of alcohol throughout their active cycle and are innately impulsive. Using this model, the present study demonstrates that the triple monoamine uptake inhibitors (TUIs) amitifadine and DOV 102, 677 effectively attenuate binge drinking, heavy drinking assessed via a 24-hour free-choice assay, and impulsivity measured by the delay discounting procedure. In contrast, 3-PBC, a GABA-A α1 preferring ligand with mixed agonist-antagonist properties, attenuates excessive drinking without affecting impulsivity. These findings suggest that in HAP mice, monoamine pathways may predominate as a common mechanism underlying impulsivity and excessive drinking, while the GABAergic system may be more salient in regulating excessive drinking. We further propose that TUIs such as amitifadine and DOV 102, 677 may be used to treat the co-occurrence of impulsivity and excessive drinking. PMID:24118509

  10. 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. PMID:22287557

  11. 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. PMID:25765285

  12. Support vector machines using EEG features of cross-frequency coupling can predict treatment outcome in Mecp2-deficient mice.

    PubMed

    Colic, Sinisa; Wither, Robert G; Min Lang; Zhang Liang; Eubanks, James H; Bardakjian, Berj L

    2015-08-01

    Anti-convulsive drug treatments of epilepsy typically produce varied outcomes from one patient to the next, often necessitating patients to go through several anticonvulsive drug trials until an appropriate treatment is found. The focus of this study is to predict treatment outcome using a priori electroencephalogram (EEG) features for a rare genetic model of epilepsy seen in patients with Rett Syndrome. Previous work on Mecp2-deficient mice, exhibiting the symptoms of Rett syndrome, have revealed EEG-based biomarkers that track the pathology well. Specifically the presence of cross-frequency coupling of the delta-like (3-6 Hz) frequency range phase with the fast ripple (400 - 600 Hz) frequency range amplitude in long duration discharges was found to track seizure pathology. Support Vector Machines (SVM) were trained with features generated from phase-amplitude comodulograms and tested on (n=6) Mecp2-deficient mice to predict treatment outcome to Midazolam, a commonly used anti-convulsive drug. Using SVMs it was shown that it is possible to generate a likelihood score to predict treatment outcomes on all of the animal subjects. Identifying the most appropriate treatment a priori would potentially lead to improved treatment outcomes. PMID:26737563

  13. Virological and clinico-pathological features of orf virus infection in experimentally infected rabbits and mice.

    PubMed

    Cargnelutti, J F; Masuda, E K; Martins, M; Diel, D G; Rock, D L; Weiblen, R; Flores, E F

    2011-01-01

    Many aspects of the biology of orf virus (ORFV) infection remain poorly understood and attempts to establish animal models have yielded conflicting and non-reproducible results. We herein describe the characterization of ORFV infection and disease in rabbits and mice. A protocol of intradermal inoculation was employed to inoculate 10(8.5)TCID₅₀/mL of ORFV strain IA-82 in the skin of ears, of the back and labial commissures. All inoculated rabbits presented a clinical course characterized by erythema, macules, papules/vesicles or pustules that eventually dried originating scabs. Local signs started around days 3 and 4 post-inoculation (pi) and lasted 3-10 days. Virus was recovered from lesions between days 2 and 14pi. Histological examination of lesions revealed focal proliferative dermatitis with ballooning degeneration and eosinophilic intracytoplasmic inclusion bodies in keratinocytes, histological hallmarks of contagious ecthyma in sheep. A similar, albeit milder clinical course occurred in 5/10 inoculated mice; virus was recovered from lesions from three animals. Inoculated lambs - used as controls - developed severe lesions of contagious ecthyma. VN tests performed at day 28pi failed to detect neutralizing antibodies in all inoculated animals. In contrast, convalescent rabbit sera were positive by ELISA at dilutions from 100 to 400. These results show that rabbits are susceptible to ORFV infection and thus may be used to study selected aspects of ORFV biology. PMID:20833245

  14. Immunoregulation of genetically controlled acquired responses to Leishmania donovani infection in mice: demonstration and characterization of suppressor T cells in noncure mice.

    PubMed Central

    Blackwell, J M; Ulczak, O M

    1984-01-01

    On a B10 genetic background, genes in the I region of H-2 influence the development of acquired T-cell mediated immunity to Leishmania donovani infection in mice. In previous studies, noncure in H-2d mice could be abrogated by pretreatments with cyclophosphamide or sublethal irradiation. The prophylactic effect of these pretreatments was consistent with deletion of the precursors of suppressor T cells suppressing T-cell-mediated immune responses. In this study, cell transfer experiments provide direct evidence for the role of suppressor T cells in the noncure response. T-cell-enriched populations isolated from the spleens of B10.D2/n mice infected 30, 61, or 85 days previously reversed the prophylactic effect of sublethal irradiation when injected before infection into B10.D2/n mice that had received 550 rads. B-cell-enriched populations failed to transfer suppression in this manner, and T-cell-enriched populations from the spleens of normal B10.D2/n mice had only a transient effect on liver parasite loads. Transfer of suppression with the T-cell-enriched populations from infected donors was abrogated by pretreatment with anti-Thy-1.2 and anti-Lyt-1.2 antisera plus complement but not by pretreatment with anti-Lyt-2.2 plus complement, indicating that the suppressor T cell involved has an Lyt-1+2- surface phenotype. Results are discussed in relation to the possible mechanism of H-2-linked control. PMID:6231248

  15. Morphological and electrophysiological features of motor neurons and putative interneurons in the dorsal vagal complex of rats and mice

    PubMed Central

    Gao, Hong; Glatzer, Nicholas R.; Williams, Kevin W.; Derbenev, Andrei V.; Liu, Dan; Smith, Bret N.

    2009-01-01

    The dorsal motor nucleus of the vagus (DMV) contains preganglionic motor neurons that control viscera along the subdiaphragmatic digestive tract, but may also contain neurons that do not project to the viscera. Neurons that expressed EGFP 60-72 h subsequent to PRV-152 inoculation of vagal terminals in the stomach wall were targeted for whole-cell patch-clamp recording and biocytin filling in transverse brainstem slices from rats and their quantitative morphological and electrophysiological characteristics were compared with uninfected cells. Over 90% of PRV-152 labeled neurons were also labeled subsequent to intraperitoneal injection of FluoroGold, indicating most were preganglionic motor neurons. In reconstructed neurons with an identifiable axon trajectory, two cellular subtypes were distinguished. The axon projected ventrolaterally from the DMV in 44 of 49 cells and these were likely to be vagal motor neurons. Axons of other neurons ramified within the nucleus tractus solitarius (NTS) or DMV. These cells were smaller and otherwise morphologically distinct from putative motor neurons. Transgenic mice with GFP-expressing inhibitory neurons (i.e., GIN mice) were used to identify a GABAergic subset vagal neurons. These neurons had locally-ramifying axons and formed a morphologically distinct subset of DMV cells, which were similar in size and axon trajectory to GABAergic neurons in the NTS. Most neurons in the DMV therefore possess morphological features of motor neurons, but locally projecting cells and inhibitory neurons with distinct morphological features are also found within the DMV. These cells likely contribute to regulation of vagal function. PMID:19619517

  16. 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 ...

  17. 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

  18. GPR21 KO mice demonstrate no resistance to high fat diet induced obesity or improved glucose tolerance.

    PubMed

    Wang, Jinghong; Pan, Zheng; Baribault, Helene; Chui, Danny; Gundel, Caroline; Véniant, Murielle

    2016-01-01

    Gpr21 KO mice generated with Gpr21 KO ES cells obtained from Deltagen showed improved glucose tolerance and insulin sensitivity when fed a high fat diet. Further mRNA expression analysis revealed changes in Rabgap1 levels and raised the possibility that Rabgap1 gene may have been modified. To assess this hypothesis a new Gpr21 KO mouse line using TALENS technology was generated. Gpr21 gene deletion was confirmed by PCR and Gpr21 and Rabgap1 mRNA expression levels were determined by RT-PCR. The newly generated Gpr21 KO mice when fed a normal or high fat diet chow did not maintain their improved metabolic phenotype. In conclusion, Rabgap1 disturbance mRNA expression levels may have contributed to the phenotype of the originally designed Gpr21 KO mice. PMID:27081476

  19. GPR21 KO mice demonstrate no resistance to high fat diet induced obesity or improved glucose tolerance

    PubMed Central

    Wang, Jinghong; Pan, Zheng; Baribault, Helene; Chui, Danny; Gundel, Caroline; Véniant, Murielle

    2016-01-01

    Gpr21 KO mice generated with Gpr21 KO ES cells obtained from Deltagen showed improved glucose tolerance and insulin sensitivity when fed a high fat diet. Further mRNA expression analysis revealed changes in Rabgap1 levels and raised the possibility that Rabgap1 gene may have been modified. To assess this hypothesis a new Gpr21 KO mouse line using TALENS technology was generated. Gpr21 gene deletion was confirmed by PCR and Gpr21 and Rabgap1 mRNA expression levels were determined by RT-PCR. The newly generated Gpr21 KO mice when fed a normal or high fat diet chow did not maintain their improved metabolic phenotype. In conclusion, Rabgap1 disturbance mRNA expression levels may have contributed to the phenotype of the originally designed Gpr21 KO mice. PMID:27081476

  20. 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

  1. 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

  2. Transgenic mice expressing an intracellular fluorescent fusion of angiotensin II demonstrate renal thrombotic microangiopathy and elevated blood pressure

    PubMed Central

    Redding, K. M.; Chen, B. L.; Singh, A.; Re, R. N.; Navar, L. G.; Seth, D. M.; Sigmund, C. D.; Tang, W. W.

    2010-01-01

    We have generated transgenic mice that express angiotensin II (ANG II) fused downstream of enhanced cyan fluorescent protein, expression of which is regulated by the mouse metallothionein promoter. The fusion protein, which lacks a secretory signal, is retained intracellularly. In the present study, RT-PCR, immunoblot analyses, whole-animal fluorescent imaging, and fluorescent microscopy of murine embryonic fibroblasts confirm expression of the fusion protein in vivo and in vitro. The transgene is expressed in all tissues tested (including brain, heart, kidney, liver, lung, and testes), and radioimmunoassay of plasma samples obtained from transgenic mice indicate no increase in circulating ANG II over wild-type levels, consistent with intracellular retention of the transgene product. Kidneys from transgenic and corresponding wild-type littermates were histologically evaluated, and abnormalities in transgenic mice consistent with thrombotic microangiopathy were observed; microthrombosis was frequently observed within the glomerular capillaries and small vessels. In addition, systolic and diastolic blood pressures, measured by telemetry (n = 8 for each group), were significantly higher in transgenic mice compared with wild-type littermates. Blood pressure of line A male transgenic mice was 125 ± 1.7 over 97 ± 1.6 compared with 109 ± 1.7 over 83 ± 1.4 mmHg in wild-type littermates (systolic over diastolic). In summary, overexpression of an intracellular fluorescent fusion protein of ANG II correlates with elevated blood pressure and kidney pathology. This transgenic model may be useful to further explore the intracellular renin-angiotensin system and its implication in abnormal kidney function and hypertension. PMID:20363893

  3. Overexpression of ALS-associated p.M337V human TDP-43 in mice worsens disease features compared to wild-type human TDP-43 mice.

    PubMed

    Janssens, Jonathan; Wils, Hans; Kleinberger, Gernot; Joris, Geert; Cuijt, Ivy; Ceuterick-de Groote, Chantal; Van Broeckhoven, Christine; Kumar-Singh, Samir

    2013-08-01

    Mutations in TAR DNA-binding protein 43 (TDP-43) are associated with familial forms of amyotrophic lateral sclerosis (ALS), while wild-type TDP-43 is a pathological hallmark of patients with sporadic ALS and frontotemporal lobar degeneration (FTLD). Various in vitro and in vivo studies have also demonstrated toxicity of both mutant and wild-type TDP-43 to neuronal cells. To study the potential additional toxicity incurred by mutant TDP-43 in vivo, we generated mutant human TDP-43 (p.M337V) transgenic mouse lines driven by the Thy-1.2 promoter (Mt-TAR) and compared them in the same experimental setting to the disease phenotype observed in wild-type TDP-43 transgenic lines (Wt-TAR) expressing comparable TDP-43 levels. Overexpression of mutant TDP-43 leads to a worsened dose-dependent disease phenotype in terms of motor dysfunction, neurodegeneration, gliosis, and development of ubiquitin and phosphorylated TDP-43 pathology. Furthermore, we show that cellular aggregate formation or accumulation of TDP-43 C-terminal fragments (CTFs) are not primarily responsible for development of the observed disease phenotype in both mutant and wild-type TDP-43 mice. PMID:23475610

  4. 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.

  5. 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.

  6. Six features of Medicare coordinated care demonstration programs that cut hospital admissions of high-risk patients.

    PubMed

    Brown, Randall S; Peikes, Deborah; Peterson, Greg; Schore, Jennifer; Razafindrakoto, Carol M

    2012-06-01

    As policy makers seek to slow the growth in Medicare spending, they have appropriately focused attention on beneficiaries with multiple chronic conditions. Many care coordination and disease management programs designed to improve beneficiaries' care and reduce their need for hospitalizations have been tested, but few have been successful. This study, however, found that four of eleven programs that were part of the Medicare Coordinated Care Demonstration reduced hospitalizations by 8-33 percent among enrollees who had a high risk of near-term hospitalization. The six approaches practiced by care coordinators in at least three of the four programs were as follows: supplementing telephone calls to patients with frequent in-person meetings; occasionally meeting in person with providers; acting as a communications hub for providers; delivering evidence-based education to patients; providing strong medication management; and providing timely and comprehensive transitional care after hospitalizations. When care management fees were included, the programs were essentially cost-neutral, but none of these programs generated net savings to Medicare. Our results suggest that incorporating these approaches into medical homes, accountable care organizations, and other policy initiatives could reduce hospitalizations and improve patients' lives. However, the approaches would save money only if care coordination fees were modest and organizations found cost-effective ways to deliver the interventions. PMID:22665827

  7. The development of autoimmune features in aging mice is closely associated with alterations of the peripheral CD4⁺ T-cell compartment.

    PubMed

    Nusser, Anja; Nuber, Natko; Wirz, Oliver F; Rolink, Hannie; Andersson, Jan; Rolink, Antonius

    2014-10-01

    Some signs of potential autoimmunity, such as the appearance of antinuclear antibodies (ANAs) become prevalent with age. In most cases, elderly people with ANAs remain healthy. Here, we investigated whether the same holds true for inbred strains of mice. Indeed, we show that most mice of the C57BL/6 (B6) strain spontaneously produced IgG ANA at 8-12 months of age, showed IgM deposition in kidneys and lymphocyte infiltrates in submandibular salivary glands. Despite all of this, the mice remained healthy. ANA production is likely CD4(+) T-cell dependent, since old (40-50 weeks of age) B6 mice deficient for MHC class II do not produce IgG ANAs. BM chimeras showed that ANA production was not determined by age-related changes in radiosensitive, hematopoietic progenitor cells, and that the CD4(+) T cells that promote ANA production were radioresistant. Thymectomy of B6 mice at 5 weeks of age led to premature alterations in T-cell homeostasis and ANA production, by 15 weeks of age, similar to that in old mice. Our findings suggest that a disturbed T-cell homeostasis may drive the onset of some autoimmune features. PMID:25044476

  8. Development of polycystic kidney disease in juvenile cystic kidney mice: insights into pathogenesis, ciliary abnormalities, and common features with human disease.

    PubMed

    Smith, Laurie A; Bukanov, Nikolay O; Husson, Hervé; Russo, Ryan J; Barry, Tiffany C; Taylor, Ava L; Beier, David R; Ibraghimov-Beskrovnaya, Oxana

    2006-10-01

    Significant progress in understanding the molecular mechanisms of polycystic kidney disease (PKD) has been made in recent years. Translating this understanding into effective therapeutics will require testing in animal models that closely resemble human PKD by multiple parameters. Similar to autosomal dominant PKD, juvenile cystic kidney (jck) mice develop cysts in multiple nephron segments, including cortical collecting ducts, distal tubules, and loop of Henle. The jck mice display gender dimorphism in kidney disease progression with more aggressive disease in male mice. Gonadectomy experiments show that testosterone aggravates the severity of the disease in jck male mice, while female gonadal hormones have protective effects. EGF receptor is overexpressed and mislocalized in jck cystic epithelia, a hallmark of human disease. Increased cAMP levels in jck kidneys and activation of the B-Raf/extracellular signal-regulated kinase pathway are demonstrated. The effect of jck mutation on the expression of Nek8, a NIMA-related (never in mitosis A) kinase, and polycystins in jck cilia is shown for the first time. Nek8 overexpression and loss of ciliary localization in jck epithelia are accompanied by enhanced expression of polycystins along the cilia. The primary cilia in jck kidneys are significantly more lengthened than the cilia in wild-type mice, suggesting a role for Nek8 in controlling ciliary length. Collectively, these data demonstrate that the jck mice should be useful for testing potential therapies and for studying the molecular mechanisms that link ciliary structure/function and cystogenesis. PMID:16928806

  9. 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

  10. 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

    Gesing, Adam; Masternak, Michal M; Lewinski, Andrzej; Karbownik-Lewinska, Malgorzata; Kopchick, John J; Bartke, Andrzej

    2013-06-01

    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

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

    PubMed Central

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

    2013-01-01

    Summary 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. PMID:22846639

  12. 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)

  13. 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

  14. 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

  15. Bispecificity for myelin and neuronal self-antigens is a common feature of CD4 T cells in C57BL/6 mice.

    PubMed

    Lucca, Liliana E; Desbois, Sabine; Ramadan, Abdulraouf; Ben-Nun, Avraham; Eisenstein, Miriam; Carrié, Nadège; Guéry, Jean-Charles; Sette, Alessandro; Nguyen, Phuong; Geiger, Terrence L; Mars, Lennart T; Liblau, Roland S

    2014-10-01

    The recognition of multiple ligands by a single TCR is an intrinsic feature of T cell biology, with important consequences for physiological and pathological processes. Polyspecific T cells targeting distinct self-antigens have been identified in healthy individuals as well as in the context of autoimmunity. We have previously shown that the 2D2 TCR recognizes the myelin oligodendrocyte glycoprotein epitope (MOG)35-55 as well as an epitope within the axonal protein neurofilament medium (NF-M15-35) in H-2(b) mice. In this study, we assess whether this cross-reactivity is a common feature of the MOG35-55-specific T cell response. To this end, we analyzed the CD4 T cell response of MOG35-55-immunized C57BL/6 mice for cross-reactivity with NF-M15-35. Using Ag recall responses, we established that an important proportion of MOG35-55-specific CD4 T cells also responded to NF-M15-35 in all mice tested. To study the clonality of this response, we analyzed 22 MOG35-55-specific T cell hybridomas expressing distinct TCR. Seven hybridomas were found to cross-react with NF-M15-35. Using an alanine scan of NF-M18-30 and an in silico predictive model, we dissected the molecular basis of cross-reactivity between MOG35-55 and NF-M15-35. We established that NF-M F24, R26, and V27 proved important TCR contacts. Strikingly, the identified TCR contacts are conserved within MOG38-50. Our data indicate that due to linear sequence homology, part of the MOG35-55-specific T cell repertoire of all C57BL/6 mice also recognizes NF-M15-35, with potential implications for CNS autoimmunity. PMID:25135834

  16. Peyer's Patch-Deficient Mice Demonstrate That Mycobacterium avium subsp. paratuberculosis Translocates across the Mucosal Barrier via both M Cells and Enterocytes but Has Inefficient Dissemination ▿

    PubMed Central

    Bermudez, Luiz E.; Petrofsky, Mary; Sommer, Sandra; Barletta, Raúl G.

    2010-01-01

    Mycobacterium avium subsp. paratuberculosis, the agent of Johne's disease, infects ruminant hosts by translocation through the intestinal mucosa. A number of studies have suggested that M. avium subsp. paratuberculosis interacts with M cells in the Peyer's patches of the small intestine. The invasion of the intestinal mucosa by M. avium subsp. paratuberculosis and Mycobacterium avium subsp. hominissuis, a pathogen known to interact with intestinal cells, was compared. M. avium subsp. paratuberculosis was capable of invading the mucosa, but it was significantly less efficient at dissemination than M. avium subsp. hominissuis. B-cell knockout (KO) mice, which lack Peyer's patches, were used to demonstrate that M. avium subsp. paratuberculosis enters the intestinal mucosa through enterocytes in the absence of M cells. In addition, the results indicated that M. avium subsp. paratuberculosis had equal abilities to cross the mucosa in both Peyer's patch and non-Peyer's patch segments of normal mice. M. avium subsp. paratuberculosis was also shown to interact with epithelial cells by an α5β1 integrin-independent pathway. Upon translocation, dendritic cells ingest M. avium subsp. paratuberculosis, but this process does not lead to efficient dissemination of the infection. In summary, M. avium subsp. paratuberculosis interacts with the intestinal mucosa by crossing both Peyer's patches and non-Peyer's patch areas but does not translocate or disseminate efficiently. PMID:20498259

  17. [Features of the B chromosome in Korean wood mice Apodemus peninsulae (Thomas, 1906) from Transbaikalia and the Far East identified by the FISH method].

    PubMed

    Rubtsov, N B; Kartavtseva, I V; Roslik, G V; Karamysheva, T V; Pavlenko, M V; Iwasa, M A; Koh, H S

    2015-03-01

    Korean field mice (Apodemus peninsulae) are widely distributed throughout northeastern Asia, including the Russian Far East, northern China, the Korean peninsula, Sakhalin, and Hokkaido. This mouse species is characterized by a high frequency of animals with B chromosomes differing in their number, morphology, and DNA composition in different geographical regions. For the first time a comparative analysis of DNA probes from B chromosomes with metaphase chromosomes of mice from Transbaikalia, the Far East (including the Russian Far East), Japan, and South Korea was conducted by in situ hybridization. B chromosomes in mice from the Russian Far East were shown to exhibit low variability in DNA content; however, the DNA composition of B chromosomes in species from Transbaikalia and Japan were highly variable. B chromosomes in A. peninsulae from the South Korean population demonstrate minor differences from those from the Russian Far East. We discuss the origin of B chromosomes in the studied region in comparison with previously obtained data for mice from Siberia and the Baikal region, as well as the dispersal routes of the Korean field mouse. PMID:26027373

  18. 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

  19. Persistent hyperactivity and distinctive strategy features in the Morris water maze in 3xTg-AD mice at advanced stages of disease.

    PubMed

    Baeta-Corral, Raquel; Giménez-Llort, Lydia

    2015-04-01

    Search strategies in the Morris water maze provide useful insights on cognitive function that may reveal genotype differences not reflected by escape latency or distance. Its analysis is pointed out as a complementary tool to better define the phenotype and the effect of treatments in animal models in which both cognitive impairment and behavioral symptoms reproduce the clinical complexity of the Alzheimer's disease patient. Here, we studied the performance of 13-month-old male 3xTg-AD mice in 3 different paradigms (cue learning, place task, and probe trial) and as compared with age-matched nontransgenic mice. The quantitative analysis (escape latency, distance, and speed) showed that in all tasks, the cognitive performance of 3xTg-AD mice was interfered with by a persistent hyperactive pattern. Their worse cognitive function was revealed by the qualitative features of nonsearch behaviors (floating and circling) and search strategies (single and /mixed, goal directed and nongoal directed). The search pattern was based on mixed and nongoal-directed strategies, in contrast to the single and goal-directed strategies used by controls. In the place task, poor cognitive flexibility of 3xTg-AD mice was also shown in persistence of search in the cue-trained position and the need to correct the strategy to find the new location. Trials involving a naïve situation (first trial of the cue task) or the difficulty of a new task (first trial of the place task and the probe trial) were the most suitable to show the deficits. This qualitative analysis may also be useful in the assessment of preventive or therapeutical treatments. PMID:25730122

  20. Syndromic features and mild cognitive impairment in mice with genetic reduction on p300 activity: Differential contribution of p300 and CBP to Rubinstein-Taybi syndrome etiology.

