Silver and Nitrate Oppositely Modulate Antimony Susceptibility through Aquaglyceroporin 1 in Leishmania (Viannia) Species.

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Andrade, Juvana M; Baba, Elio H; Machado-de-Avila, Ricardo A; Chavez-Olortegui, Carlos; Demicheli, Cynthia P; Frézard, Frédéric; Monte-Neto, Rubens L; Murta, Silvane M F

2016-08-01

Antimony (Sb) resistance in leishmaniasis chemotherapy has become one of the major challenges to the control of this spreading worldwide public health problem. Since the plasma membrane pore-forming protein aquaglyceroporin 1 (AQP1) is the major route of Sb uptake in Leishmania, functional studies are relevant to characterize drug transport pathways in the parasite. We generated AQP1-overexpressing Leishmania guyanensis and L. braziliensis mutants and investigated their susceptibility to the trivalent form of Sb (Sb(III)) in the presence of silver and nitrate salts. Both AQP1-overexpressing lines presented 3- to 4-fold increased AQP1 expression levels compared with those of their untransfected counterparts, leading to an increased Sb(III) susceptibility of about 2-fold. Competition assays using silver nitrate, silver sulfadiazine, or silver acetate prior to Sb(III) exposure increased parasite growth, especially in AQP1-overexpressing mutants. Surprisingly, Sb(III)-sodium nitrate or Sb(III)-potassium nitrate combinations showed significantly enhanced antileishmanial activities compared to those of Sb(III) alone, especially against AQP1-overexpressing mutants, suggesting a putative nitrate-dependent modulation of AQP1 activity. The intracellular level of antimony quantified by graphite furnace atomic absorption spectrometry showed that the concomitant exposure to Sb(III) and nitrate favors antimony accumulation in the parasite, increasing the toxicity of the drug and culminating with parasite death. This is the first report showing evidence of AQP1-mediated Sb(III) susceptibility modulation by silver in Leishmania and suggests the potential antileishmanial activity of the combination of nitrate salts and Sb(III). Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Expression of aquaporin-7 and aquaporin-9 in tanycyte cells and choroid plexus during mouse estrus cycle.

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Yaba, A; Sozen, B; Suzen, B; Demir, N

2017-03-01

Tanycytes are special ependymal cells located in the ventrolateral wall and floor of the third ventricle having processes extending nuclei that regulate reproductive functions and around of vessels in median eminance. The aquaporins (AQPs) are a family of transmembrane proteins that transport water and glycerol. AQP-7 and -9 are permeable to other small molecules as glycerol and therefore called aquaglyceroporins. In this study, we aimed to show localization of AQP-7 and -9 in epithelial cells of choroid plexus and tanycytes during female mouse estrus cycle. AQP-7 and -9 proteins were detected in α2 and β1 tanycytes in prœstrus stage. Interestingly, there is no staining in estrus stage in any type of tanycytes. We observed weak immunoreactivity in α1, α2 and β1 tanycyte cells in metestrus stage for AQP-7 and α1 for AQP-9 protein. AQP-7 and -9 showed intense immunoreactivity in α2, β1 and β2 tanycyte cells during diestrus stage. Consequently, AQP-7 and -9 showed differential staining pattern in different stages of mouse estrus cycle. In the light of our findings and other recent publications, we suggest that AQP-7 and -9-mediated glycerol transport in tanycyte cells might be under hormonal control to use glycerol as a potential energy substrate during mouse estrus cycle. Copyright © 2016. Published by Elsevier Masson SAS.

Flow cytometry-assisted rapid isolation of recombinant Plasmodium berghei parasites exemplified by functional analysis of aquaglyceroporin

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Kenthirapalan, Sanketha; Waters, Andrew P.; Matuschewski, Kai; Kooij, Taco W.A.