    PubMed

    Viosca, Jose; Lopez-Atalaya, Jose P; Olivares, Roman; Eckner, Richard; Barco, Angel

    2010-01-01

    Rubinstein-Taybi syndrome (RSTS) is a complex autosomal-dominant disease characterized by mental and growth retardation and skeletal abnormalities. A majority of the individuals diagnosed with RSTS carry heterozygous mutation in the gene CREBBP, but a small percentage of cases are caused by mutations in EP300. To investigate the contribution of p300 to RSTS pathoetiology, we carried out a comprehensive and multidisciplinary characterization of p300(+/-) mice. These mice exhibited facial abnormalities and impaired growth, two traits associated to RSTS in humans. We also observed abnormal gait, reduced swimming speed, enhanced anxiety in the elevated plus maze, and mild cognitive impairment during the transfer task in the water maze. These analyses demonstrate that p300(+/-) mice exhibit phenotypes that are reminiscent of neurological traits observed in RSTS patients, but their comparison with previous studies on CBP deficient strains also indicates that, in agreement with the most recent findings in human patients, the activity of p300 in cognition is likely less relevant or more susceptible to compensation than the activity of CBP. PMID:19822209

  1. [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. PMID:26993065

  2. Cutaneous barrier function after cold exposure in hairless mice: a model to demonstrate how cold interferes with barrier homeostasis among workers in the fish-processing industry.

    PubMed

    Halkier-Sørensen, L; Menon, G K; Elias, P M; Thestrup-Pedersen, K; Feingold, K R

    1995-03-01

    Dry skin and eczema only seldomly occur in workers in the Danish fish-processing industry (FPI) during work, when their fingers and palms have a low skin surface temperature, low transepidermal water loss (TEWL), and a high capacitance. However, shortly after work, when the skin temperature has become normal, TEWL levels increase to above normal, and capacitance decreases to below normal, followed by the development of dry skin or chapping, which subsequently revert to normal over a period of hours. These observations suggest that workers in the FPI may have a defect in skin barrier function, which is, however, masked by a low skin temperature, resulting in misleadingly low TEWL levels during work. To test this hypothesis, we disrupted the permeability barrier in hairless mice with topical acetone, and exposed the treated skin to ice for 3.5 h. Although TEWL rates immediately after cold exposure were low, suggesting normal barrier recovery, TEWL increased to levels slightly above pre-cold exposure levels (i.e. levels just after the barrier was disrupted with acetone) when the skin temperature reverted to normal (> or = 15 min). The changes in TEWL were paralleled by equivalent changes in percutaneous penetration of the electron-dense tracer lanthanum nitrate. This indicates that cold masks a defective barrier, and inhibits barrier repair. After a few hours at ambient temperatures, normal barrier recovery was observed. Electron microscopy revealed empty or partially empty lamellar bodies during the first 30 min post-cold exposure. After 1 h the majority of nascent LBs displayed normal morphology. Moreover, histochemical studies showed a delayed reappearance of stratum corneum intercellular lipids following cold exposure. These results demonstrate that cold exposure prevents barrier recovery after acetone disruption, and provide an explanation for the occupational dermatosis observed in the fish-processing industry and related occupations. PMID:7718455

  3. 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

  4. 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

  5. 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

  6. Studies in mice, hamsters, and rats demonstrate that repression of hepatic apoA-I expression by taurocholic acid in mice is not mediated by the farnesoid-X-receptor

    PubMed Central

    Gardès, Christophe; Blum, Denise; Bleicher, Konrad; Chaput, Evelyne; Ebeling, Martin; Hartman, Peter; Handschin, Corinne; Richter, Hans; Benson, G. Martin

    2011-01-01

    It is claimed that apoA-I expression is repressed in mice by cholic acid (CA) and its taurine conjugate, taurocholic acid (TCA) via farnesoid X receptor (FXR) activation. We measured apoA-I expression in mice, hamsters, and rats treated with highly potent and selective synthetic FXR agonists or with TCA. All of the synthetic agonists bound to FXR with high affinity in a scintillation proximity assay. However, TCA did not compete with the radioligand up to the highest concentration used (100 μM). The C-site regulatory region of apoA-I, through which FXR has been reported to regulate its expression, is completely conserved across the species investigated. In both male and female human apoA-I-transgenic mice, we reproduced the previously reported strong inhibition of human apoA-I expression upon treatment with the typical supraphysiological dose of TCA used in such studies. However, in contrast to some previous reports, TCA did not repress murine apoA-I expression in the same mice. Also, more-potent and -selective FXR agonists did not affect human or murine apoA-I expression in this model. In LDL receptor-deficient mice and Golden Syrian hamsters, selective FXR agonists did not affect apoA-I expression, whereas in Wistar rats, some even increased apoA-I expression. In conclusion, selective FXR agonists do not repress apoA-I expression in rodents. Repression of human apoA-I expression by TCA in transgenic mice is probably mediated through FXR-independent mechanisms. PMID:21464203

  7. Constitutive expression of GsαR201C in mice produces a heritable, direct replica of human fibrous dysplasia bone pathology and demonstrates its natural history

    PubMed Central

    Saggio, Isabella; Remoli, Cristina; Spica, Emanuela; Cersosimo, Stefania; Sacchetti, Benedetto; Robey, Pamela G.; Holmbeck, Kenn; Cumano, Ana; Boyde, Alan; Bianco, Paolo; Riminucci, Mara

    2014-01-01

    Fibrous dysplasia of bone (FD) is a crippling skeletal disease associated with post zygotic mutations (R201C, R201H) of the gene encoding the α subunit of the stimulatory G protein, Gs. By causing a characteristic structural subversion of bone and bone marrow, the disease results in deformity, hypomineralization, and fracture of the affected bones, with severe morbidity arising in childhood or adolescence. Lack of inheritance of the disease in humans is thought to reflect embryonic lethality of germline-transmitted activating Gsα mutations, which would only survive through somatic mosaicism. We have generated multiple lines of mice that express GsαR201C constitutively and develop an inherited, histopathologically exact replica of human FD. Robust transgene expression in neonatal and embryonic tissues, and embryonic stem (ES) cells was associated with normal development of skeletal tissues and differentiation of skeletal cells. As in humans, FD lesions in mice developed only in the postnatal life; a defined spatial and temporal pattern characterized the onset and progression of lesions across the skeleton. In individual bones, lesions developed through a sequence of three distinct histopathological stages: a primary modeling phase defined by endosteal/medullary excess bone formation, and normal resorption; a secondary phase, with excess, inappropriate remodeling; and a tertiary fibrous dysplastic phase, which reproduced a full-blown replica of the human bone pathology in mice of age ≥1 year. Gsα mutations are sufficient to cause FD, and are per se compatible with germline transmission and normal embryonic development in mice. Our novel murine lines constitute the first model of FD. PMID:24764158

  8. Pathogenicity of Hantaan Virus in Newborn Mice: Genetic Reassortant Study Demonstrating that a Single Amino Acid Change in Glycoprotein G1 Is Related to Virulence

    PubMed Central

    Ebihara, Hideki; Yoshimatsu, Kumiko; Ogino, Michiko; Araki, Koichi; Ami, Yasushi; Kariwa, Hiroaki; Takashima, Ikuo; Li, Dexin; Arikawa, Jiro

    2000-01-01

    Two Hantaan virus strains, clone 1 (cl-1), which is virulent in newborn mice, and its attenuated mutant (mu11E10), were used to examine the pathogenesis of Hantaan virus infection in a mouse model and identify virus factors relating to virulence. After subcutaneous inoculation of newborn BALB/c mice, cl-1 caused fatal disease with high viral multiplication in peripheral organs, but mu11E10 produced nonfatal infection with a low level of virus multiplication. Intracerebral inoculation of either strain caused fatal disease. Histopathological changes in the dead animals were prominent in the brain, indicating that the brain is the target organ and produces the fatal outcome. These results indicate that mu11E10 has a generally less virulent phenotype, and because of decreased multiplication in peripheral tissues, neuroinvasiveness is also decreased. An experiment with genetic reassortant viruses showed that in newborn mice the M segment is the most related to virulence and the L segment is partly related. Sequence comparison detected a single deduced amino acid change (cl-1 Ile to mu11E10 Thr) at amino acid number 515 in glycoprotein G1. One nucleotide change, but no amino acid substitution, was observed in the noncoding region of the L segment. In mouse brain microvascular endothelial cells in vitro, viruses possessing a cl-1-derived M segment grew more rapidly than viruses containing a mu11E10-derived M segment. These results suggest that the single amino acid change in the glycoprotein alters peripheral growth, which affects invasion of the central nervous system in mice. PMID:10982372

  9. Studies of group B streptococcal infection in mice deficient in complement component C3 or C4 demonstrate an essential role for complement in both innate and acquired immunity.

    PubMed Central

    Wessels, M R; Butko, P; Ma, M; Warren, H B; Lage, A L; Carroll, M C

    1995-01-01

    Group B streptococci (GBS) cause sepsis and meningitis in neonates and serious infections in adults with underlying chronic illnesses. Specific antibodies have been shown to be an important factor in protective immunity for neonates, but the role of serum complement is less well defined. To elucidate the function of the complement system in immunity to this pathogen, we have used the approach of gene targeting in embryonic stem cells to generate mice totally deficient in complement component C3. Comparison of C3-deficient mice with mice deficient in complement component C4 demonstrated that the 50% lethal dose for GBS infection was reduced by approximately 50-fold and 25-fold, respectively, compared to control mice. GBS were effectively killed in vitro by human blood leukocytes in the presence of specific antibody and C4-deficient serum but not C3-deficient serum. The defective opsonization by C3-deficient serum in vitro was corroborated by in vivo studies in which passive immunization of pregnant dams with specific antibodies conferred protection from GBS challenge to normal and C4-deficient pups but not C3-deficient pups. These results indicate that the alternative pathway is sufficient to mediate effective opsonophagocytosis and protective immunity to GBS in the presence of specific antibody. In contrast, the increased susceptibility to infection of non-immune mice deficient in either C3 or C4 implies that the classical pathway plays an essential role in host defense against GBS infection in the absence of specific immunity. Images Fig. 1 PMID:8524789

  10. 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

  11. Mice with a selective impairment of IFN-γ signaling in macrophage lineage cells demonstrate the critical role of IFN-γ activated macrophages for the control of protozoan parasitic infections in vivo1, 2

    PubMed Central

    Lykens, Jennifer E.; Terrell, Catherine E.; Zoller, Erin E.; Divanovic, Senad; Trompette, Aurelien; Karp, Christopher L.; Aliberti, Julio; Flick, Matthew J.; Jordan, Michael B.

    2010-01-01

    IFN-γ has long been recognized as a cytokine with potent and varied effects in the immune response. While its effects on specific cell types have been well studied in vitro, its in vivo effects are less clearly understood because of its diverse actions on many different cell types. While control of multiple protozoan parasites is thought to depend critically on the direct action of IFN-γ on macrophages, this premise has never been directly proven in vivo. In order to more directly examine the effects of IFN-γ on cells of the macrophage lineage in vivo, we generated mice called the ‘Macrophages Insensitive to Interferon Gamma’ (MIIG) mice, which express a dominant negative mutant IFN-γ receptor in CD68+ cells: monocytes, macrophages, dendritic cells, and mast cells. Macrophage lineage cells and mast cells from these mice are unable to respond to IFN-γ while other cells are able to produce and respond to this cytokine normally. When challenged in vitro, macrophages from MIIG mice were unable produce NO or kill Trypanosoma cruzi or Leishmania major after priming with IFN-γ. Furthermore, MIIG mice demonstrated impaired parasite control and heightened mortality after T. cruzi, L. major, and Toxoplasma gondii infection, despite an appropriate IFN-γ response. In contrast, MIIG mice displayed normal control of lymphocytic choriomeningitis virus, despite persistent insensitivity of macrophages to IFN-γ. Thus, the MIIG mouse formally demonstrates for the first time in vivo, the specific importance of direct, IFN-γ mediated activation of macrophages for controlling infection with multiple protozoan parasites. “This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may

  12. Analysis of T cell antigen receptors of myelin basic protein specific T cells in SJL/J mice demonstrates an alpha chain CDR3 motif associated with encephalitogenic T cells.

    PubMed

    Yamamura, T; Kondo, T; Sakanaka, S; Kozovska, M; Geng, T C; Takahashi, K; Tabira, T

    1994-07-01

    Experimental autoimmune encephalomyelitis (EAE) is an animal autoimmune disease mediated by CD4+ T cells. Analysis of TCR expression revealed that limited TCR elements (V beta 8.2, V alpha 2 or 4) were utilized by myelin basic protein (MBP) specific T cells in mice with H-2u haplotype and Lewis rats. The usage of a particular beta chain complementarity determining region 3 (CDR3) motif has also been shown. However, it remains unclear to what extent these observations can be extrapolated. Here we studied the TCR sequences of MBP 89-101/I-A(s) specific T cell clones derived from SJL/J mice, using the polymerase chain reaction on reverse transcribed mRNA. Although the V beta usage was less restricted than in H-2u mice, they predominantly utilized V beta 17a and expressed LGG or related motifs in the V beta-D beta-J beta junctions. Furthermore, a single alpha chain rearrangement between V alpha 1.1 and J alpha BBM142 with no N region diversity was preferentially used. Concordantly, immunization with a peptide corresponding to the alpha chain CDR3 was found to significantly alter the clinical course of EAE. Comparison of the published TCR junctional regions demonstrates that the CDR3 motifs (LGG in beta chain, CA*R*NY motif in alpha chains) are expressed by other encephalitogenic clones. Notably, the CA*R*NY was conserved in PL/J mice clones that recognize a distinct MBP-MHC determinant. It suggests that an antigen-independent mechanism may contribute to conserving the alpha chain motif. The implications of these observations are discussed. PMID:7524642

  13. 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)

  14. 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)

  15. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1979-01-01

    Presents two demonstrations which are intended for chemistry college students. These demonstrations are: (1) enhancement of concentration quenching by micelles; and (2) the thermite lecture demonstration. (HM)

  16. First Demonstration of Transmissible Spongiform Encephalopathy-associated Prion Protein (PrPTSE) in Extracellular Vesicles from Plasma of Mice Infected with Mouse-adapted Variant Creutzfeldt-Jakob Disease by in Vitro Amplification*

    PubMed Central

    Saá, Paula; Yakovleva, Oksana; de Castro, Jorge; Vasilyeva, Irina; De Paoli, Silvia H.; Simak, Jan; Cervenakova, Larisa

    2014-01-01

    The development of variant Creutzfeldt-Jakob disease (vCJD) in three recipients of non-leukoreduced red blood cells from asymptomatic donors who subsequently developed the disease has confirmed existing concerns about the possible spread of transmissible spongiform encephalopathies (TSEs) via blood products. In addition, the presence of disease-associated misfolded prion protein (PrPTSE), generally associated with infectivity, has been demonstrated in the blood of vCJD patients. However, its origin and distribution in this biological fluid are still unknown. Various studies have identified cellular prion protein (PrPC) among the protein cargo in human blood-circulating extracellular vesicles released from endothelial cells and platelets, and exosomes isolated from the conditioned media of TSE-infected cells have caused the disease when injected into experimental mice. In this study, we demonstrate the detection of PrPTSE in extracellular vesicles isolated from plasma samples collected during the preclinical and clinical phases of the disease from mice infected with mouse-adapted vCJD and confirm the presence of the exosomal marker Hsp70 in these preparations. PMID:25157106

  17. 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)

  18. 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)

  19. Intravenous injection of AAVrh10-GALC after the neonatal period in twitcher mice results in significant expression in the central and peripheral nervous systems and improvement of clinical features.

    PubMed

    Rafi, Mohammad A; Rao, Han Zhi; Luzi, Paola; Luddi, Alice; Curtis, Mark T; Wenger, David A

    2015-03-01

    Globoid cell leukodystrophy (GLD) or Krabbe disease is an autosomal recessive disorder resulting from the defective lysosomal enzyme galactocerebrosidase (GALC). The lack of GALC enzyme leads to severe neurological symptoms. While most human patients are infants who do not survive beyond 2 years of age, older patients are also diagnosed. In addition to human patients, several naturally occurring animal models, including dog, mouse, and monkey, have also been identified. The mouse model of Krabbe disease, twitcher (twi) mouse has been used for many treatment trials including gene therapy. Using the combination of intracerebroventricular, intracerebellar, and intravenous (iv) injection of the adeno-associated virus serotype rh10 (AAVrh10) expressing mouse GALC in neonate twi mice we previously have demonstrated a significantly extended normal life and exhibition of normal behavior in treated mice. In spite of the prolonged healthy life of these treated mice and improved myelination, it is unlikely that using multiple injection sites for viral administration will be approved for treatment of human patients. In this study, we have explored the outcome of the single iv injection of viral vector at post-natal day 10 (PND10). This has resulted in increased GALC activity in the central nervous system (CNS) and high GALC activity in the peripheral nervous system (PNS). As we have shown previously, an iv injection of AAVrh10 at PND2 results in a small extension of life beyond the typical lifespan of the untreated twi mice (~40 days). In this study, we report that mice receiving a single iv injection at PND10 had no tremor and continued to gain weight until a few weeks before they died. On average, they lived 20-25 days longer than untreated mice. We anticipate that this strategy in combination with other therapeutic options may be beneficial and applicable to treatment of human patients. PMID:25533112

  20. 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)

  1. Novel NG2-CreERT2 knock-in mice demonstrate heterogeneous differentiation potential of NG2 glia during development.

    PubMed

    Huang, Wenhui; Zhao, Na; Bai, Xianshu; Karram, Khalad; Trotter, Jacqueline; Goebbels, Sandra; Scheller, Anja; Kirchhoff, Frank

    2014-06-01

    NG2 (nerve/glia antigen-2) is a type I transmembrane glycoprotein and also known as chondroitin sulfate proteoglycan 4. In the parenchyma of the central nervous system, NG2-expressing (NG2(+) ) cells have been identified as a novel type of glia with a strong potential to generate oligodendrocytes (OLs) in the developing white matter. However, the differentiation potential of NG2 glia remained controversial, largely attributable to shortcomings of transgenic mouse models used for fate mapping. To minimize these restrictions and to more faithfully mimic the endogenous NG2 expression in vivo, we generated a mouse line in which the open reading frame of the tamoxifen-inducible form of the Cre DNA recombinase (CreERT2) was inserted into the NG2 locus by homologous recombination. Results from this novel mouse line demonstrate that at different developmental stages of the brain, NG2(+) cells either stayed as NG2 glia or differentiated into OLs during the whole life span. Interestingly, when Cre activity was induced at embryonic stages, a significant number of reporter(+) astrocytes could be detected in the gray matter after birth. However, in other brain regions, such as olfactory bulb, brain stem, and cerebellum, all of the NG2 glia was restricted to the OL lineage. In addition, tamoxifen-sensitive and NG2 gene locus-dependent gene recombination could be detected in a small, but persistent population of cortical NeuN(+) neurons starting from the second postnatal week. PMID:24578301

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. 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)

  7. Effect of prenatal lead toxicity on surface ultrastructural features, elemental composition and infrared absorption characteristics of the skin of albino mice.

    PubMed

    Dey, S; Arjun, J; Das, M; Bhattacharjee, C R; Dkhar, P S

    2001-01-01

    The epidermis and dermis of albino mice born to females receiving oral sublethal doses of lead during pregnancy developed several abnormalities. These included perforations, tissue damage, cell deformity, and disordered organization of collagen bundles, as revealed by scanning electron microscopy. An increase in the concentrations of zinc, iron, magnesium, calcium and a decrease in that of copper was evident from atomic absorption spectroscopical analysis, when entire skin tissues were examined. Infrared spectroscopy revealed the occurrence of split bands in the spectra at 1,200-1,000 cm(-1), suggesting a reduction in the symmetry of the sulphate group (glycosaminoglycans) of skin probably caused by covalent bonding of it with lead. PMID:11545451

  8. 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. PMID:24583266

  9. 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)

  10. 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)

  11. 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)

  12. 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)

  13. 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)

  14. 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)

  15. 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)

  16. 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)

  17. 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)

  18. 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)

  19. 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)

  20. 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)

  1. 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)

  2. 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)

  3. 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)

  4. 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)

  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.

    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)

  7. 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)

  8. 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,…

  9. 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.…

  10. 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…

  11. 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.…

  12. 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)

  13. 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)

  14. 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)

  15. 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)

  16. 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…

  17. 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…

  18. Isolation, purification, and structural features of a polysaccharide from Phellinus linteus and its hypoglycemic effect in alloxan-induced diabetic mice.

    PubMed

    Zhao, Chao; Liao, Zunsheng; Wu, Xiaoqi; Liu, Yanling; Liu, Xiaoyan; Lin, Zhanxi; Huang, Yifan; Liu, Bin

    2014-05-01

    Phellinus linteus is a medicinal mushroom that has been used in Oriental countries for centuries for its antitumor, antioxidant, immunomodulatory, and biological activity on hyperglycemia. A water-soluble crude polysaccharide was extracted using hot water from P. linteus mycelia grown under submerged culture. An orthogonal experiment was used to optimize the extraction conditions of P. linteus mycelia polysaccharides (PLP). The crude polysaccharide was purified using DEAE Sephadex A-50 and Sephadex G-200 chromatography. Fourier transform infrared (FT-IR) spectroscopy and nuclear magnetic resonance ((1) H NMR) spectroscopy were used to investigate the structure of the purified P. linteus polysaccharide (PLP-I), revealing that it was mainly a branched-type glycan with both α- and β-linkages and a pyranoid sugar ring conformation. PLP orally administered at 100 mg/kg body weight/d could significantly reduce the blood glucose level by 35.60% in alloxan-induced diabetic mice. The results of an oral glucose tolerance test (OGTT) revealed that PLP had an effect on glucose disposal after 28 d of treatment. The result revealed that PLP from a submerged culture of P. linteus mycelia possessed potent hypoglycemic properties. The polysaccharide may be useful as a functional food additive and a hypoglycemic agent. PMID:24761950

  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 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

  20. 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)

  1. Kinetic Demonstration.

    ERIC Educational Resources Information Center

    Burgardt, Erik D.; Ryan, Hank

    1996-01-01

    Presents a unit on chemical reaction kinetics that consists of a predemonstration activity, the demonstration, and a set of postdemonstration activities that help students transfer the concepts to actual chemical reactions. Simulates various aspects of chemical reaction kinetics. (JRH)

  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

    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)

  4. 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)

  5. 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)

  6. 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)

  7. 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)

  8. 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)

  9. 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)

  10. 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

  11. Demonstration Explosion

    NASA Astrophysics Data System (ADS)

    Lee, Charles "Skip"

    1998-05-01

    Last week I did a demonstration that produced a serious explosion. After putting methanol in a big glass carboy and rotating the carboy to build up some methanol vapor, I lit the mouth of the carboy. What normally happens is a "jet engine" effect out of the mouth of the carboy. In my case, the carboy exploded. Two polycarbonate blast shields were shattered and glass was blown as far as 15 feet away. I was not seriously cut and bruised, but had I not been using the two blast shields, I would have been severely injured. At this time, I am not sure what caused the explosion. I have done this demonstration around one hundred times with no problem using the exact same amount of methanol and technique. I think it is important to get the word out that this demonstration may be more dangerous than previously thought. I would also welcome any hypotheses concerning what caused the carboy to explode.

  12. 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.…

  13. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1989-01-01

    Discusses three broad classes of magnetic behavior: diamagnetic, paramagnetic, and ferromagnetic. Presents a simple lecture demonstration using an overhead projector to synthesize triiron tetraoxide and to show its interaction with a magnetic field and comparing it to a paramagnetic material. (MVL)

  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

    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)

  16. 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)

  17. 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)

  18. 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)

  19. 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)

  20. 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)

  1. 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

  2. Progressive Neurodegeneration in Aspartylglycosaminuria Mice

    PubMed Central

    Gonzalez-Gomez, Ignacio; Mononen, Ilkka; Heisterkamp, Nora; Groffen, John; Kaartinen, Vesa

    1998-01-01

    Aspartylglycosaminuria (AGU) is one of the most common lysosomal storage disorders in humans. A mouse model for AGU has been recently generated through targeted disruption of the glycosylasparaginase gene, and at a young age the glycosyl asparaginase-deficient mice demonstrated many pathological changes found in human AGU patients (Kaartinen V, Mononen I, Voncken J-W, Gonzalez-Gomez I, Heisterkamp N, Groffen J: A mouse model for aspartylglycosaminuria. Nat Med 1996, 2:1375–1378). Our current findings demonstrate that after the age of 10 months, the general condition of null mutant mice gradually deteriorated. They suffered from a progressive motoric impairment and impaired bladder function and died prematurely. A widespread lysosomal hypertrophy in the central nervous system was detected. This neuronal vacuolation was particularly severe in the lateral thalamic nuclei, medullary reticular nuclei, vestibular nuclei, inferior olivary complex, and deep cerebellar nuclei. The oldest animals (20 months old) displayed a clear neuronal loss and gliosis, particularly in those regions, where the most severe vacuolation was found. The severe ataxic gait of the older mice was likely due to the dramatic loss of Purkinje cells, intensive astrogliosis and vacuolation of neurons in the deep cerebellar nuclei, and the severe vacuolation of the cells in vestibular and cochlear nuclei. The impaired bladder function and subsequent hydronephrosis were secondary to involvement of the central nervous system. These findings demonstrate that the glycosylasparaginase-deficient mice share many neuropathological features with human AGU patients, providing a suitable animal model to test therapeutic strategies in the treatment of the central nervous system effects in AGU. PMID:9777961

  3. 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.

  4. 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

  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. Immunopathogenesis of environmentally induced lupus in mice.

    PubMed

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

    1999-10-01

    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. PMID:10502537

  7. 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.

  8. Acoustic basis of directional acuity in laboratory mice.

    PubMed

    Lauer, Amanda M; Slee, Sean J; May, Bradford J

    2011-10-01

    The acoustic basis of auditory spatial acuity was investigated in CBA/129 mice by relating patterns of behavioral errors to directional features of the head-related transfer function (HRTF). Behavioral performance was assessed by training the mice to lick a water spout during sound presentations from a "safe" location and to suppress the response during presentations from "warning" locations. Minimum audible angles (MAAs) were determined by delivering the safe and warning sounds from different locations in the inter-aural horizontal and median vertical planes. HRTFs were measured at the same locations by implanting a miniature microphone and recording the gain of sound energy near the ear drum relative to free field. Mice produced an average MAA of 31° when sound sources were located in the horizontal plane. Acoustic measures indicated that binaural inter-aural level differences (ILDs) and monaural spectral features of the HRTF change systematically with horizontal location and therefore may have contributed to the accuracy of behavioral performance. Subsequent manipulations of the auditory stimuli and the directional properties of the ear produced errors that suggest the mice primarily relied on ILD cues when discriminating changes in azimuth. The MAA increased beyond 80° when the importance of ILD cues was minimized by testing in the median vertical plane. Although acoustic measures demonstrated a less robust effect of vertical location on spectral features of the HRTF, this poor performance provides further evidence for the insensitivity to spectral cues that was noted during behavioral testing in the horizontal plane. PMID:21717290

  9. A 7-month cigarette smoke inhalation study in C57BL/6 mice demonstrates reduced lung inflammation and emphysema following smoking cessation or aerosol exposure from a prototypic modified risk tobacco product.

    PubMed

    Phillips, Blaine; Veljkovic, Emilija; Peck, Michael J; Buettner, Ansgar; Elamin, Ashraf; Guedj, Emmanuel; Vuillaume, Gregory; Ivanov, Nikolai V; Martin, Florian; Boué, Stéphanie; Schlage, Walter K; Schneider, Thomas; Titz, Bjoern; Talikka, Marja; Vanscheeuwijck, Patrick; Hoeng, Julia; Peitsch, Manuel C

    2015-06-01

    Modified risk tobacco products (MRTP) are designed to reduce smoking-related health risks. A murine model of chronic obstructive pulmonary disease (COPD) was applied to investigate classical toxicology end points plus systems toxicology (transcriptomics and proteomics). C57BL/6 mice were exposed to conventional cigarette smoke (3R4F), fresh air (sham), or a prototypic MRTP (pMRTP) aerosol for up to 7 months, including a cessation group and a switching-to-pMRTP group (2 months of 3R4F exposure followed by fresh air or pMRTP for up to 5 months respectively). 3R4F smoke induced the typical adaptive changes in the airways, as well as inflammation in the lung, associated with emphysematous changes (impaired pulmonary function and alveolar damage). At nicotine-matched exposure concentrations of pMRTP aerosol, no signs of lung inflammation and emphysema were observed. Both the cessation and switching groups showed a similar reversal of inflammatory responses and no progression of initial emphysematous changes. A significant impact on biological processes, including COPD-related inflammation, apoptosis, and proliferation, was identified in 3R4F-exposed, but not in pMRTP-exposed lungs. Smoking cessation or switching reduced these perturbations to near sham-exposed levels. In conclusion, the mouse model indicated retarded disease progression upon cessation or switching to pMRTP which alone had no adverse effects. PMID:25843363

  10. Allergen-induced airway remodeling is impaired in galectin-3 deficient mice1

    PubMed Central

    Ge, Xiao Na; Bahaie, Nooshin S.; Kang, Bit Na; Hosseinkhani, Reza M.; Ha, Sung Gil; Frenzel, Elizabeth M.; Liu, Fu-Tong; Rao, Savita P.; Sriramarao, P.

    2010-01-01

    The role played by the β-galactoside-binding lectin galectin-3 (Gal-3) in airway remodeling, a characteristic feature of asthma that leads to airway dysfunction and poor clinical outcome in humans, was investigated in a murine model of chronic allergic airway inflammation. Wild-type (WT) and Gal-3 knock-out (KO) mice were subjected to repetitive allergen challenge with ovalbumin (OVA) up to 12 weeks and bronchoalveolar lavage fluid (BALF) and lung tissue collected after the last challenge were evaluated for cellular features associated with airway remodeling. Compared to WT mice, chronic OVA challenge in Gal-3 KO mice resulted in diminished remodeling of the airways with significantly reduced mucus secretion, sub-epithelial fibrosis, smooth muscle thickness, and peribronchial angiogenesis. The higher degree of airway remodeling in WT mice was associated with higher Gal-3 expression in the BALF as well as lung tissue. Cell counts in BALF and lung immunohistology demonstrated that eosinophil infiltration in OVA-challenged Gal-3 KO mice was significantly reduced compared to WT mice. Evaluation of cellular mediators associated with eosinophil recruitment and airway remodeling revealed that levels of eotaxin-1, IL-5, IL-13, FIZZ1 and TGF-β were substantially lower in Gal-3 KO mice. Finally, leukocytes from Gal-3 KO mice demonstrated decreased trafficking (rolling) on vascular endothelial adhesion molecules compared to WT cells. Overall, these studies demonstrate that Gal-3 is an important lectin that promotes airway remodeling via airway recruitment of inflammatory cells, specifically eosinophils, and the development of a Th2 phenotype as well as increased expression of eosinophil-specific chemokines, pro-fibrogenic and angiogenic mediators. PMID:20543100

  11. Space telerobotics technology demonstration program

    NASA Technical Reports Server (NTRS)

    Szirmay, S. Z.; Schenker, P. S.; Rodriguez, G.; French, R. L.

    1987-01-01

    The paper reports the ongoing development of a telerobot demonstrator. The demonstrator is implemented as a laboratory-based research testbed, and will show proof-of-concept for supervised automation of space assembly, servicing, and repair operations. The demonstrator system features a hierarchically layered intelligent control architecture which enables automated planning and run-time sequencing of complex tasks by a supervisory human operator. The demonstrator also provides a full bilateral force-reflecting hand control teleroperations capability. The operator may switch smoothly between the automated and teleroperated tasking modes in run-time, either on a preplanned or operator-designated basis.

  12. Deletion of IL-12p35 induces liver fibrosis in dominant negative transforming growth factor β receptor type II mice

    PubMed Central

    Tsuda, Masanobu; Zhang, Weici; Yang, Guo-Xiang; Tsuneyama, Koichi; Ando, Yugo; Kawata, Kazuhito; Park, Ogyi; Leung, Patrick S.C.; Coppel, Ross L.; Ansari, Aftab A.; Ridgway, William M.; Gao, Bin; Lian, Zhe-Xiong; Flavell, Richard; He, Xiao-Song; Gershwin, M. Eric

    2012-01-01

    We have previously reported that mice with a dominant negative transforming growth factor β receptor restricted to T cells (dnTGFβRII mice) develop an inflammatory biliary ductular disease that strongly resembles human primary biliary cirrhosis (PBC). Furthermore, deletion of the gene encoding interleukin (IL)-12p40 resulted in a strain (IL-12p40−/−dnTGFβRII) with dramatically reduced autoimmune cholangitis. To further investigate the role of the IL-12 cytokine family in dnTGFβRII autoimmune biliary disease, we deleted the gene encoding the IL-12p35 subunit from dnTGFβRII mice, resulting in an IL-12p35−/− dnTGFβRII strain which is deficient in two members of the IL-12 family, IL-12 and IL-35. In contrast to IL-12p40−/− mice, the IL-12p35−/− mice developed liver inflammation and bile duct damage with similar severity but delayed onset as the parental dnTGFβRII mice. The p35−/− mice also demonstrated a distinct cytokine profile characterized by a shift from a Th1 to a Th17 response. Strikingly, liver fibrosis was frequently observed in IL-12p35−/− mice. In conclusion, IL-12p35−/− dnTGFβRII mice, histologically and immunologically, reflect key features of PBC, providing a useful generic model to understand the immunopathology of human PBC. PMID:22576253

  13. 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.

  14. 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

  15. Adult sulfatide null mice maintain an increased number of oligodendrocytes

    PubMed Central

    Shroff, S; Pomicter, AD; Fox, MA; Henderson, SC; Dupree, JL

    2015-01-01

    The galactolipids galactocerebroside and sulfatide have been implicated in oligodendrocyte development and myelin formation. Much of the evidence for these galactolipid functions has been derived from antibody and chemical perturbation of cultured oligodendrocytes. Recently, we have observed abundant, unstable myelin and an increased number of oligodendrocytes in mice incapable of synthesizing the myelin galactolipids galactocerebroside and sulfatide. We have also reported that mice lacking sulfatide but that synthesize normal levels of galactocerebroside generate myelin with unstable paranodes while Hirahara et al. (2004) have shown an enhanced population of oligodendrocytes in the forebrain, medulla and cerebellum in immature sulfatide null mice. Here, we demonstrate that an increase in the number of oligodendrocytes in sulfatide null mice is not transient but is maintained through, at least, 7 months of age. Moreover, we demonstrate that the enhanced oligodendrocyte population results from, at least in part, increased cell survival. Finally, sulfatide null oligodendrocytes exhibit decreased morphological complexity, a feature which may relate to increased oligodendrocyte survival. PMID:19224580

  16. 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.

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

    PubMed Central

    Escobedo, Noelia; Proulx, Steven T.; Karaman, Sinem; Dillard, Miriam E.; Johnson, Nicole; Detmar, Michael; Oliver, Guillermo

    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

  18. 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

  19. The MICE Muon Beam Line

    SciTech Connect

    Apollonio, Marco

    2011-10-06

    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.

  20. Development of Social Vocalizations in Mice

    PubMed Central

    Grimsley, Jasmine M. S.; Monaghan, Jessica J. M.; Wenstrup, Jeffrey J.

    2011-01-01

    Adult mice are highly vocal animals, with both males and females vocalizing in same sex and cross sex social encounters. Mouse pups are also highly vocal, producing isolation vocalizations when they are cold or removed from the nest. This study examined patterns in the development of pup isolation vocalizations, and compared these to adult vocalizations. In three litters of CBA/CaJ mice, we recorded isolation vocalizations at ages postnatal day 5 (p5), p7, p9, p11, and p13. Adult vocalizations were obtained in a variety of social situations. Altogether, 28,384 discrete vocal signals were recorded using high-frequency-sensitive equipment and analyzed for syllable type, spectral and temporal features, and the temporal sequencing within bouts. We found that pups produced all but one of the 11 syllable types recorded from adults. The proportions of syllable types changed developmentally, but even the youngest pups produced complex syllables with frequency-time variations. When all syllable types were pooled together for analysis, changes in the peak frequency or the duration of syllables were small, although significant, from p5 through p13. However, individual syllable types showed different, large patterns of change over development, requiring analysis of each syllable type separately. Most adult syllables were substantially lower in frequency and shorter in duration. As pups aged, the complexity of vocal bouts increased, with a greater tendency to switch between syllable types. Vocal bouts from older animals, p13 and adult, had significantly more sequential structure than those from younger mice. Overall, these results demonstrate substantial changes in social vocalizations with age. Future studies are required to identify whether these changes result from developmental processes affecting the vocal tract or control of vocalization, or from vocal learning. To provide a tool for further research, we developed a MATLAB program that generates bouts of vocalizations

  1. 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)

  2. 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.

  3. 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)

  4. 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

  5. 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

  6. Knockout of Ste20-like proline/alanine-rich kinase (SPAK) attenuates intestinal inflammation in mice.

    PubMed

    Zhang, Yuchen; Viennois, Emilie; Xiao, Bo; Baker, Mark T; Yang, Stephen; Okoro, Ijeoma; Yan, Yutao

    2013-05-01

    Inflammatory bowel diseases are characterized by epithelial barrier disruption and alterations in immune regulation. Ste20-like proline/alanine-rich kinase (SPAK) plays a role in intestinal inflammation, but the underlying mechanisms need to be defined. Herein, SPAK knockout (KO) C57BL/6 mice exhibited significant increases in intestinal transepithelial resistance, a marked decrease in paracellular permeability to fluorescence isothiocyanate-dextran, and altered apical side tight junction sodium ion selectivity, compared with wild-type mice. Furthermore, the expression of junction protein, claudin-2, decreased. In contrast, expressions of occludin, E-cadherin, β-catenin, and claudin-5 increased significantly, whereas no obvious change of claudin-1, claudin-4, zonula occludens protein 1, and zonula occludens protein 2 expressions was observed. In murine models of colitis induced by dextran sulfate sodium and trinitrobenzene sulfuric acid, KO mice were more tolerant than wild-type mice, as demonstrated by colonoscopy features, histological characteristics, and myeloperoxidase activities. Consistent with these findings, KO mice showed increased IL-10 levels and decreased proinflammatory cytokine secretion, ameliorated bacterial translocation on treatment with dextran sulfate sodium, and regulation of with no lysine (WNK) kinase activity. Together, these features may reduce epithelial permeability. In conclusion, SPAK deficiency increases intestinal innate immune homeostasis, which is important for control or attenuation of pathological responses in inflammatory bowel diseases. PMID:23499375

  7. Exosomes from bronchoalveolar fluid of tolerized mice prevent allergic reaction.

    PubMed

    Prado, Noela; Marazuela, Eva G; Segura, Elodie; Fernández-García, Héctor; Villalba, Mayte; Théry, Clotilde; Rodríguez, Rosalía; Batanero, Eva

    2008-07-15

    Exosomes are nanovesicles originating from multivesicular bodies that are secreted by a variety of cell types. The dual capability of exosomes to promote immunity or to induce tolerance has prompted their clinical use as vehicles for vaccination against different human diseases. In the present study, the effect of allergen-specific exosomes from tolerized mice on the development of allergen-induced allergic response was determined using a mouse model. Mice were tolerized by respiratory exposure to the olive pollen allergen Ole e 1. Exosome-like vesicles were isolated from bronchoalveolar lavage fluid of the animals by the well-established filtration and ultracentrifugation procedure, characterized by electron microscopy, Western blot, and FACS analyses, and assessed in a prophylactic protocol. To this end, BALB/c mice were intranasally treated with tolerogenic exosomes or naive exosomes as control, 1 wk before sensitization/challenge to Ole e 1. Blood, lungs, and spleen were collected and analyzed for immune responses. Intranasal administration of tolerogenic exosomes inhibited the development of IgE response, Th2 cytokine production, and airway inflammation--cardinal features of allergy--and maintained specific long-term protection in vivo. This protective effect was associated with a concomitant increase in the expression of the regulatory cytokine TGF-beta. These observations demonstrate that exosomes can induce tolerance and protection against allergic sensitization in mice. Thus, exosome-based vaccines could represent an alternative to conventional therapy for allergic diseases in humans. PMID:18606707

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

    PubMed Central

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

    2014-01-01

    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 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 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 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. PMID:25236856

  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. PMID:25236856

  10. Maintenance of donor phenotype after full-thickness skin transplantation from mice with chronic proliferative dermatitis (cpdm/cpdm) to C57BL/Ka and nude mice and vice versa.

    PubMed

    Gijbels, M J; HogenEsch, H; Bruijnzeel, P L; Elliott, G R; Zurcher, C

    1995-12-01

    Chronic proliferative dermatitis is a spontaneous mutation in C57BL/Ka mice (cpdm/cpdm) and is characterized by epithelial hyperproliferation, infiltration by eosinophils and macrophages, and vascular dilatation. To elucidate whether these pathologic features are the result of a local (skin) process or a consequence of a systemic disorder, transplantations were performed of full-thickness grafts of affected skin from cpdm/cpdm mice and normal skin from control (C57BL/Ka) mice on the back of cpdm/cpdm, C57BL/Ka and athymic nude mice. After 3 months, the grafts maintained the histologic phenotype of the donor animal. Intercellular adhesion molecule-1 continued to be expressed by basal keratinocytes of the cpdm/cpdm grafts after transplantation. In contrast, the basal keratinocytes of the C57BL/Ka grafts onto cpdm/cpdm mice remained negative for intercellular adhesion molecule-1 3 months after transplantation. An increased number of proliferating keratinocytes was present in the cpdm/cpdm skin-graft transplanted to nudes or to C57BL/Ka mice based on short-term bromodeoxyuridine labeling. The bromodeoxyuridine incorporation in the keratinocytes of the control C57BL/Ka skin grafts transplanted to cpdm/cpdm, nude, or C57BL/Ka mice was the same as in the keratinocytes of normal C57BL/Ka mice. This study demonstrates that the pathologic features found in the cpdm/cpdm mice are the result of a disorder in the epidermis or dermis and not due to a systemic defect. PMID:7490470

  11. 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.

  12. 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

  13. 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. PMID:24742627

  14. MICE Staging and Status

    SciTech Connect

    Hanlet, Pierrick

    2010-03-30

    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 approx2012.

  15. 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.

  16. 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.

  17. Thymic epithelium determines a spontaneous chronic neuritis in Icam1(tm1Jcgr)NOD mice.

    PubMed

    Meyer zu Horste, Gerd; Mausberg, Anne K; Cordes, Steffen; El-Haddad, Houda; Partke, Hans-Joachim; Leussink, Verena I; Roden, Michael; Martin, Stephan; Steinman, Lawrence; Hartung, Hans-Peter; Kieseier, Bernd C

    2014-09-15

    The NOD mouse strain spontaneously develops autoimmune diabetes. A deficiency in costimulatory molecules, such as B7-2, on the NOD genetic background prevents diabetes but instead triggers an inflammatory peripheral neuropathy. This constitutes a shift in the target of autoimmunity, but the underlying mechanism remains unknown. In this study, we demonstrate that NOD mice deficient for isoforms of ICAM-1, which comediate costimulatory functions, spontaneously develop a chronic autoimmune peripheral neuritis instead of diabetes. The disease is transferred by CD4(+) T cells, which infiltrate peripheral nerves together with macrophages and B cells and are autoreactive against peripheral myelin protein zero. These Icam1(tm1Jcgr)NOD mice exhibit unaltered numbers of regulatory T cells, but increased IL-17-producing T cells, which determine the severity, but not the target specificity, of autoimmunity. Ab-mediated ICAM-1 blockade triggers neuritis only in young NOD mice. Thymic epithelium from Icam1(tm1Jcgr)NOD mice features an altered expression of costimulatory molecules and induces neuritis and myelin autoreactivity after transplantation into nude mice in vivo. Icam1(tm1Jcgr)NOD mice exhibit a specifically altered TCR repertoire. Our findings introduce a novel animal model of chronic inflammatory neuropathies and indicate that altered expression of ICAM-1 on thymic epithelium shifts autoimmunity specifically toward peripheral nerves. This improves our understanding of autoimmunity in the peripheral nervous system with potential relevance for human diseases. PMID:25108020

  18. 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)

  19. 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)

  20. Classical Demonstration of Polarization.

    ERIC Educational Resources Information Center

    Bauman, Robert P.; Moore, Dennis R.

    1980-01-01

    Presents a classical demonstration of polarization for high school students. The initial state of this model, which demonstrates the important concepts of the optical and quantum problems, was developed during the 1973 summer program on lecture demonstration at the U.S. Naval Academy. (HM)

  1. 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)

  2. 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)

  3. Enhanced Susceptibility to Pulmonary Infection with Burkholderia cepacia in Cftr−/− Mice

    PubMed Central

    Sajjan, Uma; Thanassoulis, George; Cherapanov, Vera; Lu, Annie; Sjolin, Carola; Steer, Brent; Wu, Yi Jun; Rotstein, Ori D.; Kent, Geraldine; McKerlie, Colin; Forstner, Janet; Downey, Gregory P.

    2001-01-01

    Progressive pulmonary infection is the dominant clinical feature of cystic fibrosis (CF), but the molecular basis for this susceptibility remains incompletely understood. To study this problem, we developed a model of chronic pneumonia by repeated instillation of a clinical isolate of Burkholderia cepacia (genomovar III, ET12 strain), an opportunistic gram-negative bacterium, from a case of CF into the lungs of Cftr m1unc−/− (Cftr−/−) and congenic Cftr+/+ controls. Nine days after the last instillation, the CF transmembrane regulator knockout mice showed persistence of viable bacteria with chronic severe bronchopneumonia while wild-type mice remained healthy. The histopathological changes in the lungs of the susceptible Cftr−/− mice were characterized by infiltration of a mixed inflammatory-cell population into the peribronchiolar and perivascular spaces, Clara cell hyperplasia, mucus hypersecretion in airways, and exudation into alveolar airspaces by a mixed population of macrophages and neutrophils. An increased proportion of neutrophils was observed in bronchoalveolar lavage fluid from the Cftr−/− mice, which, despite an increased bacterial load, demonstrated minimal evidence of activation. Alveolar macrophages from Cftr−/− mice also demonstrated suboptimal activation. These observations suggest that the pulmonary host defenses are compromised in lungs from animals with CF, as manifested by increased susceptibility to bacterial infection and lung injury. This murine model of chronic pneumonia thus reflects, in part, the situation in human patients and may help elucidate the mechanisms leading to defective host defense in CF. PMID:11447196

  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. 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.

  6. 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.

  7. Data surety demonstrations

    SciTech Connect

    Draelos, T.; Harris, M.; Herrington, P.; Kromer, D.

    1998-08-01

    The use of data surety within the International Monitoring System (IMS) is designed to offer increased trust of acquired sensor data at a low cost. The demonstrations discussed in the paper illustrate the feasibility of hardware authentication for sensor data and commands in a retrofit environment and a new system and of the supporting key management system. The individual demonstrations which are summarized in the paper are: (1) demonstration of hardware authentication for communication authentication in a retrofit environment; (2)demonstration of hardware authentication in a new system; and (3) demonstration of key management for sensor data and command authentication.

  8. 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

  9. 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

  10. The Microgravity Demonstrator

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

    The Demonstrator is a tool to create microgravity conditions in your classroom. A series of demonstrations is used to provide a dramatically visual, physical connection between free-fall and microgravity conditions and to understand why various types of experiments are performed under microgravity conditions. A wealth of back-round material on free-fall, microgravity, and micro-gravity sciences is available in two educational documents available through the NASA Teacher Resource Centers: Microgravity-Activity Guide for Science, Mathematics, and Technology Education, and The Mathematics of Microgravity. The remainder of this manual is divided into five sections. The first explains how to put the Microgravity Demonstrator together. The next section introduces the individual demonstrations and discusses the underlying physical science concepts. Following that are detailed steps for conducting each demonstration to make your use of the Demonstrator most effective. Next are some ideas on how to make your own Microgravity Demonstrator. The last section is a tips and troubleshooting guide for video connections and operations. If you have one of the NASA Microgravity Demonstrators, this entire manual should be useful. If you have a copy of the Microgravity Demonstrator Videotape and would like to use that as a teaching tool, the Demonstrations and Scientific Background section of this manual will give you insight into the science areas studied in microgravity.

  11. Helicopter detection and classification demonstrator

    NASA Astrophysics Data System (ADS)

    van Koersel, Antonius C.

    2000-07-01

    A technology demonstrator that detects and classifies different helicopter types automatically, was developed at TNO-FEL. The demonstrator is based on a PC, which receives its acoustic input from an all-weather microphone. The demonstrator uses commercial off-the-shelf hardware to digitize the acoustic signal. The user-interface and the signal processing software are written in MatLabTM. The demonstrator detects the noise from helicopters; the classification is performed using a database with helicopter-specific features. The demonstrator currently contains information of 11 different helicopter types, but can easily be expanded to include additional types of helicopters. The input signal is analyzed in real time, the result is a classification ranging from `no target' to `helicopter type x', e.g. Lynx Mk2. If the helicopter is classified, its relative speed is estimated as well. The algorithm was developed and tested using a database of different helicopters (hovering and moving) recorded at distances ranging from 90 meter up to 8 kilometer. The sensitivity to noise was investigated using jet, tank, artillery and environmental (wind and turbulence) noise as input.