2012-01-01

The most critical bottleneck in the generation of recombinant Plasmodium berghei parasites is the mandatory in vivo cloning step following successful genetic manipulation. This study describes a new technique for rapid selection of recombinant P. berghei parasites. The method is based on flow cytometry to isolate isogenic parasite lines and represents a major advance for the field, in that it will speed the generation of recombinant parasites as well as cut down on animal use significantly. High expression of GFP during blood infection, a prerequisite for robust separation of transgenic lines by flow cytometry, was achieved. Isogenic recombinant parasite populations were isolated even in the presence of a 100-fold excess of wild-type (WT) parasites. Aquaglyceroporin (AQP) loss-of-function mutants and parasites expressing a tagged AQP were generated to validate this approach. aqp− parasites grow normally within the WT phenotypic range during blood infection of NMRI mice. Similarly, colonization of the insect vector and establishment of an infection after mosquito transmission were unaffected, indicating that AQP is dispensable for life cycle progression in vivo under physiological conditions, refuting its use as a suitable drug target. Tagged AQP localized to perinuclear structures and not the parasite plasma membrane. We suggest that flow-cytometric isolation of isogenic parasites overcomes the major roadblock towards a genome-scale repository of mutant and transgenic malaria parasite lines. PMID:23137753

Antenatal Corticosteroids and Postnatal Fluid Restriction Produce Differential Effects on AQP3 Expression, Water Handling, and Barrier Function in Perinatal Rat Epidermis

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Johan Agren

2010-01-01

Full Text Available Loss of water through the immature skin can lead to hypothermia and dehydration in preterm infants. The water and glycerol channel aquaglyceroporin-3 (AQP3 is abundant in fetal epidermis and might influence epidermal water handling and transepidermal water flux around birth. To investigate the role of AQP3 in immature skin, we measured in vivo transepidermal water transport and AQP3 expression in rat pups exposed to clinically relevant fluid homeostasis perturbations. Preterm (E18 rat pups were studied after antenatal corticosteroid exposure (ANS, and neonatal (P1 rat pups after an 18 h fast. Transepidermal water loss (TEWL and skin hydration were determined, AQP3 mRNA was quantified by RT-PCR, and in-situ hybridization and immunocytochemistry were applied to map AQP3 expression. ANS resulted in an improved skin barrier (lower TEWL and skin hydration, while AQP3 mRNA and protein increased. Fasting led to loss of barrier integrity along with an increase in skin hydration. These alterations were not paralleled by any changes in AQP3. To conclude, antenatal corticosteroids and early postnatal fluid restriction produce differential effects on skin barrier function and epidermal AQP3 expression in the rat. In perinatal rats, AQP3 does not directly determine net water transport through the skin.

Species-Specific Antimonial Sensitivity in Leishmania Is Driven by Post-Transcriptional Regulation of AQP1

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Mandal, Goutam; Mandal, Srotoswati; Sharma, Mansi; Charret, Karen Santos; Papadopoulou, Barbara; Bhattacharjee, Hiranmoy; Mukhopadhyay, Rita

2015-01-01

Leishmania is a digenetic protozoan parasite causing leishmaniasis in humans. The different clinical forms of leishmaniasis are caused by more than twenty species of Leishmania that are transmitted by nearly thirty species of phlebotomine sand flies. Pentavalent antimonials (such as Pentostam or Glucantime) are the first line drugs for treating leishmaniasis. Recent studies suggest that pentavalent antimony (Sb(V)) acts as a pro-drug, which is converted to the more active trivalent form (Sb(III)). However, sensitivity to trivalent antimony varies among different Leishmania species. In general, Leishmania species causing cutaneous leishmaniasis (CL) are more sensitive to Sb(III) than the species responsible for visceral leishmaniasis (VL). Leishmania aquaglyceroporin (AQP1) facilitates the adventitious passage of antimonite down a concentration gradient. In this study, we show that Leishmania species causing CL accumulate more antimonite, and therefore exhibit higher sensitivity to antimonials, than the species responsible for VL. This species-specific differential sensitivity to antimonite is directly proportional to the expression levels of AQP1 mRNA. We show that the stability of AQP1 mRNA in different Leishmania species is regulated by their respective 3’-untranslated regions. The differential regulation of AQP1 mRNA explains the distinct antimonial sensitivity of each species. PMID:25714343