  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. 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....

  14. 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.

  15. 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.

  16. 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.

  17. 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…

  18. Dental and Cranial Pathologies in Mice Lacking the Cl(-) /H(+) -Exchanger ClC-7.

    PubMed

    Wen, Xin; Lacruz, Rodrigo S; Paine, Michael L

    2015-08-01

    ClC-7 is a 2Cl(-) /1H(+) -exchanger expressed at late endosomes and lysosomes, as well as the ruffled border of osteoclasts. ClC-7 deficiencies in mice and humans lead to impaired osteoclast function and therefore osteopetrosis. Failure of tooth eruption is also apparent in ClC-7 mutant animals, and this has been attributed to the osteoclast dysfunction and the subsequent defect in alveolar bone resorptive activity surrounding tooth roots. Ameloblasts also express ClC-7, and this study aims to determine the significance of ClC-7 in enamel formation by examining the dentitions of ClC-7 mutant mice. Micro-CT analysis revealed that the molar teeth of 3-week old ClC-7 mutant mice had no roots, and the incisors were smaller than their age-matched controls. Despite these notable developmental differences, the enamel and dentin densities of the mutant mice were comparable to those of the wild-type littermates. Scanning electron microscopy showed normal enamel crystallite and prismatic organization in the ClC-7 mutant mice, although the enamel was thinner (hypoplastic) than in controls. These results suggested that ClC-7 was not critical to enamel and dentin formation, and the observed tooth defects may be related more to a resulting alveolar bone phenotype. Micro-CT analysis also revealed abnormal features in the calvarial bones of the mutant mice. The cranial sutures in ClC-7 mutant mice remained open compared to the closed sutures seen in the control mice at 3 weeks. These data demonstrate that ClC-7 deficiency impacts the development of the dentition and calvaria, but does not significantly disrupt amelogenesis. PMID:25663454

  19. 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)

  20. 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.

  1. Targeted inactivation of the mouse locus encoding coagulation factor XIII-A: hemostatic abnormalities in mutant mice and characterization of the coagulation deficit.

    PubMed

    Lauer, Peter; Metzner, Hubert J; Zettlmeissl, Gerd; Li, Meng; Smith, Austin G; Lathe, Richard; Dickneite, Gerhard

    2002-12-01

    Blood coagulation factor XIII (FXIII) promotes cross-linking of fibrin during blood coagulation; impaired clot stabilization in human genetic deficiency is associated with marked pathologies of major clinical impact, including bleeding symptoms and deficient wound healing. To investigate the role of FXIII we employed homologous recombination to generate a targeted deletion of the inferred exon 7 of the FXIII-A gene. FXIII transglutaminase activity in plasma was reduced to about 50% in mice heterozygous for the mutant allele, and was abolished in homozygous null mice. Plasma fibrin gamma-dimerization was also indetectable in the homozygous deficient animals, confirming the absence of activatable FXIII. Homozygous mutant mice were fertile, although reproduction was impaired. Bleeding episodes, hematothorax, hematoperitoneum and subcutaneous hemorrhage in mutant mice were associated with reduced survival. Arrest of tail-tip bleeding in FXIII-A deficient mice was markedly and significantly delayed; replacement of mutant mice with human plasma FXIII (Fibrogammin P) restored bleeding time to within the normal range. Thrombelastography (TEG) experiments demonstrated impaired clot stabilization in FXIII-A mutant mice, replacement with human FXIII led to dose-dependent TEG normalization. The mutant mice thus reiterate some key features of the human genetic disorder: they will be valuable in assessing the role of FXIII in other associated pathologies and the development of new therapies. PMID:12529747

  2. 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)

  3. 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…

  4. 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)

  5. 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…

  6. 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…

  7. Demonstrating Reduced Gravity.

    ERIC Educational Resources Information Center

    Pearlman, Howard; And Others

    1996-01-01

    Describes the construction of the Reduced-Gravity Demonstrator, which can be used to illustrate the effects of gravity on a variety of phenomena, including the way fluids flow, flames burn, and mechanical systems behave. Presents experiments, appropriate for classroom use, to demonstrate how the behavior of common physical systems change when…

  8. 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.

  9. 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…

  10. 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…

  11. 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)

  12. 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.

  13. Demonstrating environmental compliance

    SciTech Connect

    Pankratz, R.H.

    1995-12-31

    Almost every company, plant, or government entity wants to be in compliance with environmental statutes, regulations, and permit provisions. Today wanting is not enough. At the Pantex Plant, we have taken the approach, that unless we can demonstrate compliance, we are not necessarily in compliance. This paper is intended to illustrate how the Pantex Plant has designed its various programs to demonstrate compliance with environmental statutes, regulations, and permit provisions. A major emphasis is to have permit provisions that are objective and measurable so as to aid in demonstrating compliance. In conjunction with unambiguous permit provisions, appropriate management systems are required to provide the necessary records for this documentation.

  14. Innovative technology demonstration

    SciTech Connect

    Anderson, D.B.; Luttrell, S.P.; Hartley, J.N.; Hinchee, R.

    1992-04-01

    The Innovative Technology Demonstration (ITD) program at Tinker Air Force Base (TAFB), Oklahoma City, Oklahoma, will demonstrate the overall utility and effectiveness of innovative technologies for site characterization, monitoring, and remediation of selected contaminated test sites. The current demonstration test sites include a CERCLA site on the NPL list, located under a building (Building 3001) that houses a large active industrial complex used for rebuilding military aircraft, and a site beneath and surrounding an abandoned underground tank vault used for storage of jet fuels and solvents. The site under Building 3001 (the NW Test Site) is contaminated with TCE and Cr{sup {plus}6}; the site with the fuel storage vault (the SW Tanks Site) is contaminated with fuels, BTEX and TCE. These sites and others have been identified for cleanup under the Air Force`s Installation Restoration Program (IRP). This document describes the demonstrations that have been conducted or are planned for the TAFB.

  15. Innovative technology demonstration

    SciTech Connect

    Anderson, D.B.; Luttrell, S.P. ); Hartley, J.N. ); Hinchee, R. )

    1992-04-01

    The Innovative Technology Demonstration (ITD) program at Tinker Air Force Base (TAFB), Oklahoma City, Oklahoma, will demonstrate the overall utility and effectiveness of innovative technologies for site characterization, monitoring, and remediation of selected contaminated test sites. The current demonstration test sites include a CERCLA site on the NPL list, located under a building (Building 3001) that houses a large active industrial complex used for rebuilding military aircraft, and a site beneath and surrounding an abandoned underground tank vault used for storage of jet fuels and solvents. The site under Building 3001 (the NW Test Site) is contaminated with TCE and Cr{sup {plus}6}; the site with the fuel storage vault (the SW Tanks Site) is contaminated with fuels, BTEX and TCE. These sites and others have been identified for cleanup under the Air Force's Installation Restoration Program (IRP). This document describes the demonstrations that have been conducted or are planned for the TAFB.

  16. 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)

  17. 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.

  18. 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)

  19. 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)

  20. 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.

  1. 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.

  2. 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.

  3. 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....

  4. 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...

  5. 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)

  6. 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)

  7. 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.

  8. 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)

  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. Dexterous manipulator flight demonstration

    NASA Technical Reports Server (NTRS)

    Carter, Edward L.

    1989-01-01

    The Dexterous Manipulator Flight Experiment, an outgrowth of the Dexterous End Effector project, is an experiment to demonstrate newly developed equipment and methods that make for a dexterous manipulator which can be used on the Space Shuttle or other space missions. The goals of the project, the objectives of the flight experiment, the experiment equipment, and the tasks to be performed during the demonstration are discussed.

  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. Long term effects of high fat or high carbohydrate diets on glucose tolerance in mice with heterozygous carnitine palmitoyltransferase-1a (CPT-1a) deficiency: Diet influences on CPT1a deficient mice.

    PubMed

    Nyman, Lara R; Tian, Liqun; Hamm, Doug A; Schoeb, Trenton R; Gower, Barbara A; Nagy, Tim R; Wood, Philip A

    2011-08-22

    BACKGROUND: Abnormal fatty acid metabolism is an important feature in the mechanisms of insulin resistance and beta-cell dysfunction. Carnitine palmitoyltransferase-1a (CPT-1a, liver isoform) plays a pivotal role in the regulation of mitochondrial fatty acid oxidation. We investigated the role of CPT-1a in the development of impaired glucose tolerance using a mouse model for CPT-1a deficiency when challenged by either a high-carbohydrate (HCD) or a high-fat diet (HFD) for a total duration of up to 46 weeks. METHODS: Insulin sensitivity and glucose tolerance were assessed in heterozygous CPT-1a deficient (CPT-1a+/-) male mice after being fed either a HCD or a HFD for durations of 28 weeks and 46 weeks. Both glucose and insulin tolerance tests were used to investigate beta-cell function and insulin sensitivity. Differences in islet insulin content and hepatic steatosis were evaluated by morphological analysis. RESULTS: CPT-1a+/- mice were more insulin sensitive than CPT-1a+/+ mice when fed either HCD or HFD. The increased insulin sensitivity was associated with an increased expression of Cpt-1b (muscle isoform) in liver, as well as increased microvesicular hepatic steatosis compared to CPT-1a+/+ mice. CPT-1a+/- mice were more glucose tolerant than CPT-1a+/+ mice when fed the HCD, but there was no significant difference when fed HFD. Moreover, CPT-1a+/- mice fed HFD or HCD had fewer and smaller pancreatic islets than CPT-1a+/+ mice. CONCLUSIONS: CPT-1a deficiency preserved insulin sensitivity when challenged by long term feeding of either diet. Furthermore, CPT-1a deficient mice had distinct phenotypes dependent on the diet fed demonstrating that both diet and genetics collectively play a role in the development of impaired glucose tolerance. PMID:22229081

  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. 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

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

    PubMed

    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

  16. 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

  17. Characterization of Sleeping Beauty Transposition and Its Application to Genetic Screening in Mice

    PubMed Central

    Horie, Kyoji; Yusa, Kosuke; Yae, Kojiro; Odajima, Junko; Fischer, Sylvia E. J.; Keng, Vincent W.; Hayakawa, Tomoko; Mizuno, Sumi; Kondoh, Gen; Ijiri, Takashi; Matsuda, Yoichi; Plasterk, Ronald H. A.; Takeda, Junji

    2003-01-01

    The use of mutant mice plays a pivotal role in determining the function of genes, and the recently reported germ line transposition of the Sleeping Beauty (SB) transposon would provide a novel system to facilitate this approach. In this study, we characterized SB transposition in the mouse germ line and assessed its potential for generating mutant mice. Transposition sites not only were clustered within 3 Mb near the donor site but also were widely distributed outside this cluster, indicating that the SB transposon can be utilized for both region-specific and genome-wide mutagenesis. The complexity of transposition sites in the germ line was high enough for large-scale generation of mutant mice. Based on these initial results, we conducted germ line mutagenesis by using a gene trap scheme, and the use of a green fluorescent protein reporter made it possible to select for mutant mice rapidly and noninvasively. Interestingly, mice with mutations in the same gene, each with a different insertion site, were obtained by local transposition events, demonstrating the feasibility of the SB transposon system for region-specific mutagenesis. Our results indicate that the SB transposon system has unique features that complement other mutagenesis approaches. PMID:14645530

  18. 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

  19. 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

  20. 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

  1. Pneumonitis and emphysema in sp-C gene targeted mice.

    PubMed

    Glasser, Stephan W; Detmer, Emily A; Ikegami, Machiko; Na, Cheng-Lun; Stahlman, Mildred T; Whitsett, Jeffrey A

    2003-04-18

    SP-C-deficient (SP-C -/-) mice developed a severe pulmonary disorder associated with emphysema, monocytic infiltrates, epithelial cell dysplasia, and atypical accumulations of intracellular lipids in type II epithelial cells and alveolar macrophages. Whereas alveolar and tissue surfactant phospholipid pools were increased, levels of other surfactant proteins were not altered (SP-B) or were modestly increased (SP-A and SP-D). Analysis of pressure-volume curves and forced oscillatory dynamics demonstrated abnormal respiratory mechanics typical of emphysema. Lung disease was progressive, causing weight loss and cardiomegaly. Extensive alveolar remodeling was accompanied by type II cell hyperplasia, obliteration of pulmonary capillaries, and widespread expression of alpha-smooth muscle actin, indicating myofibroblast transformation in the lung parenchyma. Dysplastic epithelial cells lining conducting airways stained intensely for the mucin, MUC5A/C. Tissue concentrations of proinflammatory cytokines were not substantially altered in the SP-C (-/-) mice. Production of matrix metalloproteinases (MMP-2 and MMP-9) was increased in alveolar macrophages from SP-C (-/-) mice. Absence of SP-C caused a severe progressive pulmonary disorder with histologic features consistent with interstitial pneumonitis. PMID:12519727

  2. 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.

  3. Autonomous docking ground demonstration

    NASA Technical Reports Server (NTRS)

    Lamkin, Steve L.; Le, Thomas Quan; Othon, L. T.; Prather, Joseph L.; Eick, Richard E.; Baxter, Jim M.; Boyd, M. G.; Clark, Fred D.; Spehar, Peter T.; Teters, Rebecca T.

    1991-01-01

    The Autonomous Docking Ground Demonstration is an evaluation of the laser sensor system to support the docking phase (12 ft to contact) when operated in conjunction with the guidance, navigation, and control (GN&C) software. The docking mechanism being used was developed for the Apollo/Soyuz Test Program. This demonstration will be conducted using the 6-DOF Dynamic Test System (DTS). The DTS simulates the Space Station Freedom as the stationary or target vehicle and the Orbiter as the active or chase vehicle. For this demonstration, the laser sensor will be mounted on the target vehicle and the retroflectors will be on the chase vehicle. This arrangement was chosen to prevent potential damage to the laser. The laser sensor system, GN&C, and 6-DOF DTS will be operated closed-loop. Initial conditions to simulate vehicle misalignments, translational and rotational, will be introduced within the constraints of the systems involved.

  4. 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.

  5. Innovative technology demonstrations

    SciTech Connect

    Anderson, D.B.; Luttrell, S.P. ); Hartley, J.N. . Environmental Management Operations); Hinchee, R. )

    1992-08-01

    Environmental Management Operations (EMO) is conducting an Innovative Technology Demonstration Program for Tinker Air Force Base (TAFB). Several innovative technologies are being demonstrated to address specific problems associated with remediating two contaminated test sites at the base. Cone penetrometer testing (CPT) is a form of testing that can rapidly characterize a site. This technology was selected to evaluate its applicability in the tight clay soils and consolidated sandstone sediments found at TAFB. Directionally drilled horizontal wells was selected as a method that may be effective in accessing contamination beneath Building 3001 without disrupting the mission of the building, and in enhancing the extraction of contamination both in ground water and in soil. A soil gas extraction (SGE) demonstration, also known as soil vapor extraction, will evaluate the effectiveness of SGE in remediating fuels and TCE contamination contained in the tight clay soil formations surrounding the abandoned underground fuel storage vault located at the SW Tanks Site. In situ sensors have recently received much acclaim as a technology that can be effective in remediating hazardous waste sites. Sensors can be useful for determining real-time, in situ contaminant concentrations during the remediation process for performance monitoring and in providing feedback for controlling the remediation process. Following the SGE demonstration, the SGE system and SW Tanks test site will be modified to demonstrate bioremediation as an effective means of degrading the remaining contaminants in situ. The bioremediation demonstration will evaluate a bioventing process in which the naturally occurring consortium of soil bacteria will be stimulated to aerobically degrade soil contaminants, including fuel and TCE, in situ.

  6. Innovative technology demonstrations

    SciTech Connect

    Anderson, D.B.; Hartley, J.N.; Luttrell, S.P.

    1992-04-01

    Currently, several innovative technologies are being demonstrated at Tinker Air Force Base (TAFB) to address specific problems associated with remediating two contaminated test sites at the base. Cone penetrometer testing (CPT) is a form of testing that can rapidly characterize a site. This technology was selected to evaluate its applicability in the tight clay soils and consolidated sandstone sediments found at TAFB. Directionally drilled horizontal wells have been successfully installed at the US Department of Energy's (DOE) Savannah River Site to test new methods of in situ remediation of soils and ground water. This emerging technology was selected as a method that may be effective in accessing contamination beneath Building 3001 without disrupting the mission of the building, and in enhancing the extraction of contamination both in ground water and in soil. A soil gas extraction (SGE) demonstration, also known as soil vapor extraction, will evaluate the effectiveness of SGE in remediating fuels and TCE contamination contained in the tight clay soil formations surrounding the abandoned underground fuel storage vault located at the SW Tanks Site. In situ sensors have recently received much acclaim as a technology that can be effective in remediating hazardous waste sites. Sensors can be useful for determining real-time, in situ contaminant concentrations during the remediation process for performance monitoring and in providing feedback for controlling the remediation process. A demonstration of two in situ sensor systems capable of providing real-time data on contamination levels will be conducted and evaluated concurrently with the SGE demonstration activities. Following the SGE demonstration, the SGE system and SW Tanks test site will be modified to demonstrate bioremediation as an effective means of degrading the remaining contaminants in situ.

  7. Innovative technology demonstrations

    SciTech Connect

    Anderson, D.B.; Hartley, J.N.; Luttrell, S.P.

    1992-04-01

    Currently, several innovative technologies are being demonstrated at Tinker Air Force Base (TAFB) to address specific problems associated with remediating two contaminated test sites at the base. Cone penetrometer testing (CPT) is a form of testing that can rapidly characterize a site. This technology was selected to evaluate its applicability in the tight clay soils and consolidated sandstone sediments found at TAFB. Directionally drilled horizontal wells have been successfully installed at the US Department of Energy`s (DOE) Savannah River Site to test new methods of in situ remediation of soils and ground water. This emerging technology was selected as a method that may be effective in accessing contamination beneath Building 3001 without disrupting the mission of the building, and in enhancing the extraction of contamination both in ground water and in soil. A soil gas extraction (SGE) demonstration, also known as soil vapor extraction, will evaluate the effectiveness of SGE in remediating fuels and TCE contamination contained in the tight clay soil formations surrounding the abandoned underground fuel storage vault located at the SW Tanks Site. In situ sensors have recently received much acclaim as a technology that can be effective in remediating hazardous waste sites. Sensors can be useful for determining real-time, in situ contaminant concentrations during the remediation process for performance monitoring and in providing feedback for controlling the remediation process. A demonstration of two in situ sensor systems capable of providing real-time data on contamination levels will be conducted and evaluated concurrently with the SGE demonstration activities. Following the SGE demonstration, the SGE system and SW Tanks test site will be modified to demonstrate bioremediation as an effective means of degrading the remaining contaminants in situ.

  8. 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.

  9. 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. PMID:19064476

  10. 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.

  11. Zinc metabolism in genetically obese mice

    SciTech Connect

    Kennedy, M.L.; Failla, M.L.

    1986-03-05

    Recent reports indicate that the concentrations and total amounts of several essential trace metals in various tissues of genetically obese rodents differ markedly from lean controls. In the present studies the absorption, retention and tissue distribution of zinc was compared in obese (ob/ob) and lean (+/.) C57BL/6J mice. When administered 0.1 and 1 umole /sup 65/Zn by stomach tube and killed after 4 h, fasted 10 week old obese mice had 2.7 and 2.2 times more radioactivity in their carcasses, respectively, than age-matched lean mice. Higher levels of /sup 65/Zn were also present in the intestinal mucosa of obese mice. To eliminate possible differences in the effects of fasting and gastric emptying rates between the phenotypes, zinc absorption and retention were determined according to the method of Heth and Hoekstra. Analysis of data revealed that obese and lean mice absorbed 43 and 18% of the oral dose, respectively. Also, the rate of /sup 65/Zn excretion between 2 and 6 days post-treatment was similar for obese and lean mice. After 6 days obese mice had significantly lower levels of radioisotope in skin, muscle plus bone, spleen and testes and higher levels of /sup 65/Zn in liver, small intestine and adipose tissue compared to tissues from lean mice. These results demonstrate increased absorption, altered tissue distribution and similar excretion of zinc in ob/ob mice.

  12. 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

  13. Features of Positive Developmental Settings

    ERIC Educational Resources Information Center

    Larson, Reed; Eccles, Jacquelynne; Gootman, Jennifer Appleton

    2004-01-01

    There is very little research that directly specifies what programs can do to facilitate positive adolescent development, or how to tailor these programs to the individual needs of adolescents. However, there is a broad base of knowledge about how development occurs that can be drawn upon. Research demonstrates that certain features of the…

  14. Cholinergic influences on feature binding.

    PubMed

    Botly, Leigh C P; De Rosa, Eve

    2007-04-01

    The binding problem refers to the fundamental challenge of the central nervous system to integrate sensory information registered by multiple brain regions to form a unified neural representation of a stimulus. Human behavioral, neuropsychological, and functional neuroimaging evidence suggests a fundamental role for attention in feature binding; however, its neurochemical basis is currently unknown. This study examined whether acetylcholine (ACh), a neuromodulator that has been implicated in attentional processes, plays a critical role in feature binding. Using a within-subjects pharmacological design and the cholinergic muscarinic antagonist scopolamine, the present experiments demonstrate, in a rat model, a critical role for the cortical muscarinic cholinergic system in feature binding. Specifically, ACh and the attentional resources that it supports are essential for the initial feature binding process but are not required to maintain neural representations of bound stimuli. PMID:17469916

  15. Space fabrication demonstration system

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The lower right aluminum beam cap roll forming mill was delivered and installed in the beam builder. The beam was brought to full operational status and beams of one to six bay lengths were produced to demonstrate full system capability. Although the cap flange waviness problem persists, work is progressing within cost and schedule.

  16. 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)

  17. 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.…

  18. ALASKA VILLAGE DEMONSTRATION PROJECTS

    EPA Science Inventory

    Two demonstration projects were built as authorized by Section 113 of PL 92-500. Modular construction was used to provide central utility systems which included water supply, laundry, bathing, saunas, and wastewater treatment. Service to homes was by vehicular delivery. Fire dest...

  19. 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.…

  20. Musical acoustics demonstrations

    NASA Astrophysics Data System (ADS)

    Hoekje, P. L.

    2003-10-01

    The ASA Musical Acoustics Demonstrations website (trial version at http://www.bw.edu/~phoekje) includes sound files, video clips, program code listings, and other material for demonstrations related to musical acoustics. Many of the sound demonstrations may be experienced either as expositions, in which the phenomena are explained before they are presented, or as experiments, in which the explanation comes after listeners have had the opportunity to draw their own conclusions. Suggestions are provided for apparatus construction and classroom experiments, as well as for building simple musical instruments. Software is recommended if it is available free and compatible with multiple personal computer operating systems. For example, Audacity (http://audacity.sourceforce.net) is a sound file editor and analyzer that can be used to visually represent sounds and manipulate them. Source files are included for the synthesized sound examples, which were created in Csound (http://csounds.com), so that interested users may create their own variations. Source code is also included for visual demonstrations created in Visual Python and Python (http://www.python.org), an efficient, high level programming language. Suggestions, criticisms, and contributions are always welcome! [Work supported by ASA and Baldwin-Wallace College.

  1. Polarized Light: Three Demonstrations.

    ERIC Educational Resources Information Center

    Goehmann, Ruth; Welty, Scott

    1984-01-01

    Describes three demonstrations used in the Chicago Museum of Science and Industry polarized light show. The procedures employed are suitable for the classroom by using smaller polarizers and an overhead projector. Topic areas include properties of cellophane tape, nondisappearing arrows, and rope through a picket fence. (JN)

  2. Astronomy LITE Demonstrations

    NASA Astrophysics Data System (ADS)

    Brecher, Kenneth

    2006-12-01

    Project LITE (Light Inquiry Through Experiments) is a materials, software, and curriculum development project. It focuses on light, optics, color and visual perception. According to two recent surveys of college astronomy faculty members, these are among the topics most often included in the large introductory astronomy courses. The project has aimed largely at the design and implementation of hands-on experiences for students. However, it has also included the development of lecture demonstrations that employ novel light sources and materials. In this presentation, we will show some of our new lecture demonstrations concerning geometrical and physical optics, fluorescence, phosphorescence and polarization. We have developed over 200 Flash and Java applets that can be used either by teachers in lecture settings or by students at home. They are all posted on the web at http://lite.bu.edu. For either purpose they can be downloaded directly to the user's computer or run off line. In lecture demonstrations, some of these applets can be used to control the light emitted by video projectors to produce physical effects in materials (e.g. fluorescence). Other applets can be used, for example, to demonstrate that the human percept of color does not have a simple relationship with the physical frequency of the stimulating source of light. Project LITE is supported by Grant #DUE-0125992 from the NSF Division of Undergraduate Education.

  3. SOIL BIOVENTING DEMONSTRATION PROJECT

    EPA Science Inventory

    A pilot scale demonstration project of a soil bioventing system, which utilizes the biodegradation in soil and physical removal of VOC by induced air flow, is in operation at the U.S. Coast Guard Aviation Field in Traverse City, Michigan. he system is being tested to determine it...

  4. 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)

  5. 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,…

  6. 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)

  7. 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)

  8. More Diamagnetism Demonstrations

    NASA Astrophysics Data System (ADS)

    Conery, Chris; Goodrich, L. F.; Stauffer, T. C.

    2003-02-01

    Inspired by, among others, Charles Sawicki's description of an inexpensive diamagnetic levitation apparatus, we built two such devices for classroom use and for educational outreach at the National Institute of Standards and Technology, Boulder, Colo. With a slightly different setup, the same demonstration can be done horizontally on an overhead projector.

  9. 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…

  10. 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…

  11. 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.

  12. 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,…

  13. 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…

  14. OPG-Fc but Not Zoledronic Acid Discontinuation Reverses Osteonecrosis of the Jaws (ONJ) in Mice.

    PubMed

    de Molon, Rafael Scaf; Shimamoto, Hiroaki; Bezouglaia, Olga; Pirih, Flavia Q; Dry, Sarah M; Kostenuik, Paul; Boyce, Rogely W; Dwyer, Denise; Aghaloo, Tara L; Tetradis, Sotirios

    2015-09-01

    Osteonecrosis of the jaws (ONJ) is a significant complication of antiresorptive medications, such as bisphosphonates and denosumab. Antiresorptive discontinuation to promote healing of ONJ lesions remains highly controversial and understudied. Here, we investigated whether antiresorptive discontinuation alters ONJ features in mice, employing the potent bisphosphonate zoledronic acid (ZA) or the receptor activator of NF-κB ligand (RANKL) inhibitor OPG-Fc, utilizing previously published ONJ animal models. Mice were treated with vehicle (veh), ZA, or OPG-Fc for 11 weeks to induce ONJ, and antiresorptives were discontinued for 6 or 10 weeks. Maxillae and mandibles were examined by μCT imaging and histologically. ONJ features in ZA and OPG-Fc groups included periosteal bone deposition, empty osteocyte lacunae, osteonecrotic areas, and bone exposure, each of which substantially resolved 10 weeks after discontinuing OPG-Fc but not ZA. Full recovery of tartrate-resistant acid phosphatase-positive (TRAP+) osteoclast numbers occurred after discontinuing OPG-Fc but not ZA. Our data provide the first experimental evidence demonstrating that discontinuation of a RANKL inhibitor, but not a bisphosphonate, reverses features of osteonecrosis in mice. It remains unclear whether antiresorptive discontinuation increases the risk of skeletal-related events in patients with bone metastases or fracture risk in osteoporosis patients, but these preclinical data may nonetheless help to inform discussions on the rationale for a "drug holiday" in managing the ONJ patient. PMID:25727550

  15. OPG-Fc but Not Zoledronic Acid Discontinuation Reverses Osteonecrosis of the Jaws (ONJ) in Mice

    PubMed Central

    de Molon, Rafael Scaf; Shimamoto, Hiroaki; Bezouglaia, Olga; Pirih, Flavia Q; Dry, Sarah M; Kostenuik, Paul; Boyce, Rogely W; Dwyer, Denise; Aghaloo, Tara L; Tetradis, Sotirios

    2016-01-01

    Osteonecrosis of the jaws (ONJ) is a significant complication of antiresorptive medications, such as bisphosphonates and denosumab. Antiresorptive discontinuation to promote healing of ONJ lesions remains highly controversial and understudied. Here, we investigated whether antiresorptive discontinuation alters ONJ features in mice, employing the potent bisphosphonate zoledronic acid (ZA) or the receptor activator of NF-κB ligand (RANKL) inhibitor OPG-Fc, utilizing previously published ONJ animal models. Mice were treated with vehicle (veh), ZA, or OPG-Fc for 11 weeks to induce ONJ, and antiresorptives were discontinued for 6 or 10 weeks. Maxillae and mandibles were examined by µCT imaging and histologically. ONJ features in ZA and OPG-Fc groups included periosteal bone deposition, empty osteocyte lacunae, osteonecrotic areas, and bone exposure, each of which substantially resolved 10 weeks after discontinuing OPG-Fc but not ZA. Full recovery of tartrate-resistant acid phosphatase-positive (TRAP+) osteoclast numbers occurred after discontinuing OPG-Fc but not ZA. Our data provide the first experimental evidence demonstrating that discontinuation of a RANKL inhibitor, but not a bisphosphonate, reverses features of osteonecrosis in mice. It remains unclear whether antiresorptive discontinuation increases the risk of skeletal-related events in patients with bone metastases or fracture risk in osteoporosis patients, but these preclinical data may nonetheless help to inform discussions on the rationale for a “drug holiday” in managing the ONJ patient. PMID:25727550

  16. SPG/IND-induced septic shock in a LPS-low responder strain, C3H/HeJ mice.

    PubMed

    Saito, Maki; Nameda, Sachiko; Miura, Noriko N; Adachi, Yoshiyuki; Ohno, Naohito

    2008-05-01

    The administration of beta-glucan (sonifilan; SPG) in combination with a non-steroidal anti-inflammatory drug, indomethacin (IND), induced lethal septic shock in mice. To demonstrate the influence of bacterial lipopolysaccharide (LPS) in this lethal toxicity, LPS non-responder C3H/HeJ mice were used to compare features of sepsis and physicochemical parameters in the present study. The administration of SPG and IND induced the death of C3H/HeJ mice, lowering rectal temperature, reducing body weight, increasing serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels, shortening the gastrointestinal tract, and increasing the GOT/GPT level. Microbial translocation to various organs was also significantly increased. These results strongly suggested that LPS-non-responding strain also induced septic shock in this experimental model, and other pathogen-associated molecular patterns (PAMPs) may significantly contribute to the septic shock. PMID:18093793

  17. HIF2α cooperates with RAS to promote lung tumorigenesis in mice

    PubMed Central

    Kim, William Y.; Perera, Samanthi; Zhou, Bing; Carretero, Julian; Yeh, Jen Jen; Heathcote, Samuel A.; Jackson, Autumn L.; Nikolinakos, Petros; Ospina, Beatriz; Naumov, George; Brandstetter, Kathleyn A.; Weigman, Victor J.; Zaghlul, Sara; Hayes, D. Neil; Padera, Robert F.; Heymach, John V.; Kung, Andrew L.; Sharpless, Norman E.; Kaelin, William G.; Wong, Kwok-Kin

    2009-01-01

    Members of the hypoxia-inducible factor (HIF) family of transcription factors regulate the cellular response to hypoxia. In non–small cell lung cancer (NSCLC), high HIF2α levels correlate with decreased overall survival, and inhibition of either the protein encoded by the canonical HIF target gene VEGF or VEGFR2 improves clinical outcomes. However, whether HIF2α is causal in imparting this poor prognosis is unknown. Here, we generated mice that conditionally express both a nondegradable variant of HIF2α and a mutant form of Kras (KrasG12D) that induces lung tumors. Mice expressing both Hif2a and KrasG12D in the lungs developed larger tumors and had an increased tumor burden and decreased survival compared with mice expressing only KrasG12D. Additionally, tumors expressing both KrasG12D and Hif2a were more invasive, demonstrated features of epithelial-mesenchymal transition (EMT), and exhibited increased angiogenesis associated with mobilization of circulating endothelial progenitor cells. These results implicate HIF2α causally in the pathogenesis of lung cancer in mice, demonstrate in vivo that HIF2α can promote expression of markers of EMT, and define HIF2α as a promoter of tumor growth and progression in a solid tumor other than renal cell carcinoma. They further suggest a possible causal relationship between HIF2α and prognosis in patients with NSCLC. PMID:19662677

  18. Loss of Bace1 in Mice Does Not Alter the Severity of Caerulein Induced Pancreatitis

    PubMed Central

    Heindl, Mario; Tuennemann, Jan; Sommerer, Ines; Mössner, Joachim; Hoffmeister, Albrecht

    2015-01-01

    Context Beta-site alpha-amyloid protein cleaving enzyme1 (BACE1) plays a key role in the pathogenesis of Alzheimer’s disease. Additional to its moderate expression in the brain, high levels of BACE1 mRNA were found in the pancreas. Murine Bace1 has been immunohistochemicaly detected at the apical pole of acinar cells within the exocrine pancreas of mice and Bace1 activity was observed in pancreatic juice. In vitro experiments revealed enteropeptidase as a putative substrate for Bace1 suggesting a role in acute pancreatitis. Objective The aim of this study was to address a protective mechanism of Bace1 in acute experimental pancreatitis in mice. Methods Acute experimental pancreatitis was induced by intraperitoneal injection of caerulein in homozygote Bace1-/- mice and wild type mice. Serum and tissue analyses were carried out after 4 h, 8 h and 24 h. Measurement of plasma amylase and lipase was performed to confirm pancreatitis induction. In order to assess the severity of pancreatitis H&E stained pancreatic sections were examined regarding edema, inflammation and apoptosis. Immunohistochemical detection of myeloperoxidase (MPO) positive cells was carried out to further quantify the extent of inflammation. Expression of Bace2 within the pancreas was analyzed by immunohistochemistry and RT-qPCR. Results We demonstrate that total loss of Bace1 in mice leads to no alterations in the course of acute experimental caerulein-pancreatitis. Bace1-/- mice develop a moderate pancreatitis that is comparable in histomorphological and serological features with those seen in wild type mice. Discussion We discuss the results in the context of the applied caerulein induced edematous pancreatitis model and possible compensatory mechanisms via Bace2 that might be responsible for the observed results. PMID:25961820

  19. LIMB Demonstration Project Extension

    SciTech Connect

    Not Available

    1989-06-15

    The basic goal of the Limestone Injection Multistage 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.

  20. 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.

  1. 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.

  2. Mars Umbilical Technology Demonstrator

    NASA Technical Reports Server (NTRS)

    Houshangi, Nasser

    2000-01-01

    The objective of this project is to develop a autonomous umbilical mating for the mars umbilical technology demonstrator. The Mars Umbilical Technology Demonstrator (MUTD) shall provide electrical power and fiber optic data cable connections between two simulated mars vehicles. The Omnibot is used to provide the mobile base for the system. The mate to umbilical plate is mounted on a three axis Cartesian table, which is installed on the Omnibot mobile base. The Omnibot is controlled in a teleoperated mode. The operator using the vision system will guide the Omnibot to get close to the mate to plate. The information received from four ultrasonic sensors is used to identify the position of mate to plate and mate the umbilical plates autonomously. A successful experimentation verifies the approach.

  3. 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.

  4. LIMB Demonstration Project Extension

    SciTech Connect

    Not Available

    1989-03-15

    The basic goal of the Limestone Injection Multistage 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.

  5. LIMB Demonstration Project Extension

    SciTech Connect

    Not Available

    1988-12-15

    The basic goal of the Limestone Injection Multistage 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.

  6. 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)

  7. 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.

  8. 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…

  9. 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)

  10. 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.

  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. ECM-Dependence of Endothelial Progenitor Cell Features.

    PubMed

    Siavashi, Vahid; Nassiri, Seyed Mahdi; Rahbarghazi, Reza; Vafaei, Rana; Sariri, Reyhaneh

    2016-08-01

    Preserving self-renewal, multipotent capacity, and large-scale expansion of highly functional progenitor cells, including endothelial progenitor cells (EPCs), is a controversial issue. These current limitations, therefore, raise the need of developing promising in vitro conditions for prolonged expansion of EPCs without loss of their stemness feature. In the current study, the possible role of three different natural extracellular substrates, including collagen, gelatin, and fibronectin, on multiple parameters of EPCs such as cell morphology, phenotype, clonogenic, and vasculogenic properties was scrutinized. Next, EPCs from GFP-positive mice were pre-expanded on each of these ECM substrates and then systemically transplanted into sublethaly irradiated mice to analyze the potency of these cells for marrow reconstitution. Our results revealed considerable promise for fibronectin for EPC expansion with maintenance of stemness characteristics, whereas gelatin and collagen matrices directed the cells toward a mature endothelial phenotype. Transplantation of EPCs pre-expanded on fibronectin resulted in widespread distribution and appropriate engraftment to various tissues with habitation in close association with the microvasculature. In addition, fibronectin pre-expanded cells were gradually enriched in the bone marrow after transplantation, resulting in marrow repopulation and hematologic recovery, leading to improved survival of recipient mice whereas gelatin- and collagen-expanded cells failed to reconstitute the bone marrow. This study demonstrated that, cell characteristics of in vitro expanded EPCs are determined by the subjacent matrix. Fibronectin-expanded EPCs are heralded as a source of great promise for bone marrow reconstitution and neo-angiogenesis in therapeutic bone marrow transplantation. J. Cell. Biochem. 117: 1934-1946, 2016. © 2016 Wiley Periodicals, Inc. PMID:26756870

  13. 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)

  14. Hardware demonstration of flexible beam control

    NASA Technical Reports Server (NTRS)

    Schaechter, D. B.

    1980-01-01

    An experiment employing a pinned-free flexible beam has been constructed to demonstrate and verify several facets of the control of flexible structures. The desired features of the experiment are to demonstrate active shape control, active dynamic control, adaptive control, various control law design approaches, and associated hardware requirements and mechanization difficulties. This paper contains the analytical work performed in support of the facility development, the final design specifications, control law synthesis, and some preliminary results.

  15. 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.

  16. 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.

  17. Santa Clara Demonstration Status

    SciTech Connect

    Leo, Anthony J.; Skok, Andrew J.; O'Shea, Thomas P.

    1996-08-01

    Fuel Cell Engineering Corporation (FCE) is in the fourth year of a DOE Cooperative Agreement Program (private-sector cost-shared) aimed at the demonstration of ERC's direct carbonate fuel cell (DFC) technology at full scale. FCE is a wholly owned subsidiary of Energy Research Corporation (ERC), which has been pursuing the development of the DFC for commercialization near the end of this decade. The DFC produces power directly from hydrocarbon fuels electrochemically, without the need for external reforming or intermediate mechanical conversion steps. As a result, the DFC has the potential to achieve very high efficiency with very low levels of environmental emissions. Modular DFC power plants, which can be shop-fabricated and sited near the user, are ideally suited for distributed generation, cogeneration, industrial, and defense applications. This project is an integral part of the ERC effort to commercialize the technology to serve these applications. Potential users of the commercial DFC power plant under development at ERC will require that the technology be demonstrated at or near the full scale of the commercial products. The objective of the Santa Clara Demonstration Project (SCDP) is to provide the first such demonstration of the technology. The approach ERC has taken in the commercialization of the DFC is described in detail elsewhere [1]. Briefly, an aggressive core technology development program is in place which is focused by ongoing contact with customers and vendors to optimize the design of the commercial power plant. ERC has selected a 2.85 MW power plant unit for initial market entry. Two ERC subsidiaries are supporting the commercialization effort: The Fuel Cell Manufacturing Corporation (FCMC) and the Fuel Cell Engineering Corporation (FCE). FCMC manufactures carbonate stacks and multi-stack modules, currently from its manufacturing facility in Torrington, CT. FCE is responsible for power plant design, integration of all subsystems, sales

  18. 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

  19. 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.

  20. 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.

  1. Residential Transactive Control Demonstration

    SciTech Connect

    Widergren, Steven E.; Fuller, Jason C.; Marinovici, Maria C.; Somani, Abhishek

    2014-02-19

    Arguably the most exciting aspect of the smart grid vision is the full participation of end-use resources with all forms of generation and energy storage in the reliable and efficient operation of an electric power system. Engaging all of these resources in a collaborative manner that respects the objectives of each resource, is sensitive to the system and local constraints of electricity flow, and scales to the large number of devices and systems participating is a grand challenge. Distributed decision-making system approaches have been presented and experimentation is underway. This paper reports on the preliminary findings of a residential demand response demonstration that uses the bidding transactions of supply and end-use air conditioning resources communicating with a real-time, 5 minute market to balance the various needs of the participants on a distribution feeder. The nature of the demonstration, the value streams being explored, and the operational scenarios implemented to characterize the system response are summarized along with preliminary findings.

  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. Whirl/whip demonstration

    NASA Technical Reports Server (NTRS)

    Grissom, R.

    1985-01-01

    Fluid flow in bearings and seals, set in motion by shaft rotation, generates dynamic forces which may result in a well recognized instability known as whirl and whip. These are lateral, forward precessional, self excited, subsynchronous vibrations in which the amplitude may vary from very small to nearly the limit of the bearing or seal clearances. Oil whirl in lubricated bearings, in particular, typically occurs at somewhat less than half rotative speed. As the rotative speed increases, the frequency relationship remains constant until the whirl frequency approaches the first balance resonance. Now the whirl is smoothly replaced by whip at a nearly constant frequency asymptotically approaching first balance resonance, independent of increasing rotative speed. Changes in bearing/seal radial loading can permit, prevent, or eliminate this instability. The oil whirl/whip rig demonstrates the effects of fluid dynamic forces generated by the rotating shaft. At low rotative speeds, this produces changes of the journal static equilibrium position within the bearing. The demonstrator shows the relationship between any load direction and the average journal equilibrium position. At higher rotative speeds, the instability threshold is observed as a function of unidirectional radial load, unbalance, and rotor configuration.

  4. SSME Key Operations Demonstration

    NASA Technical Reports Server (NTRS)

    Anderson, Brian; Bradley, Michael; Ives, Janet

    1997-01-01

    A Space Shuttle Main Engine (SSME) test program was conducted between August 1995 and May 1996 using the Technology Test Bed (TTB) Engine. SSTO vehicle studies have indicated that increases in the propulsion system operating range can save significant weight and cost at the vehicle level. This test program demonstrated the ability of the SSME to accommodate a wide variation in safe operating ranges and therefore its applicability to the SSTO mission. A total of eight tests were completed with four at Marshall Space Flight Center's Advanced Engine Test Facility and four at the Stennis Space Center (SSC) A-2 attitude test stand. Key demonstration objectives were: 1) Mainstage operation at 5.4 to 6.9 mixture ratio; 2) Nominal engine start with significantly reduced engine inlet pressures of 50 psia LOX and 38 psia fuel; and 3) Low power level operation at 17%, 22%, 27%, 40%, 45%, and 50% of Rated Power Level. Use of the highly instrumented TTB engine for this test series has afforded the opportunity to study in great detail engine system operation not possible with a standard SSME and has significantly contributed to a greater understanding of the capabilities of the SSME and liquid rocket engines in general.

  5. 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.

  6. 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

  7. 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

  8. 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…

  9. 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.

  10. Adding Feminist Therapy to Videotape Demonstrations.

    ERIC Educational Resources Information Center

    Konrad, Jennifer L.; Yoder, Janice D.

    2000-01-01

    Provides directions for presenting a 32-minute series of four videotape segments that highlights the fundamental features of four approaches to psychotherapy, extending its reach to include a feminist perspective. Describes the approaches and included segments. Reports that students' comments demonstrate that the video sequence provided a helpful…

  11. 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.

  12. Fusion power demonstration

    SciTech Connect

    Henning, C.D.; Logan, B.G.

    1983-09-01

    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.

  13. 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.

  14. Structural assembly demonstration experiment

    NASA Technical Reports Server (NTRS)

    Stokes, J. W.

    1982-01-01

    The experiment is of an operational variety, designed to assess crew capability in Large Space System (LSS) assembly. The six Structural Assembly Demonstration Experiment objectives include: (1) the establishment of a quantitative correlation between LSS neutral buoyancy simulation and on-orbit assembly operations in order to enhance the validity of those assembly simulations; (2) the quantitative study of the capabilities and mechanics of human assembly in an Extravehicular Activity environment; (3) the further corroboration of the LSS Assembly Analysis cost algorithm through the obtainment of hard data base information; (4) the verification of LSS assembly techniques and timeless, as well as the identification of crew imposed loads and assembly aid requirements and concepts; (5) verification of a Launch/Assembly Platform structure concept for other LSS missions; and (6) lastly, to advance thermal control concepts through a flexible heat pipe.

  15. Fusion Power Demonstration III

    SciTech Connect

    Lee, J.D.

    1985-07-01

    This is the third in the series of reports covering the Fusion Power Demonstration (FPD) design study. This volume considers the FPD-III configuration that incorporates an octopole end plug. As compared with the quadrupole end-plugged designs of FPD-I and FPD-II, this octopole configuration reduces the number of end cell magnets and shortens the minimum ignition length of the central cell. The end-cell plasma length is also reduced, which in turn reduces the size and cost of the end cell magnets and shielding. As a contiuation in the series of documents covering the FPD, this report does not stand alone as a design description of FPD-III. Design details of FPD-III subsystems that do not differ significantly from those of the FPD-II configuration are not duplicated in this report.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. Collaborative Writing Features

    ERIC Educational Resources Information Center

    Yong Mei Fung

    2010-01-01

    As part of a research study on collaborative writing, this paper discusses defining and facilitating features that occur during face-to-face collaboration, based on the literature and research. The defining features are mutual interaction, negotiations, conflict, and shared expertise. Facilitating features include affective factors, use of L1,…

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Feature-by-Feature – Evaluating De Novo Sequence Assembly

    PubMed Central

    Vezzi, Francesco; Narzisi, Giuseppe; Mishra, Bud

    2012-01-01

    The whole-genome sequence assembly (WGSA) problem is among one of the most studied problems in computational biology. Despite the availability of a plethora of tools (i.e., assemblers), all claiming to have solved the WGSA problem, little has been done to systematically compare their accuracy and power. Traditional methods rely on standard metrics and read simulation: while on the one hand, metrics like N50 and number of contigs focus only on size without proportionately emphasizing the information about the correctness of the assembly, comparisons performed on simulated dataset, on the other hand, can be highly biased by the non-realistic assumptions in the underlying read generator. Recently the Feature Response Curve (FRC) method was proposed to assess the overall assembly quality and correctness: FRC transparently captures the trade-offs between contigs' quality against their sizes. Nevertheless, the relationship among the different features and their relative importance remains unknown. In particular, FRC cannot account for the correlation among the different features. We analyzed the correlation among different features in order to better describe their relationships and their importance in gauging assembly quality and correctness. In particular, using multivariate techniques like principal and independent component analysis we were able to estimate the “excess-dimensionality” of the feature space. Moreover, principal component analysis allowed us to show how poorly the acclaimed N50 metric describes the assembly quality. Applying independent component analysis we identified a subset of features that better describe the assemblers performances. We demonstrated that by focusing on a reduced set of highly informative features we can use the FRC curve to better describe and compare the performances of different assemblers. Moreover, as a by-product of our analysis, we discovered how often evaluation based on simulated data, obtained with state of the art

  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. Corynebacterium parvum augments antibody production in splenectomized mice and mice with sham operations.

    PubMed Central

    Hebert, J C; Ershler, W B; Gamelli, R L

    1985-01-01

    The antibody response to a variety of antigens, including pneumococcal polysaccharides, is diminished in splenectomized (splx) mice. We investigated the capacity for the biological response modifier Corynebacterium parvum to augment antibody production in splx and sham-splx mice inoculated with pneumococcal polysaccharides and tetanus toxoid. As expected, antibody response to tetanus toxoid was similar in both splx mice and sham-splx mice. C. parvum augmented anti-tetanus toxoid antibody in both sham-splx (P less than 0.05) and splx mice (P less than 0.05). Antibody against pneumococcal type 3 polysaccharides was decreased in splx mice compared with sham-splx mice (P less than 0.05). Both groups treated coincidently with C. parvum and pneumococcal type 3 polysaccharides demonstrated a biphasic antibody response which was greater than that observed in saline-treated controls (sham-splx, P less than 0.001; splx, P less than 0.05). Whereas the secondary peak response to pneumococcal type 3 polysaccharides after treatments with C. parvum appears to be due to persistent elevations of immunoglobulin G and immunoglobulin M in sham-splx mice, it is primarily due to antibody of the immunoglobulin G class alone in the splx mice. PMID:3997248

  8. 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.

  9. Deficient Wnt signalling triggers striatal synaptic degeneration and impaired motor behaviour in adult mice

    PubMed Central

    Galli, Soledad; Lopes, Douglas M.; Ammari, Rachida; Kopra, Jaakko; Millar, Sarah E.; Gibb, Alasdair; Salinas, Patricia C.

    2014-01-01

    Synapse degeneration is an early and invariant feature of neurodegenerative diseases. Indeed, synapse loss occurs prior to neuronal degeneration and correlates with the symptom severity of these diseases. However, the molecular mechanisms that trigger synaptic loss remain poorly understood. Here we demonstrate that deficient Wnt signalling elicits synaptic degeneration in the adult striatum. Inducible expression of the secreted Wnt antagonist Dickkopf1 (Dkk1) in adult mice (iDkk1) decreases the number of cortico-striatal glutamatergic synapses and of D1 and D2 dopamine receptor clusters. Synapse loss occurs in the absence of axon retraction or cell death. The remaining excitatory terminals contain fewer synaptic vesicles and have a reduced probability of evoked transmitter release. IDkk1 mice show impaired motor coordination and are irresponsive to amphetamine. These studies identify Wnts as key endogenous regulators of synaptic maintenance and suggest that dysfunction in Wnt signalling contributes to synaptic degeneration at early stages in neurodegenerative diseases. PMID:25318560

  10. 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.

  11. 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. PMID:18704188

  12. 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.

  13. 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)

  14. Mthfr as a modifier of the retinal phenotype of Crb1(rd8/rd8) mice.

    PubMed

    Markand, Shanu; Saul, Alan; Tawfik, Amany; Cui, Xuezhi; Rozen, Rima; Smith, Sylvia B

    2016-04-01

    Mutations in crumb homologue 1 (CRB1) in humans are associated with Leber's congenital amaurosis (LCA) and retinitis pigmentosa (RP). There is no clear genotype-phenotype correlation for human CRB1 mutations in RP and LCA. The high variability in clinical features observed in CRB1 mutations suggests that environmental factors or genetic modifiers influence severity of CRB1 related retinopathies. Retinal degeneration 8 (rd8) is a spontaneous mutation in the Crb1 gene (Crb1(rdr/rd8)). Crb1(rdr/rd8) mice present with focal disruption in the outer retina manifesting as white spots on fundus examination. Mild retinal dysfunction with decreased b-wave amplitude has been reported in Crb1(rdr/rd8) mice at 18 months. Methylene tetrahydrofolate reductase (MTHFR) is a crucial enzyme of homocysteine metabolism. MTHFR mutations are prevalent in humans and are linked to a broad spectrum of disorders including cardiovascular and neurodegenerative diseases. We recently reported the retinal phenotype in Mthfr-deficient (Mthfr(+/-)) heterozygous mice. At 24 weeks the mice showed decreased RGC function, thinner nerve fiber layer, focal areas of vascular leakage and 20% fewer cells in the ganglion cell layer (GCL). Considering the variability in CRB1-related retinopathies and the high occurrence of human MTHFR mutations we evaluated whether Mthfr deficiency influences rd8 retinal phenotype. Mthfr heterozygous mice with rd8 mutations (Mthfr(+/-)(rd8/rd8)) and Crb(rd8/rd8) mice (Mthfr(+/+rd8/rd8)) mice were subjected to comprehensive retinal evaluation using ERG, fundoscopy, fluorescein angiography (FA), morphometric and retinal flat mount immunostaining analyses of isolectin-B4 at 8-54 wks. Assessment of retinal function revealed a significant decrease in the a-, b- and c-wave amplitudes in Mthfr(+/-)(rd8/rd8) mice at 52 wks. Fundoscopic evaluation demonstrated the presence of signature rd8 spots in Mthfr(+/+rd8/rd8) mice and an increase in the extent of these rd8 spots in Mthfr

  15. Altered lipid metabolism in Hfe-knockout mice promotes severe NAFLD and early fibrosis.

    PubMed

    Tan, Terrence C H; Crawford, Darrell H G; Jaskowski, Lesley A; Murphy, Therese M; Heritage, Mandy L; Subramaniam, V Nathan; Clouston, Andrew D; Anderson, Gregory J; Fletcher, Linda M

    2011-11-01

    The HFE protein plays a crucial role in the control of cellular iron homeostasis. Steatosis is commonly observed in HFE-related iron-overload disorders, and current evidence suggests a causal link between iron and steatosis. Here, we investigated the potential contribution of HFE mutations to hepatic lipid metabolism and its role in the pathogenesis of nonalcoholic fatty liver disease. Wild-type (WT) and Hfe knockout mice (Hfe(-/-)) were fed either standard chow, a monounsaturated low fat, or a high-fat, high-carbohydrate diet (HFD) and assessed for liver injury, body iron status, and markers of lipid metabolism. Despite hepatic iron concentrations and body weights similar to WT controls, Hfe(-/-) mice fed the HFD developed severe hypoxia-related steatohepatitis, Tnf-α activation, and mitochondrial respiratory complex and antioxidant dysfunction with early fibrogenesis. These features were associated with an upregulation in the expression of genes involved in intracellular lipid synthesis and trafficking, while transcripts for mitochondrial fatty acid β-oxidation and adiponectin signaling-related genes were significantly attenuated. In contrast, HFD-fed WT mice developed bland steatosis only, with no inflammation or fibrosis and no upregulation of lipogenesis-related genes. A HFD led to reduced hepatic iron in Hfe(-/-) mice compared with chow-fed mice, despite higher serum iron, decreased hepcidin expression, and increased duodenal ferroportin mRNA. In conclusion, our results demonstrate that Hfe(-/-) mice show defective hepatic-intestinal iron and lipid signaling, which predispose them toward diet-induced hepatic lipotoxicity, accompanied by an accelerated progression of injury to fibrosis. PMID:21817060

  16. 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

  17. Increased Spontaneous Otoacoustic Emissions in Mice with a Detached Tectorial Membrane.

    PubMed

    Cheatham, Mary Ann; Ahmad, Aisha; Zhou, Yingjie; Goodyear, Richard J; Dallos, Peter; Richardson, Guy P

    2016-04-01

    Mutations in genes encoding tectorial membrane (TM) proteins are a significant cause of human hereditary hearing loss (Hildebrand et al. 2011), and several mouse models have been developed to study the functional significance of this accessory structure in the mammalian cochlea. In this study, we use otoacoustic emissions (OAE), signals obtained from the ear canal that provide a measure of cochlear function, to characterize a mouse in which the TM is detached from the spiral limbus due to an absence of otoancorin (Otoa, Lukashkin et al. 2012). Our results demonstrate that spontaneous emissions (SOAE), sounds produced in the cochlea without stimulation, increase dramatically in mice with detached TMs even though their hearing sensitivity is reduced. This behavior is unusual because wild-type (WT) controls are rarely spontaneous emitters. SOAEs in mice lacking Otoa predominate around 7 kHz, which is much lower than in either WT animals when they generate SOAEs or in mutant mice in which the TM protein Ceacam16 is absent (Cheatham et al. 2014). Although both mutants lack Hensen's stripe, loss of this TM feature is only observed in regions coding frequencies greater than ~15 kHz in WT mice so its loss cannot explain the low-frequency, de novo SOAEs observed in mice lacking Otoa. The fact that ~80 % of mice lacking Otoa produce SOAEs even when they generate smaller distortion product OAEs suggests that the active process is still functioning in these mutants but the system(s) involved have become less stable due to alterations in TM structure. PMID:26691158

  18. 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.

  19. 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.

  20. 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

  1. Icariin, a phosphodiesterase-5 inhibitor, improves learning and memory in APP/PS1 transgenic mice by stimulation of NO/cGMP signalling.

    PubMed

    Jin, Feng; Gong, Qi-Hai; Xu, Ya-Sha; Wang, Li-Na; Jin, Hai; Li, Fei; Li, Li-Sheng; Ma, Yue-Ming; Shi, Jing-Shan

    2014-06-01

    Phosphodiesterase-5 (PDE5) inhibitors are predominantly used in the treatment of erectile dysfunction, and have been recently shown to have a potential therapeutic effect for the treatment of Alzheimer's disease (AD) through stimulation of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signalling by elevating cGMP, which is a secondary messenger involved in processes of neuroplasticity. In the present study, the effects of a PDE5 inhibitor, icarrin (ICA), on learning and memory as well as the pathological features in APP/PS1 transgenic AD mice were investigated. Ten-month-old APP/PS1 transgenic mice overexpressing human amyloid precursor protein (APP695swe) and presenilin 1 (PS1-dE9) were given ICA (30 and 60 mg/kg) or sildenafil (SIL) (2 mg/kg), age-matched wild-type (WT) mice were given ICA (60 mg/kg), and APP/PS1 and WT control groups were given an isovolumic vehicle orally twice a day for four months. Results demonstrated that ICA treatments significantly improved learning and memory of APP/PS1 transgenic mice in Y-maze tasks. The amyloid precursor protein (APP), amyloid-beta (Aβ1-40/42) and PDE5 mRNA and/or protein levels were increased in the hippocampus and cortex of APP/PS1 mice, and ICA treatments decreased these physiopathological changes. Furthermore, ICA-treated mice showed an increased expression of three nitric oxide synthase (NOS) isoforms at both mRNA and protein levels, together with increased NO and cGMP levels in the hippocampus and cortex of mice. These findings demonstrate that ICA improves learning and memory functions in APP/PS1 transgenic mice possibly through the stimulation of NO/cGMP signalling and co-ordinated induction of NOS isoforms. PMID:24513083

  2. Retinal Vascular Abnormalities in NEMO-Deficient Mice: An Animal Model for Incontinentia Pigmenti

    PubMed Central

    Oster, Stephen F.; McLeod, D. Scott; Otsuji, T.; Goldberg, Morton F.; Lutty, Gerard A.

    2016-01-01

    The majority of patients with incontinentia pigmenti (IP) have a mutation in the nuclear factor-kappa-β essential modulator (NEMO) gene, and mice with a targeted deletion of NEMO exhibit skin pathology remarkably similar to the human disease. This study characterizes the retinal vascular abnormalities of NEMO-deficient mice, and compares this phenotype to known features of human IP. Nineteen heterozygous NEMO-deficient female mice, ages ranging from post-natal day 8 (P-8) through 6.5 months of life, were studied. Eyes were sectioned and stained either whole or as retinal flat mounts after incubation for enzyme histochemical demonstration of ADPase, which labels the vasculature. With maturation, retinal arteriolar abnormalities became evident at 3 months of age. Global assessment of the retinal vasculature with ADPase staining showed increased arteriolar tortuosity. Microscopic examination of sections of ADPase-incubated retinas revealed arteriolar luminal narrowing due to endothelial cell hypertrophy and increased basement membrane deposition. Venous morphology was normal. This study characterized the histological retinal phenotype of heterozygous NEMO-deficient female mice. Most striking were retinal arteriolar abnormalities, including luminal narrowing, endothelial cell hypertrophy, and basement membrane thickening. Retinal flat mounts revealed arteriolar tortuosity without evidence of vaso-occlusion or neovascularization. PMID:19068214

  3. Treatment-induced prevention of learning deficits in newborn mice with brain lesions.

    PubMed

    Bouslama, M; Chauvière, L; Fontaine, R H; Matrot, B; Gressens, P; Gallego, J

    2006-08-25

    Perinatal brain injuries often result in irreversible learning disabilities, which manifest in early childhood. The molecular and cellular mechanisms of these injuries and potential pharmacological treatments are emerging, chiefly from studies in newborn rodents. In newborn mice, experimentally induced lesions can be dramatically reduced by appropriate neuroprotective treatments. However, the early effectiveness of these treatments in preserving cognition remained unknown. Here, we addressed this issue by using intracerebral ibotenate to induce excitotoxic brain lesions in 5-day-old mice (postnatal day 5). On postnatal days 6-7, we tested spontaneous preference for maternal odors, as an index of odor memory, and conditioned preference for an artificial odor previously paired with stroking, as an index of associative learning. Brain-lesioned newborn mice showed normal general status and preference for maternal odors. In contrast, odor conditioning was severely impaired. A previous study showed that fructose 1,6-biphosphate acted as a neuroprotective agent which significantly reduced neocortical lesion size. In the present study, treating the newborn mice with fructose 1,6-biphosphate 15 min before the ibotenate injection reduced neocortical lesion size and restored conditioning. This demonstrates, for the first time, that neuroprotective treatment can protect some features of early cognition. PMID:16713117

  4. Effects and mechanisms of cavidine protecting mice against LPS-induced endotoxic shock.

    PubMed

    Li, Weifeng; Zhang, Hailin; Niu, Xiaofeng; Wang, Xiumei; Wang, Yu; He, Zehong; Yao, Huan

    2016-08-15

    LPS sensitized mice are usually considered as an experimental model of endotoxin shock. The present study aims to evaluate effects of cavidine on LPS-induced endotoxin shock. Mice were intraperitoneally administrated with cavidine (1, 3 and 10mg/kg) or DEX (5mg/kg) at 1 and 12h before injecting LPS (30mg/kg) intraperitoneally. Blood samples, liver, lung and kidney tissues were harvested after LPS injection. The study demonstrated that pretreatment with cavidine reduced the mortality of mice during 72h after endotoxin injection. In addition, cavidine administration significantly attenuated histological pathophysiology features of LPS-induced injury in lung, liver and kidney. Furthermore, cavidine administration inhibited endotoxin-induced production of pro-inflammatory cytokines including TNF-α, IL-6 and HMGB1. Moreover, cavidine pretreatment attenuated the phosphorylation of mitogen-activated protein kinase primed by LPS. In summary, cavidine protects mice against LPS-induced endotoxic shock via inhibiting early pro-inflammatory cytokine TNF-α, IL-6 and late-phase cytokine HMGB1, and the modulation of HMGB1 may be related with MAPK signal pathway. PMID:27260672

  5. 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. PMID:19663508

  6. Long-term effects of high-fat or high-carbohydrate diets on glucose tolerance in mice with heterozygous carnitine palmitoyltransferase-1a deficiency

    PubMed Central

    Nyman, L R; Tian, L; Hamm, D A; Schoeb, T R; Gower, B A; Nagy, T R; Wood, P A

    2011-01-01

    Background: Abnormal fatty acid metabolism is an important feature in the mechanisms of insulin resistance and β-cell dysfunction. Carnitine palmitoyltransferase-1a (CPT-1a, liver isoform) has a pivotal role in the regulation of mitochondrial fatty acid oxidation. We investigated the role of CPT-1a in the development of impaired glucose tolerance using a mouse model for CPT-1a deficiency when challenged by either a high-carbohydrate (HCD) or a high-fat diet (HFD) for a total duration of up to 46 weeks. Methods: Insulin sensitivity and glucose tolerance were assessed in heterozygous CPT-1a-deficient (CPT-1a+/−) male mice after being fed either a HCD or a HFD for durations of 28 weeks and 46 weeks. Both glucose and insulin tolerance tests were used to investigate β-cell function and insulin sensitivity. Differences in islet insulin content and hepatic steatosis were evaluated by morphological analysis. Results: CPT-1a+/− mice were more insulin-sensitive than CPT-1a+/+ mice when fed either HCD or HFD. The increased insulin sensitivity was associated with an increased expression of Cpt-1b (muscle isoform) in liver, as well as increased microvesicular hepatic steatosis compared with CPT-1a+/+ mice. CPT-1a+/− mice were more glucose tolerant than CPT-1a+/+ mice when fed the HCD, but there was no significant difference when fed HFD. Moreover, CPT-1a+/− mice fed HFD or HCD had fewer and smaller pancreatic islets than CPT-1a+/+ mice. Conclusions: CPT-1a deficiency preserved insulin sensitivity when challenged by long-term feeding of either diet. Furthermore, CPT-1a-deficient mice had distinct phenotypes dependent on the diet fed demonstrating that both diet and genetics collectively have a role in the development of impaired glucose tolerance. PMID:22229081

  7. 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

  8. Otitis Media in Sperm-Associated Antigen 6 (Spag6)-Deficient Mice

    PubMed Central

    Li, Xiaofei; Xu, Lei; Li, Jianfeng; Li, Boqin; Bai, Xiaohui; Strauss, Jerome F.; Zhang, Zhibing; Wang, Haibo

    2014-01-01

    Mammalian SPAG6 protein is localized to the axoneme central apparatus, and it is required for normal flagella and cilia motility. Recent studies demonstrated that the protein also regulates ciliogenesis and cilia polarity in the epithelial cells of brain ventricles and trachea. Motile cilia are also present in the epithelial cells of the middle ear and Eustachian tubes, where the ciliary system participates in the movement of serous fluid and mucus in the middle ear. Cilia defects are associated with otitis media (OM), presumably due to an inability to efficiently transport fluid, mucus and particles including microorganisms. We investigated the potential role of SPAG6 in the middle ear and Eustachian tubes by studying mice with a targeted mutation in the Spag6 gene. SPAG6 is expressed in the ciliated cells of middle ear epithelial cells. The orientation of the ciliary basal feet was random in the middle ear epithelial cells of Spag6-deficient mice, and there was an associated disrupted localization of the planar cell polarity (PCP) protein, FZD6. These features are associated with disordered cilia orientation, confirmed by scanning electron microscopy, which leads to uncoordinated cilia beating. The Spag6 mutant mice were also prone to develop OM. However, there were no significant differences in bacterial populations, epithelial goblet cell density, mucin expression and Eustachian tube angle between the mutant and wild-type mice, suggesting that OM was due to accumulation of fluid and mucus secondary to the ciliary dysfunction. Our studies demonstrate a role for Spag6 in the pathogenesis of OM in mice, possibly through its role in the regulation of cilia/basal body polarity through the PCP-dependent mechanisms in the middle ear and Eustachian tubes. PMID:25393619

  9. 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.

  10. 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. PMID:26515884

  11. 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)

  12. Observational learning in C57BL/6j mice.

    PubMed

    Carlier, Pascal; Jamon, Marc

    2006-11-01

    The ability of mice to solve a complex task by observational learning was investigated with C57BL/6j mice. Four female demonstrators were trained to reliably perform a sequence that consisted in pushing a piece of food into a tube attached to the side of a puzzle box, and recovering it by opening a drawer in front of the box. They then performed this sequence in front of naive mice assigned to individual cubicles in a box with a wire mesh front arranged in a row facing the demonstrators. A total of 25 naive mice (13 males and 12 females) were used. Fifteen mice observed 14 demonstrations a day for 5 days; 10 control mice were placed in similar cubicles, but behind a plastic screen which prevented them from observing the demonstrators. The mice were post-tested in the demonstrator situation, and 6 of 15 observers immediately reproduced the complete task successfully, but none of the naive or control mice were able to solve the task. The observers and controls were then subjected to a five level individual learning schedule. Observers learned the individual task significantly faster than the controls. No sex difference was found. These results suggest that observational learning processes at work were based on stimulus enhancement and observational conditioning. PMID:16939695

  13. Adaptive unsupervised slow feature analysis for feature extraction

    NASA Astrophysics Data System (ADS)

    Gu, Xingjian; Liu, Chuancai; Wang, Sheng

    2015-03-01

    Slow feature analysis (SFA) extracts slowly varying features out of the input data and has been successfully applied on pattern recognition. However, SFA heavily relies on the constructed time series when SFA is applied on databases that neither have obvious temporal structure nor have label information. Traditional SFA constructs time series based on k-nearest neighborhood (k-NN) criterion. Specifically, the time series set constructed by k-NN criterion is likely to include noisy time series or lose suitable time series because the parameter k is difficult to determine. To overcome these problems, a method called adaptive unsupervised slow feature analysis (AUSFA) is proposed. First, AUSFA designs an adaptive criterion to generate time series for characterizing submanifold. The constructed time series have two properties: (1) two points of time series lie on the same submanifold and (2) the submanifold of the time series is smooth. Second, AUSFA seeks projections that simultaneously minimize the slowness scatter and maximize the fastness scatter to extract slow discriminant features. Extensive experimental results on three benchmark face databases demonstrate the effectiveness of our proposed method.

  14. Measuring the strength of mice.

    PubMed

    Deacon, Robert M J

    2013-01-01

    Kondziela devised the inverted screen test and published it in 1964. It is a test of muscle strength using all four limbs. Most normal mice easily score maximum on this task; it is a quick but insensitive gross screen, and the weights test described in this article will provide a finer measure of muscular strength. There are also several strain gauge-based pieces of apparatus available commercially that will provide more graded data than the inverted screen test, but their cost may put them beyond the reach of many laboratories which do not specialize in strength testing. Hence in 2000 a cheap and simple apparatus was devised by the author. It consists of a series of chain links of increasing length, attached to a "fur collector" a ball of fine wire mesh sold for preventing limescale build up in hard water areas. An accidental observation revealed that mice could grip these very tightly, so they proved ideal as a grip point for a weight-lifting apparatus. A common fault with commercial strength meters is that the bar or other grip feature is not thin enough for mice to exert a maximum grip. As a general rule, the thinner the wire or bar, the better a mouse can grip with its small claws. This is a pure test of strength, although as for any test motivational factors could potentially play a role. The use of scale collectors, however, seems to minimize motivational problems as the motivation appears to be very high for most normal young adult mice. PMID:23770643

  15. 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).

  16. Gait recognition based on fusion features

    NASA Astrophysics Data System (ADS)

    Wu, Haizhen; Jiang, Jiafu; Chen, Xi

    2009-10-01

    Gait recognition and analysis is a promising biometrics technology finding applications in numerous sectors of our society. This paper proposes a new fusion algorithm where the static and dynamic features are fused to obtain optimal performance. The new fusion algorithm divides decision situations into two categories. The wavelet moment is used to describe the static features of gait sequence images, and the three widths of the body contour are used to describe the dynamic features. In addition, the Principal Component Analysis (PCA) for feature transformation of spatial templates is proposed. The experimental results demonstrate that the proposed algorithm performs an encouraging recognition rate.

  17. 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

  18. 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

  19. Hepatic immunophenotyping for streptozotocin-induced hyperglycemia in mice.

    PubMed

    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

  20. 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

  1. RNA interference improves myopathic phenotypes in mice over-expressing FSHD region gene 1 (FRG1).

    PubMed

    Wallace, Lindsay M; Garwick-Coppens, Sara E; Tupler, Rossella; Harper, Scott Q

    2011-11-01

    Muscular dystrophies, and other diseases of muscle, arise from recessive and dominant gene mutations. Gene replacement strategies may be beneficial for the former, while gene silencing approaches may provide treatment for the latter. In the last two decades, muscle-directed gene therapies were primarily focused on treating recessive disorders. This disparity at least partly arose because feasible mechanisms to silence dominant disease genes lagged behind gene replacement strategies. With the discovery of RNA interference (RNAi) and its subsequent development as a promising new gene silencing tool, the landscape has changed. In this study, our objective was to demonstrate proof-of-principle for RNAi therapy of a dominant myopathy in vivo. We tested the potential of adeno-associated viral (AAV)-delivered therapeutic microRNAs, targeting the human Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1), to correct myopathic features in mice expressing toxic levels of human FRG1 (FRG1(-high) mice). We found that FRG1 gene silencing improved muscle mass, strength, and histopathological abnormalities associated with muscular dystrophy in FRG1(-high) mice, thereby demonstrating therapeutic promise for treatment of dominantly inherited myopathies using RNAi. This approach potentially applies to as many as 29 different gene mutations responsible for myopathies inherited as dominant disorders. PMID:21730972

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

    PubMed Central

    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

  3. RNA Interference Improves Myopathic Phenotypes in Mice Over-expressing FSHD Region Gene 1 (FRG1)

    PubMed Central

    Wallace, Lindsay M; Garwick-Coppens, Sara E; Tupler, Rossella; Harper, Scott Q

    2011-01-01

    Muscular dystrophies, and other diseases of muscle, arise from recessive and dominant gene mutations. Gene replacement strategies may be beneficial for the former, while gene silencing approaches may provide treatment for the latter. In the last two decades, muscle-directed gene therapies were primarily focused on treating recessive disorders. This disparity at least partly arose because feasible mechanisms to silence dominant disease genes lagged behind gene replacement strategies. With the discovery of RNA interference (RNAi) and its subsequent development as a promising new gene silencing tool, the landscape has changed. In this study, our objective was to demonstrate proof-of-principle for RNAi therapy of a dominant myopathy in vivo. We tested the potential of adeno-associated viral (AAV)-delivered therapeutic microRNAs, targeting the human Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1), to correct myopathic features in mice expressing toxic levels of human FRG1 (FRG1−high mice). We found that FRG1 gene silencing improved muscle mass, strength, and histopathological abnormalities associated with muscular dystrophy in FRG1−high mice, thereby demonstrating therapeutic promise for treatment of dominantly inherited myopathies using RNAi. This approach potentially applies to as many as 29 different gene mutations responsible for myopathies inherited as dominant disorders. PMID:21730972

  4. 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

  5. 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.

  6. The Point-of-View in Feature Writing.

    ERIC Educational Resources Information Center

    Scruton, Judson

    1979-01-01

    Discusses Tom Wolfe's point of view techniques and uses excerpts from two feature articles to demonstrate the basic point of view question for feature writers: how close do they want to get to their subjects? (GT)

  7. JCE Feature Columns

    NASA Astrophysics Data System (ADS)

    Holmes, Jon L.

    1999-05-01

    The Features area of JCE Online is now readily accessible through a single click from our home page. In the Features area each column is linked to its own home page. These column home pages also have links to them from the online Journal Table of Contents pages or from any article published as part of that feature column. Using these links you can easily find abstracts of additional articles that are related by topic. Of course, JCE Online+ subscribers are then just one click away from the entire article. Finding related articles is easy because each feature column "site" contains links to the online abstracts of all the articles that have appeared in the column. In addition, you can find the mission statement for the column and the email link to the column editor that I mentioned above. At the discretion of its editor, a feature column site may contain additional resources. As an example, the Chemical Information Instructor column edited by Arleen Somerville will have a periodically updated bibliography of resources for teaching and using chemical information. Due to the increase in the number of these resources available on the WWW, it only makes sense to publish this information online so that you can get to these resources with a simple click of the mouse. We expect that there will soon be additional information and resources at several other feature column sites. Following in the footsteps of the Chemical Information Instructor, up-to-date bibliographies and links to related online resources can be made available. We hope to extend the online component of our feature columns with moderated online discussion forums. If you have a suggestion for an online resource you would like to see included, let the feature editor or JCE Online (jceonline@chem.wisc.edu) know about it. JCE Internet Features JCE Internet also has several feature columns: Chemical Education Resource Shelf, Conceptual Questions and Challenge Problems, Equipment Buyers Guide, Hal's Picks, Mathcad

  8. β-Arrestin-1 deficiency protects mice from experimental colitis.

    PubMed

    Lee, Taehyung; Lee, Eunhee; Irwin, Regina; Lucas, Peter C; McCabe, Laura R; Parameswaran, Narayanan

    2013-04-01

    β-Arrestins are intracellular scaffolding proteins that modulate specific cell signaling pathways. Recent studies, in both cell culture and in vivo models, have demonstrated an important role for β-arrestin-1 in inflammation. However, the role of β-arrestin-1 in the pathogenesis of inflammatory bowel disease (IBD) is not known. Our goal was to investigate the role of β-arrestin-1 in IBD using mouse models of colitis. To this end, we subjected wild-type (WT) and β-arrestin-1 knockout (β-arr-1(-/-)) mice to colitis induced by trinitrobenzenesulfonic acid or dextran sulfate sodium and examined the clinical signs, gross pathology, and histopathology of the colon, as well as inflammatory components. The β-arr-1(-/-) mice displayed significantly attenuated colitis, compared with WT mice, in both models. Consistent with the phenotypic observations, histological examination of the colon revealed attenuated disease pathology in the β-arr-1(-/-) mice. Our results further demonstrate that β-arr-1(-/-) mice are deficient in IL-6 expression in the colon, but have higher expression of the anti-inflammatory IL-10 family of cytokines. Our results also demonstrate diminished ERK and NFκB pathways in the colons of β-arr-1(-/-) mice, compared with WT mice. Taken together, our results demonstrate that decreased IL-6 production and enhanced IL-10 and IL-22 production in β-arrestin-1-deficient mice likely lead to attenuated gut inflammation. PMID:23395087

  9. Engineering humanized mice for improved hematopoietic reconstitution

    PubMed Central

    Drake, Adam C; Chen, Qingfeng; Chen, Jianzhu

    2012-01-01

    Humanized mice are immunodeficient animals engrafted with human hematopoietic stem cells that give rise to various lineages of human blood cells throughout the life of the mouse. This article reviews recent advances in the generation of humanized mice, focusing on practical considerations. We discuss features of different immunodeficient recipient mouse strains, sources of human hematopoietic stem cells, advances in expansion and genetic modification of hematopoietic stem cells, and techniques to modulate the cytokine environment of recipient mice, in order to enhance reconstitution of specific human blood lineage cells. We highlight the opportunities created by new technologies and discuss practical considerations on how to make best use of the widening array of basic models for specific research applications. PMID:22425741

  10. 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.

  11. Trim33/Tif1γ is involved in late stages of granulomonopoiesis in mice.

    PubMed

    Chrétien, Marie-Lorraine; Legouge, Caroline; Martin, Romain Z; Hammann, Arlette; Trad, Malika; Aucagne, Romain; Largeot, Anne; Bastie, Jean-Noël; Delva, Laurent; Quéré, Ronan

    2016-08-01

    Trim33/Tif1γ (Trim33) is a member of the tripartite motif family. Using a conditional hematopoietic-specific Trim33 knock-out (Trim33(Δ/Δ)) mouse, we showed previously that Trim33 deficiency in hematopoietic stem cells leads to severe defects in hematopoiesis, resembling the main features of human chronic myelomonocytic leukemia. We also demonstrated that Trim33 is involved in hematopoietic aging through TGFβ signaling. Nevertheless, how Trim33 contributes to the terminal stages of myeloid differentiation remains to be clarified. We reveal here the crucial role of Trim33 expression in the control of mature granulomonocytic differentiation. An important component of Trim33-deficient mice is the alteration of myeloid differentiation, as characterized by dysplastic features, abnormal granulocyte and monocyte maturation, and the expansion of CD11b(+)Ly6G(high)Ly6C(low) myeloid cells, which share some features with polymorphonuclear-myeloid-derived suppressor cells. Moreover, in Trim33(Δ/Δ) mice, we observed the alteration of CSF-1-mediated macrophage differentiation in association with the lack of Csf-1 receptor. Altogether, these results indicate that Trim33 deficiency leads to the expansion of a subset of myeloid cells characterizing the myelodysplastic/myeloproliferative neoplasm. PMID:27130375

  12. 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.

  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. 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. PMID:26433049

  15. 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.

  16. Generation of Transgenic Mice

    PubMed Central

    Cho, Andrew; Haruyama, Naoto; Kulkarni, Ashok B.

    2009-01-01

    This unit describes detailed step-by-step protocols, reagents, and equipment required for successful generation of transgenic mice using pronuclear injection. The experimental methods and practical tips given here will help guide beginners in understanding what is required and what to avoid in these standard protocols for efficiently generating transgenic mice. PMID:19283729

  17. Development of spontaneous neuropathy in NF-κBp50-deficient mice by calcineurin-signal involving impaired NF-κB activation

    PubMed Central

    Nakamura-Yanagidaira, Tomoko; Takahashi, Yasuko; Sano, Kenji; Murata, Toshinori

    2011-01-01

    Purpose The transcriptional regulator, nuclear factor-kappa B (NF-κB)/Rel family are involved in neuronal cell death and survival. Previously, we reported that NF-κBp50-deficient (p50-deficient) mice exhibit many features resembling human normal tension glaucoma (NTG). The developmental mechanism of human NTG is not clearly understood, and a radical curative treatment has yet to be established. Our aim is to elucidate the signal cascade which mediates the spontaneous optic neuropathy in p50-deficient mice as a model of NTG. Methods To demonstrate the expression and activation of pro-apoptotic factors, which mediate the death of retinal ganglion cells (RGCs) in p50-deficient mice, western blot (WB) and luciferase reporter assays with retinas from p50-deficient and wild type mice, and cultured RGC-5 cells were performed. Furthermore, we tested the neuroprotective effects of chemical reagents (memantine, lomerizine, and tacrolimus) against N-methyl-D-aspartate (NMDA)-susceptible RGC damage according to in vitro experiments with RGC-5 cells. To elucidate the NF-κB-mediated death signaling, the effects of chemical reagents on spontaneous optic neuropathy were examined by histopathological studies. Results WB experiments and luciferase reporter assays showed that NF-κB-inducible BCL2-associated X protein (Bax) and a pro-apoptotic factor, activated caspase 3 were expressed in the retina of p50-deficient mice as well as NMDA-treated RGC-5 cells. Further, the constitutivelyactivecleaved forms of calcineurin (CaN), which havebeen reported to lead to apoptosis, were detected in the retina of p50-deficient mice as well as NMDA-treated RGC-5 cells. Pre-treatment with tacrolimus markedlyprotected RGC-5 cells from NMDA-induced neurotoxicity, and then both spontaneous RGC death and degenerative changes to the optic nerve in p50-deficient mice were significantlyreduced by the chronic administration of tacrolimus. The experiments with cultured RGC-5 cells supported the results

  18. Features in Saturn's rings

    NASA Technical Reports Server (NTRS)

    Esposito, Larry W.; Harris, Craig C.; Simmons, Karen E.

    1987-01-01

    A systematic, uniform search of Voyage 2 photopolarimeter system (PSS) data set for all significant features of Saturn's rings is described. On August 25, 1981, the PSS observed the occultation of the star Delta Scorpii by the rings of Saturn, and the timing of the data taking was rapid enough that the spatial resolution in the radial direction in the ring plane was better than 100 m. Tabular information and figures for 216 significant features that were found are presented.

  19. Feature Characterization Library

    Energy Science and Technology Software Center (ESTSC)

    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.

  20. 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

  1. Dehydration Parameters and Standards for Laboratory Mice

    PubMed Central

    Bekkevold, Christine M; Robertson, Kimberly L; Reinhard, Mary K; Battles, August H; Rowland, Neil E

    2013-01-01

    Water deprivation and restriction are common features of many physiologic and behavioral studies; however, there are no data-driven humane standards regarding mice on water deprivation or restriction studies to guide IACUC, investigators, and veterinarians. Here we acutely deprived outbred CD1 mice of water for as long as 48 h or restricted them to a 75% or 50% water ration; physical and physiologic indicators of dehydration were measured. With acute water deprivation, the appearance and attitude of mice deteriorated after 24 h, and weight loss exceeded 15%. Plasma osmolality was increased, and plasma volume decreased with each time interval. Plasma corticosterone concentration increased with duration of deprivation. There were no differences in any dehydration measures between mice housed in conventional static cages or ventilated racks. Chronic water restriction induced no significant changes compared with ad libitum availability. We conclude that acute water deprivation of as long as 24 h produces robust physiologic changes; however, deprivation in excess of 24 h is not recommended in light of apparent animal distress. Although clearly thirsty, mice adapt to chronic water restriction of as much as 50% of the ad libitum daily ration that is imposed over an interval of as long as 8 d. PMID:23849404

  2. Knockout of Foxp2 disrupts vocal development in mice.

    PubMed

    Castellucci, Gregg A; McGinley, Matthew J; McCormick, David A

    2016-01-01

    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. PMID:26980647

  3. 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.

  4. 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.

  5. 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.

  6. Developmental consequences of in utero sodium arsenate exposure in mice with folate transport deficiencies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies have demonstrated that mice lacking a functional folate binding protein 2 gene (Folbp2'/') were significantly more sensitive to in utero arsenic exposure than were the wild-type mice similarly exposed. When these mice were fed a folate-deficient diet, the embryotoxic effect of arsen...

  7. BIOSYNTHESIS OF DIMETHYLNITROSAMINE IN DIMETHYLAMINE-TREATED MICE AFTER EXPOSURE TO NITROGEN DIOXIDE

    EPA Science Inventory

    These studies demonstrate the nitrosating potential of NO2 in vivo in 1CR mice. Groups of mice were gavaged with 2 mg dimethylamine (DMA) and exposed to NO2 at levels from 0.04 to 44.5 ppm for periods up to 4 hours. Mice were individually frozen and blended to a powder, aliquots ...

  8. 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

  9. 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. PMID:24120400

  10. The Stimulus Properties of LSD in C57BL/6 Mice1

    PubMed Central

    Winter, J. C.; Kiers, A. K.; Zimmerman, M. D.; Reissig, C. J; Eckler, J.R.; Ullrich, T.; Rice, K. C.; Rabin, R. A.; Richards, J. B.

    2005-01-01

    Rationale Drug-induced stimulus control has proven to be a powerful tool for the assessment of a wide range of psychoactive drugs. Though a variety of species have been employed, the majority of studies have been in the rat. However, with the development of techniques which permit the genetic modification of mice, the latter species has taken on new importance. Lysergic acid diethylamide [LSD], the prototypic indoleamine hallucinogen, has not previously been trained as a discriminative stimulus in mice. Objective To demonstrate the feasibility of LSD-induced stimulus control in the mouse and to provide a preliminary characterization of the stimulus properties of LSD in that species. Methods Male C57BL/6 mice were trained using a left or right nose-poke operant on a fixed-ratio 10, water reinforced task following the injection of lysergic acid diethylamide [LSD, 0.17 or 0.30 mg/kg, SC; 15 min pretreatment] or vehicle. Results Stimulus control was established in 6 of 16 mice at a dose of LSD of 0.17 mg/kg after 39 sessions. An increase in dose to 0.30 mg/kg for the remaining mice resulted in stimulus control in an additional 5 subjects. In the low dose group, subsequent experiments demonstrated an orderly dose-effect relationship for LSD and a rapid offset of drug action with an absence of LSD effects 60 min after injection. When LSD [0.17 mg/kg] was administered in combination with the selective 5-HT2A antagonist, M100907, LSD-appropriate responding was significantly but incompletely reduced to approximately 50%; concurrently, response rates declined significantly. In mice trained with a dose of LSD of 0.30 mg/kg, full generalization to the phenethylamine hallucinogen, [-]-2,5-dimethoxy-4-methylamphetamine [DOM] was observed. Conclusions The present data demonstrate the feasibility of LSD-induced stimulus control in the mouse. The general features of stimulus control by LSD in the mouse closely resemble those observed in the rat but the present data suggest that

  11. 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)

  12. 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.

  13. 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 …

  14. Pharmacogenomic effect of vitamin E on kidney structure and function in transgenic mice with the haptoglobin 2-2 genotype and diabetes mellitus.

    PubMed

    Nakhoul, Farid M; Miller-Lotan, Rachel; Awad, Hoda; Asleh, Rabea; Jad, Kheir; Nakhoul, Nakhoul; Asaf, Roy; Abu-Saleh, Niroz; Levy, Andrew P

    2009-04-01

    Polymorphic loci regulating oxidative stress are potential susceptibility genes for diabetic nephropathy (DN). Haptoglobin (Hp) is an antioxidant protein which serves to protect against oxidative stress induced by extracorpuscular hemoglobin. There are two alleles at the Hp locus, 1 and 2. The Hp 1 protein is a superior antioxidant to the Hp 2 protein. The Hp 2 allele has been associated with increased prevalence of DN and appears to be associated with a more rapid progression to end-stage renal disease. We sought to recapitulate this association between Hp genotype and DN in mice genetically modified at the Hp locus. We assessed morphometric, histologic, and functional parameters involved in the development and progression of DN in mice with diabetes mellitus (DM) with either the Hp 2-2 or Hp 1-1 genotype. Morphometric analysis demonstrated that glomerular and proximal tubular hypertrophy were significantly increased in Hp 2-2 DM mice. Histological analysis demonstrated that Hp 2-2 DM mice had significantly more collagen type IV, smooth muscle actin, and increased renal iron deposition. Studies of renal function demonstrated creatinine clearance time and albuminuria were increased in Hp 2-2 DM mice. Vitamin E provided significant protection against the development of functional and histological features characteristic of DN to Hp 2-2 DM but not to Hp 1-1 DM mice. These studies serve to strengthen the association between the Hp 2-2 genotype and diabetic renal disease and suggest a pharmacogenomic interaction may exist between the Hp genotype and vitamin E. PMID:19176700

  15. 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.

  16. 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.

  17. 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. PMID:25393935

  18. 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.

  19. 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.

  20. 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.

  1. Local Feature Selection for Data Classification.

    PubMed

    Armanfard, Narges; Reilly, James P; Komeili, Majid

    2016-06-01

    Typical feature selection methods choose an optimal global feature subset that is applied over all regions of the sample space. In contrast, in this paper we propose a novel localized feature selection (LFS) approach whereby each region of the sample space is associated with its own distinct optimized feature set, which may vary both in membership and size across the sample space. This allows the feature set to optimally adapt to local variations in the sample space. An associated method for measuring the similarities of a query datum to each of the respective classes is also proposed. The proposed method makes no assumptions about the underlying structure of the samples; hence the method is insensitive to the distribution of the data over the sample space. The method is efficiently formulated as a linear programming optimization problem. Furthermore, we demonstrate the method is robust against the over-fitting problem. Experimental results on eleven synthetic and real-world data sets demonstrate the viability of the formulation and the effectiveness of the proposed algorithm. In addition we show several examples where localized feature selection produces better results than a global feature selection method. PMID:26390448

  2. Comparative Functional Genomics Analysis of NNK Tobacco-Carcinogen Induced Lung Adenocarcinoma Development in Gprc5a-Knockout Mice

    PubMed Central

    Men, Taoyan; van Pelt, Carolyn; Lotan, Dafna; Lotan, Reuben

    2010-01-01

    Background Improved understanding of lung cancer development and progression, including insights from studies of animal models, are needed to combat this fatal disease. Previously, we found that mice with a knockout (KO) of G-protein coupled receptor 5A (Gprc5a) develop lung tumors after a long latent period (12 to 24 months). Methodology/Principal Findings To determine whether a tobacco carcinogen will enhance tumorigenesis in this model, we administered 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) i.p. to 2-months old Gprc5a-KO mice and sacrificed groups (n = 5) of mice at 6, 9, 12, and 18 months later. Compared to control Gprc5a-KO mice, NNK-treated mice developed lung tumors at least 6 months earlier, exhibited 2- to 4-fold increased tumor incidence and multiplicity, and showed a dramatic increase in lesion size. A gene expression signature, NNK-ADC, of differentially expressed genes derived by transcriptome analysis of epithelial cell lines from normal lungs of Gprc5a-KO mice and from NNK-induced adenocarcinoma was highly similar to differential expression patterns observed between normal and tumorigenic human lung cells. The NNK-ADC expression signature also separated both mouse and human adenocarcinomas from adjacent normal lung tissues based on publicly available microarray datasets. A key feature of the signature, up-regulation of Ube2c, Mcm2, and Fen1, was validated in mouse normal lung and adenocarcinoma tissues and cells by immunohistochemistry and western blotting, respectively. Conclusions/Significance Our findings demonstrate that lung tumorigenesis in the Gprc5a-KO mouse model is augmented by NNK and that gene expression changes induced by tobacco carcinogen(s) may be conserved between mouse and human lung epithelial cells. Further experimentation to prove the reliability of the Gprc5a knockout mouse model for the study of tobacco-induced lung carcinogenesis is warranted. PMID:20686609

  3. Knockout of Epstein-Barr Virus BPLF1 Retards B-Cell Transformation and Lymphoma Formation in Humanized Mice

    PubMed Central

    Li, Guangming; Montgomery, Stephanie A.; Montgomery, Nathan D.; Su, Lishan; Pagano, Joseph S.

    2015-01-01

    ABSTRACT BPLF1 of Epstein-Barr virus (EBV) is classified as a late lytic cycle protein but is also found in the viral tegument, suggesting its potential involvement at both initial and late stages of viral infection. BPLF1 possesses both deubiquitinating and deneddylating activity located in its N-terminal domain and is involved in processes that affect viral infectivity, viral DNA replication, DNA repair, and immune evasion. A recently constructed EBV BPLF1-knockout (KO) virus was used in conjunction with a humanized mouse model that can be infected with EBV, enabling the first characterization of BPLF1 function in vivo. Results demonstrate that the BPLF1-knockout virus is approximately 90% less infectious than wild-type (WT) virus. Transformation of human B cells, a hallmark of EBV infection, was delayed and reduced with BPLF1-knockout virus. Humanized mice infected with EBV BPLF1-knockout virus showed less weight loss and survived longer than mice infected with equivalent infectious units of WT virus. Additionally, splenic tumors formed in 100% of mice infected with WT EBV but in only 25% of mice infected with BPLF1-KO virus. Morphological features of spleens containing tumors were similar to those in EBV-induced posttransplant lymphoproliferative disease (PTLD) and were almost identical to cases seen in human diffuse large B-cell lymphoma. The presence of EBV genomes was detected in all mice that developed tumors. The results implicate BPLF1 in human B-cell transformation and tumor formation in humanized mice. PMID:26489865

  4. 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.

  5. 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,…

  6. Feature- Spring 2010

    Cancer.gov

    NCI CAM News is a twice yearly newsletter produced by OCCAM to bring you information on the National Cancer Institute's latest CAM activities. Featured in the newsletter are: Highlights of NCI-sponsored CAM research Resources for researchers such as funding opportunities and grant writing workshops Upcoming meetings and lectures

  7. 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

  8. 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…

  9. Development of a computational high-throughput tool for the quantitative examination of dose-dependent histological features.

    PubMed

    Nault, Rance; Colbry, Dirk; Brandenberger, Christina; Harkema, Jack R; Zacharewski, Timothy R

    2015-04-01

    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

  10. 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

  11. 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.

  12. Enhanced tumor formation in cyclin D1 x transforming growth factor beta1 double transgenic mice with characterization by magnetic resonance imaging.

    PubMed

    Deane, Natasha G; Lee, Haakil; Hamaamen, Jalal; Ruley, Anna; Washington, M Kay; LaFleur, Bonnie; Thorgeirsson, Snorri S; Price, Ronald; Beauchamp, R Daniel

    2004-02-15

    Transgenic mice that overexpress cyclin D1 protein in the liver develop liver carcinomas with high penetrance. Transforming growth factor beta (TGF-beta) serves as either an epithelial cell growth inhibitor or a tumor promoter, depending on the cellular context. We interbred LFABP-cyclin D1 and Alb-TGF-beta1 transgenic mice to produce cyclin D1/TGF-beta1 double transgenic mice and followed the development of liver tumors over time, characterizing cellular and molecular changes, tumor incidence, tumor burden, and tumor physiology noninvasively by magnetic resonance imaging. Compared with age-matched LFABP-cyclin D1 single transgenic littermates, cyclin D1/TGF-beta1 mice exhibited a significant increase in tumor incidence. Tumor multiplicity, tumor burden, and tumor heterogeneity were higher in cyclin D1/TGF-beta1 mice compared with single transgenic littermates. Characteristics of cyclin D1/TGF-beta1 livers correlated with a marked induction of the peripheral periductal oval cell/stem cell compartment of the liver. A number of cancerous lesions from cyclin D1/TGF-beta1 mice exhibited unique features such as ductal plate malformations and hemorrhagic nodules. Some lesions were contiguous with the severely diseased background liver and, in some cases, replaced the normal architecture of the entire organ. Cyclin D1/TGF-beta1 lesions, in particular, were associated with malignant features such as areas of vascular invasion by hepatocytes and heterogeneous hyperintensity of signal on T2-weighted magnetic resonance imaging. These findings demonstrate that TGF-beta1 promotes stem cell activation and tumor progression in the context of cyclin D1 overexpression in the liver. PMID:14973059

  13. Combination of 3D skin surface texture features and 2D ABCD features for improved melanoma diagnosis.

    PubMed

    Ding, Yi; John, Nigel W; Smith, Lyndon; Sun, Jiuai; Smith, Melvyn

    2015-10-01

    Two-dimensional asymmetry, border irregularity, colour variegation and diameter (ABCD) features are important indicators currently used for computer-assisted diagnosis of malignant melanoma (MM); however, they often prove to be insufficient to make a convincing diagnosis. Previous work has demonstrated that 3D skin surface normal features in the form of tilt and slant pattern disruptions are promising new features independent from the existing 2D ABCD features. This work investigates that whether improved lesion classification can be achieved by combining the 3D features with the 2D ABCD features. Experiments using a nonlinear support vector machine classifier show that many combinations of the 2D ABCD features and the 3D features can give substantially better classification accuracy than using (1) single features and (2) many combinations of the 2D ABCD features. The best 2D and 3D feature combination includes the overall 3D skin surface disruption, the asymmetry and all the three colour channel features. It gives an overall 87.8 % successful classification, which is better than the best single feature with 78.0 % and the best 2D feature combination with 83.1 %. These demonstrate that (1) the 3D features have additive values to improve the existing lesion classification and (2) combining the 3D feature with all the 2D features does not lead to the best lesion classification. The two ABCD features not selected by the best 2D and 3D combination, namely (1) the border feature and (2) the diameter feature, were also studied in separate experiments. It found that inclusion of either feature in the 2D and 3D combination can successfully classify 3 out of 4 lesion groups. The only one group not accurately classified by either feature can be classified satisfactorily by the other. In both cases, they have shown better classification performances than those without the 3D feature in the combinations. This further demonstrates that (1) the 3D feature can be used to

  14. NAD metabolism in HPRT-deficient mice

    PubMed Central

    Jacomelli, Gabriella; Di Marcello, Federica; Notarantonio, Laura; Sestini, Silvia; Cerboni, Barbara; Bertelli, Matteo; Pompucci, Giuseppe; Jinnah, Hyder A.

    2016-01-01

    The activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT) is virtually absent in Lesch-Nyhan disease (LND), an X-linked genetic disorder characterized by uric acid accumulation and neurodevelopmental dysfunction. The biochemical basis for the neurological and behavioral abnormalities have not yet been completely explained. Prior studies of cells from affected patients have shown abnormalities of NAD metabolism. In the current studies, NAD metabolism was evaluated in HPRT gene knock-out mice. NAD content and the activities of the enzymes required for synthesis and breakdown of this coenzyme were investigated in blood, brain and liver of HPRT− and control mice. NAD concentration and enzyme activities were found to be significantly increased in liver, but not in brain or blood of the HPRT− mice. These results demonstrate that changes in NAD metabolism occur in response to HPRT deficiency depending on both species and tissue type. PMID:19319672

  15. MnTBAP Therapy Attenuates Renal Fibrosis in Mice with 5/6 Nephrectomy

    PubMed Central

    Yu, Jing; Mao, Song; Zhang, Yue; Gong, Wei; Jia, Zhanjun; Huang, Songming; Zhang, Aihua

    2016-01-01

    Renal fibrosis is a common pathological feature of all kinds of chronic kidney diseases (CKDs) with uncertain mechanisms. Accumulating evidence demonstrated an important role of oxidative stress in the pathogenesis of CKD. Here we hypothesized that MnTBAP (manganese (III) tetrakis (4-benzoic acid)porphyrin chloride), a cell-permeable mimic of superoxide dismutase (SOD), may protect against the fibrotic response in CKD by antagonizing oxidative stress. To verify this hypothesis, we performed experiments in tubular epithelial cells and mice with 5/6 nephrectomy (Nx). In mouse tubular epithelial cells, TGF-β1 induced a significant transition to fibrotic phenotype in line with a remarkable mitochondrial dysfunction, which was markedly improved by MnTBAP (1.14 μM) pretreatment. In remnant kidneys of 5/6 Nx mice, tubulointerstitial fibrosis occurred in parallel with mitochondrial abnormality in renal tubular cells. Administration of MnTBAP significantly attenuated the deposition of extracellular matrix as evidenced by the blocked expressions of fibronectin, collagen I, and collagen III. Masson staining also displayed an ameliorated accumulation of collagenous matrix in MnTBAP-treated mice. Moreover, MnTBAP also significantly improved the severity of proteinuria without altering CKD-related hypertension. Collectively, MnTBAP therapy served as a promising strategy in preventing renal fibrosis in CKDs possibly via antagonizing mitochondrial-derived oxidative stress and subsequent protection of mitochondrial function. PMID:26989454

  16. Arterial calcifications and increased expression of vitamin D receptor targets in mice lacking TIF1α

    PubMed Central

    Ignat, Mihaela; Teletin, Marius; Tisserand, Johan; Khetchoumian, Konstantin; Dennefeld, Christine; Chambon, Pierre; Losson, Régine; Mark, Manuel

    2008-01-01

    Calcification of arteries is a major risk factor for cardiovascular mortality in humans. Using genetic approaches, we demonstrate here that the transcriptional intermediary factor 1α (TIF1α), recently shown to function as a tumor suppressor in murine hepatocytes, also participates in a molecular cascade that prevents calcifications in arterioles and medium-sized arteries. We further provide genetic evidence that this function of TIF1α is not exerted in hepatocytes. The sites of ectopic calcifications in mutant mice lacking TIF1α resemble those seen in mice carrying an activating mutation of the calcium sensor receptor (Casr) gene and, in TIF1α-deficient kidneys, Casr expression is increased together with that of many other vitamin D receptor (VDR) direct target genes, namely Car2, Cyp24a1, Trpv5, Trpv6, Calb1, S100g, Pthlh, and Spp1. Thus, our data indicate that TIF1α represses the VDR pathway in kidney and suggest that an up-regulation of Casr expression in this organ could account for ectopic calcifications generated upon TIF1α deficiency. Interestingly, the calcifying arteriopathy of TIF1α-null mutant mice shares features with the human age-related Mönckeberg's disease and, overall, the TIF1α-null mutant pathological phenotype supports the hypothesis that aging is promoted by increased activity of the vitamin D signaling pathway. PMID:18287084

  17. 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. PMID:26921617

  18. Reduced baroreceptor sensitivity during hypotension in ANP-knockout mice.

    PubMed

    Ackermann, U; Deliva, R D

    2001-03-01

    We studied baroreflex gain in inactin-anesthetized mice that had been genetically modified to be depleted of atrial natriuretic peptide (ANP -/-). Wild-type mice (ANP +/+) served as controls. ANP -/- mice had a significantly higher basal arterial blood pressure (ABP) than ANP +/+ mice [112+/-7 vs. 80+/-5 mmHg (mean +/- SEM)]. Their basal heart rates were not different (491+/-13 vs. 446+/-19 bpm). A third group, composed of ANP +/+ mice only, was rendered acutely hypertensive by an intravenous infusion of arginine vasopressin acetate (0.3 pg bolus followed by 0.3 pg/h) so as to serve as a control for the elevated ABP in the ANP -/- mice. Transient changes in ABP were caused by bolus injections of oxymetazoline hydrochloride (1.5-3 ng) or sodium nitroprusside (20-100 ng). Baroreflex gain was calculated as the ratio of the peak heart rate change that followed the peak change in mean ABP resulting from injection of oxymetazoline or nitroprusside. There were no significant differences among the groups in their responses to transient hypertension. On the other hand, the ANP -/- mice showed a significantly depressed tachycardic response to transient hypotension when compared with the other two groups. We conclude that the ANP -/- mice are unable to increase efferent sympathetic nervous activity adequately above the high basal activity that is a feature of this animal model. PMID:11294595

  19. Transmission of multiple system atrophy prions to transgenic mice

    PubMed Central

    Watts, Joel C.; Giles, Kurt; Oehler, Abby; Middleton, Lefkos; Dexter, David T.; Gentleman, Steve M.; DeArmond, Stephen J.; Prusiner, Stanley B.

    2013-01-01

    Prions are proteins that adopt alternative conformations, which become self-propagating. Increasing evidence argues that prions feature in the synucleinopathies that include Parkinson’s disease, Lewy body dementia, and multiple system atrophy (MSA). Although TgM83+/+ mice homozygous for a mutant A53T α-synuclein transgene begin developing CNS dysfunction spontaneously at ∼10 mo of age, uninoculated TgM83+/− mice (hemizygous for the transgene) remain healthy. To determine whether MSA brains contain α-synuclein prions, we inoculated the TgM83+/− mice with brain homogenates from two pathologically confirmed MSA cases. Inoculated TgM83+/− mice developed progressive signs of neurologic disease with an incubation period of ∼100 d, whereas the same mice inoculated with brain homogenates from spontaneously ill TgM83+/+ mice developed neurologic dysfunction in ∼210 d. Brains of MSA-inoculated mice exhibited prominent astrocytic gliosis and microglial activation as well as widespread deposits of phosphorylated α-synuclein that were proteinase K sensitive, detergent insoluble, and formic acid extractable. Our results provide compelling evidence that α-synuclein aggregates formed in the brains of MSA patients are transmissible and, as such, are prions. The MSA prion represents a unique human pathogen that is lethal upon transmission to Tg mice and as such, is reminiscent of the prion causing kuru, which was transmitted to chimpanzees nearly 5 decades ago. PMID:24218576

  20. 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.

  1. Decreased Proteasomal Activity Causes Photoreceptor Degeneration in Mice

    PubMed Central

    Ando, Ryo; Noda, Kousuke; Tomaru, Utano; Kamoshita, Mamoru; Ozawa, Yoko; Notomi, Shoji; Hisatomi, Toshio; Noda, Mika; Kanda, Atsuhiro; Ishibashi, Tatsuro; Kasahara, Masanori; Ishida, Susumu

    2014-01-01

    Purpose. To study the retinal degeneration caused by decreased proteasomal activity in β5t transgenic (β5t-Tg) mice, an animal model of senescence acceleration. Methods. β5t-Tg mice and age-matched littermate control (WT) mice were used. Proteasomal activities and protein level of poly-ubiquitinated protein in retinal extracts were quantified. Fundus images of β5t-Tg mice were taken and their features were assessed. For histologic evaluation, the thicknesses of inner nuclear layer (INL), outer nuclear layer (ONL), and photoreceptor outer segment (OS) were measured. For functional analysis, ERG was recorded under scotopic and photopic illumination conditions. Immunofluorescence (IF) staining and TUNEL were performed to investigate the mechanism of photoreceptor degeneration. Results. Chymotrypsin-like activity was partially suppressed in retinal tissues of β5t-Tg mice. Retinal degenerative changes with arterial attenuation were present in β5t-Tg, but not in WT mice. Inner nuclear layer thickness showed no significant change between β5t-Tg and WT mice at 1, 3, 6, and 9 months of age. By contrast, thicknesses of ONL and OS in β5t-Tg mice were significantly decreased at 3, 6, and 9 months compared with those in WT mice. Electroretinograms showed decrease of scotopic a-wave amplitude in β5t-Tg mice. The number of TUNEL-positive cells in ONL were significantly increased in β5t-Tg mice and colocalized with apoptosis-inducing factor, but not with cleaved caspase-3 and -9, indicating that the photoreceptor cell death was induced via a caspase-independent pathway. Conclusions. The current data showed that impaired proteasomal function causes photoreceptor degeneration. PMID:24994871

  2. 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

  3. Mapping Pathological Phenotypes in Reelin Mutant Mice

    PubMed Central

    Michetti, Caterina; Romano, Emilia; Altabella, Luisa; Caruso, Angela; Castelluccio, Paolo; Bedse, Gaurav; Gaetani, Silvana; Canese, Rossella; Laviola, Giovanni; Scattoni, Maria Luisa

    2014-01-01

    Autism Spectrum Disorders (ASD) are neurodevelopmental disorders with multifactorial origin characterized by social communication deficits and the presence of repetitive behaviors/interests. Several studies showed an association between the reelin gene mutation and increased risk of ASD and a reduced reelin expression in some brain regions of ASD subjects, suggesting a role for reelin deficiency in ASD etiology. Reelin is a large extracellular matrix glycoprotein playing important roles during development of the central nervous system. To deeply investigate the role of reelin dysfunction as vulnerability factor in ASD, we assessed the behavioral, neurochemical, and brain morphological features of reeler male mice. We recently reported a genotype-dependent deviation in the ultrasonic vocal repertoire and a general delay in motor development of reeler pups. We now report that adult male heterozygous (Het) reeler mice did not show social behavior and communication deficits during male–female social interactions. Wildtype and Het mice showed a typical light/dark locomotor activity profile, with a peak during the central interval of the dark phase. However, when faced with a mild stressful stimulus (a saline injection) only Het mice showed an over response to stress. In addition to the behavioral studies, we conducted high performance liquid chromatography and magnetic resonance imaging and spectroscopy to investigate whether reelin mutation influences brain monoamine and metabolites levels in regions involved in ASD. Low levels of dopamine in cortex and high levels of glutamate and taurine in hippocampus were detected in Het mice, in line with clinical data collected on ASD children. Altogether, our data detected subtle but relevant neurochemical abnormalities in reeler mice supporting this mutant line, particularly male subjects, as a valid experimental model to estimate the contribution played by reelin deficiency in the global ASD neurobehavioral phenotype. PMID

  4. 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

  5. Integrating electrostatics with demonstrations and interactive teaching

    NASA Astrophysics Data System (ADS)

    Chang, Wheijen

    2011-02-01

    Teaching electrostatics is challenging due to its complexity and high degree of abstraction. To facilitate students' understanding of the meanings and relations of the key terms, this paper describes a series of demonstrations and conceptual questions based on an interactive teaching approach. The context was an introductory university physics course for engineering and science students in Taiwan. Features of the teaching intervention include the utilization of a series of demonstrations for repeated practice applying the important concepts, the incorporation of derivations of equations and verbal elaboration of concepts, and the engagement of students in thinking and discussing. Data show that the teaching intervention benefited the students' academic performance and their satisfaction with the learning achievement.

  6. Intrinsic Feature Motion Tracking

    Energy Science and Technology Software Center (ESTSC)

    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 timemore » 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.« less

  7. Unidentified Infrared Emission Features

    NASA Astrophysics Data System (ADS)

    Joblin, Christine

    2015-03-01

    When referring to unidentified infrared emission features, one has in mind the series of aromatic IR bands (AIBs) between 3.3 and 15 μm that are observed in emission in many environments where UV photons irradiate interstellar matter. These bands are now used by astronomers to classify objects and characterize local physical conditions. However, a deep analysis cannot proceed without understanding the properties of the band carriers. Large polycyclic aromatic hydrocarbon molecules are attractive candidates but interstellar species are still poorly characterized. Various studies emphasize the need for tackling the link between molecular aromatic species, aliphatic material and very small carbonaceous grains. Other unidentified emission features such as the 6.9, 21 and 30 μm bands could be involved in the evolutionary scenario.

  8. 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.

  9. North Polar Features

    NASA Technical Reports Server (NTRS)

    2004-01-01

    28 November 2004 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows banded terrain of the north polar region of Mars. The bands are exposures of layered material, possibly composed of dust and ice. The dark, rounded to elliptical mounds in this image might be the locations of ancient sand dunes that were completely buried in the north polar layered material. In more recent times, these mounds have been exhumed from within the layered material. Alternatively, the dark features are not ancient, exhumed dunes, but perhaps the remnants of a dark layer of material that once covered the entire area shown in the image. These features are located near 79.9oN, 31.4oW. The image covers an area about 3 km (1.9 mi) wide. Sunlight illuminates the scene from the lower left.

  10. 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.…

  11. 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.

  12. 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…

  13. 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,…

  14. 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.

  15. 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)

  16. 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…

  17. 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…

  18. 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)

  19. 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…

  20. Measuring Impact of Demonstration Projects.

    ERIC Educational Resources Information Center

    Fleischman, Howard L.

    A proposed evaluation model for measuring the impact of demonstration projects in vocational education defines sets of criteria, standards, and documentation for both interim and final acceptable evidence of project impact. Interim acceptable evidence is that evidence of project success which should be expected during the demonstration grant…

  1. 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.

  2. Intestinal Microbiota of Mice Influences Resistance to Staphylococcus aureus Pneumonia.

    PubMed

    Gauguet, Stefanie; D'Ortona, Samantha; Ahnger-Pier, Kathryn; Duan, Biyan; Surana, Neeraj K; Lu, Roger; Cywes-Bentley, Colette; Gadjeva, Mihaela; Shan, Qiang; Priebe, Gregory P; Pier, Gerald B

    2015-10-01

    Th17 immunity in the gastrointestinal tract is regulated by the intestinal microbiota composition, particularly the presence of segmented filamentous bacteria (sfb), but the role of the intestinal microbiota in pulmonary host defense is not well explored. We tested whether altering the gut microbiota by acquiring sfb influences the susceptibility to staphylococcal pneumonia via induction of type 17 immunity. Groups of C57BL/6 mice which differed in their intestinal colonization with sfb were challenged with methicillin-resistant Staphylococcus aureus in an acute lung infection model. Bacterial burdens, bronchoalveolar lavage fluid (BALF) cell counts, cell types, and cytokine levels were compared between mice from different vendors, mice from both vendors after cohousing, mice given sfb orally prior to infection, and mice with and without exogenous interleukin-22 (IL-22) or anti-IL-22 antibodies. Mice lacking sfb developed more severe S. aureus pneumonia than mice colonized with sfb, as indicated by higher bacterial burdens in the lungs, lung inflammation, and mortality. This difference was reduced when sfb-negative mice acquired sfb in their gut microbiota through cohousing with sfb-positive mice or when given sfb orally. Levels of type 17 immune effectors in the lung were higher after infection in sfb-positive mice and increased in sfb-negative mice after acquisition of sfb, as demonstrated by higher levels of IL-22 and larger numbers of IL-22(+) TCRβ(+) cells and neutrophils in BALF. Exogenous IL-22 protected mice from S. aureus pneumonia. The murine gut microbiota, particularly the presence of sfb, promotes pulmonary type 17 immunity and resistance to S. aureus pneumonia, and IL-22 protects against severe pulmonary staphylococcal infection. PMID:26216419

  3. 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)

  4. 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.

  5. 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)

  6. Isidis Planitia Features

    NASA Technical Reports Server (NTRS)

    2004-01-01

    26 June 2004 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows some of the most typical features of Isidis Planitia at full (1.5 meters -- 5 feet -- per pixel) resolution. The typical features are: (1) light-toned, ripple-like dunes and (2) mounds with summit pits. The dunes are formed by wind. The double-cone feature in the lower right quarter of the image is similar to many mounds and chains of mounds or cones found all across Isidis Planitia. These were seen at lower resolution in Viking orbiter images in the 1970s and were generally considered to be either small volcanoes or ice-cored mounds known as pingoes. With high resolution MOC images, it became apparent that many of these mounds may simply be the remnants of crater and pit chain floors, elevated above the surrounding plains as the layers of rock into which they formed were stripped away. Like much of Mars, there are more questions than answers. This image is located near 8.6oN, 268.2oW, and covers an area about 1.1 km (0.7 mi) wide. Sunlight illuminates the scene from the left/lower left.

  7. Ceraunius Tholus Feature

    NASA Technical Reports Server (NTRS)

    2004-01-01

    11 December 2004 Today's Mars Picture of the Day features two images. The top picture is a mosaic of Viking orbiter images acquired in the late 1970s. The lower image is a high resolution picture from the Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC). The Viking mosaic shows Ceraunius Tholus, a volcano in the Tharsis region that was first viewed in images obtained by Mariner 9 in 1972. Several channels run down the slope of the Ceraunius Tholus volcano. The deepest of those channels ends in an elliptical crater. The elliptical crater was formed by a very oblique meteor impact. Where the channel meets the floor of the elliptical crater, there is a small mound of material. Presumably, this material was deposited in the elliptical crater after running down through the channel on the volcano's northwest flank.

    Near the top/center of the mound in the elliptical crater is a small, circular depression. Some have speculated for years that this depression is related to volcanism, others thought that it may be an impact crater. The MGS MOC image (lower of the two images) shows that crater. It is not the source of lava flows or any other volcanic features. Most likely, it is an old impact crater. This feature is located near 25.2oN, 97.7oW. The MOC image covers an area approximately 3 km (1.9 mi) wide and is illuminated by sunlight from the lower left.

  8. Effect of low frequency low energy pulsing electromagnetic fields on mice injected with cyclophosphamide

    SciTech Connect

    Cadossi, R.; Zucchini, P.; Emilia, G.; Franceschi, C.; Cossarizza, A.; Santantonio, M.; Mandolini, G.; Torelli, G. )

    1991-03-01

    C3H mice have been used to investigate the effect of a combination of cyclophosphamide (CY) and electromagnetic fields (PEMF). Mice were injected i.p. with a single dose of 200 mg/kg body weight of CY and then exposed to PEMF 24 h per day. In an initial series of experiments immediately after CY injection mice were exposed to PEMF until sacrifice. WBC counts in the peripheral blood demonstrated a quicker decline in WBC at days 1 and 2 in mice exposed to PEMF. Groups of mice were sacrificed at days 1, 4, 6, 8, and 10 after CY injection. In mice exposed to PEMF the spleen weight was less than in controls at days 6, 8, and 10. Autoradiographic studies demonstrated that the labeling index of bone marrow smears did not significantly differ between controls and experimental mice exposed to PEMF, whereas the spleen labeling index proved to be higher among control mice versus mice exposed to PEMF at day 6, and higher among mice exposed to PEMF versus controls at day 8. In a second series of experiments mice were exposed to PEMF only over the 24 h following CY injection. We found that the spleens of mice exposed to PEMF weighed less than those of controls at days 6 and 8. The labeling index of bone marrow did evidence a slight decrease among mice exposed to PEMF at days 8 and 10 after CY injection versus control mice. The spleen labeling index proved to be lower in experimental mice exposed to PEMF than in controls at days 4, 6, and 8. Mice were then injected with CY, half were exposed to PEMF, and 24 h later bone marrow was recovered from both groups of animals. The same number of bone marrow cells was injected via the tail vein into recipient mice irradiated to 8.5 Gy.

  9. Transgenic knockout mice with exclusively human sickle hemoglobinand sickle cell disease

    SciTech Connect

    Paszty, C.; Brion, C.; Manci, E.; Witkowska, E.; Stevens, M.; Narla, M.; Rubin, E.

    1997-06-13

    To create mice expressing exclusively human sicklehemoglobin (HbS), transgenic mice expressing human alpha-, gamma-, andbeta[S]-globin were generated and bred with knockout mice that haddeletions of the murine alpha- and beta-globin genes. These sickle cellmice have the major features (irreversibly sickled red cells, anemia,multiorgan pathology) found in humans with sickle cell disease and, assuch, represent a useful in vivo system to accelerate the development ofimproved therapies for this common genetic disease.

  10. Developmental onset of bilirubin-induced neurotoxicity involves Toll-like receptor 2-dependent signaling in humanized UDP-glucuronosyltransferase1 mice.

    PubMed

    Yueh, Mei-Fei; Chen, Shujuan; Nguyen, Nghia; Tukey, Robert H

    2014-02-21

    Biological and signaling events that connect developmentally induced hyperbilirubinemia to bilirubin-induced neurological dysfunction (BIND) and CNS toxicity in humans are poorly understood. In mammals, UDP-glucuronosyltransferase 1A1 (UGT1A1) is the sole enzyme responsible for bilirubin glucuronidation, a rate-limiting step necessary for bilirubin metabolism and clearance. Humanized mice that express the entire UGT1 locus (hUGT1) and the UGT1A1 gene, develop neonatal hyperbilirubinemia, with 8-10% of hUGT1 mice succumbing to CNS damage, a phenotype that is presented by uncontrollable seizures. We demonstrate that neuroinflammation and reactive gliosis are prominent features of bilirubin brain toxicity, and a disturbed redox status resulting from activation of NADPH oxidase is an important contributing mechanism found in BIND. Using knock-out mice and primary brain cells, we connect a key pattern recognition receptor, Toll-like receptor 2 (TLR2), to hyperbilirubinemia-induced signaling. We illustrate a requirement for TLR2 signaling in regulating gliosis, proinflammatory mediators, and oxidative stress when neonatal mice encounter severe hyperbilirubinemia. TLR2-mediated gliosis strongly correlates with pronounced neuroinflammation in the CNS with up-regulation of TNFα, IL-1β, and IL-6, creating a pro-inflammatory CNS environment. Gene expression and immunohistochemistry staining show that hUGT1/Tlr2(-/-) mice fail to activate glial cells, proinflammatory cytokines, and stress response genes. In addition, bilirubin-induced apoptosis was significantly enhanced by blocking TLR2 signaling indicating its anti-apoptotic property. Consequently, a higher neonatal death rate (57.1%) in hUGT1/Tlr2(-/-) mice was observed when compared with hUGT1 mice (8.7%). These results suggest that TLR2 signaling and microglia neuroinflammation are linked to a repair and/or protection mode against BIND. PMID:24403077

  11. 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.

  12. 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.

  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. 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

  15. 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.

  16. 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.

  17. Status of the Majorana Demonstrator

    DOE PAGESBeta

    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.

  18. 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.)

  19. 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)

  20. 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)