Expression of Aquaporins in Human Embryos and Potential Role of AQP3 and AQP7 in Preimplantation Mouse Embryo Development

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Yun Xiong

2013-05-01

Full Text Available Background/Aims: Water channels, also named aquaporins (AQPs, play crucial roles in cellular water homeostasis. Methods: RT-PCR indicated the mRNA expression of AQPs 1-5, 7, 9, and 11-12, but not AQPs 0, 6, 8, and 10 in the 2∼8-cell stage human embryos. AQP3 and AQP7 were further analyzed for their mRNA expression and protein expression in the oocyte, zygote, 2-cell embryo, 4-cell embryo, 8-cell embryo, morula, and blastocyst from both human and mouse using RT-PCR and immunofluorescence, respectively. Results: AQP3 and AQP7 were detected in all these stages. Knockdown of either AQP3 or AQP7 by targeted siRNA injection into 2-cell mouse embryos significantly inhibited preimplantation embryo development. However, knockdown of AQP3 in JAr spheroid did not affect its attachment to Ishikawa cells. Conclusion: These data demonstrate that multiple aquaporins are expressed in the early stage human embryos and that AQP3 and AQP7 may play a role in preimplantation mouse embryo development.

The Effect of a High-Protein Diet and Exercise on Cardiac AQP7 and GLUT4 Gene Expression.

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Palabiyik, Orkide; Karaca, Aziz; Taştekin, Ebru; Yamasan, Bilge Eren; Tokuç, Burcu; Sipahi, Tammam; Vardar, Selma Arzu

2016-10-01

High-protein (HP) diets are commonly consumed by athletes despite their potential health hazard, which is postulated to enforce a negative effect on bone and renal health. However, its effects on heart have not been known yet. Aquaporin-7 (AQP7) is an aquaglyceroporin that facilitates glycerol and water transport. Glycerol is an important cardiac energy production substrate, especially during exercise, in conjunction with fatty acids and glucose. Glucose transporter 4 (GLUT4) is an insulin-sensitive glucose transporter in heart. We aimed to investigate the effect of HPD on AQP7 and GLUT4 levels in the rat heart subjected to exercise. Male Sprague-Dawley rats were divided into control (n = 12), exercise (E) training (n = 10), HPD (n = 12), and HPD-E training (n = 9) groups. The HPD groups were fed a 45 % protein-containing diet 5 weeks. The HPD-E and E groups were performed the treadmill exercise during the 5-week study period. Real-time polymerase chain reaction and immunohistochemistry techniques were used to determine the gene expression and localization of AQP7 and GLUT4 in heart tissue. Results of relative gene expression were calculated by the 'Pfaffl' mathematical method using the REST program. Differences in AQP7 and GLUT4 gene expression were expressed as fold change compared to the control group. Heart weight/tibia ratio and ventricular wall thickness were evaluated as markers of cardiac hypertrophy. Further, serum glucose, glycerol, and insulin levels were also measured. AQP7 gene expression was found to be increased in the E (3.47-fold, p protein expression was also increased in the HPD and HPD-E groups (p protein expression was significantly increased in the E, HPD, and HPD-E groups compared to the control group (p = 0.024, p protein diet groups (C and E). Serum insulin levels were higher for HPD groups compared with the normal-protein diet groups (p < 0.001), whereas no differences were observed between the exercise and sedentary

Aquaglyceroporins: ancient channels for metalloids

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Bhattacharjee, Hiranmoy; Mukhopadhyay, Rita; Thiyagarajan, Saravanamuthu; Rosen, Barry P

2008-01-01

The identification of aquaglyceroporins as uptake channels for arsenic and antimony shows how these toxic elements can enter the food chain, and suggests that food plants could be genetically modified to exclude arsenic while still accumulating boron and silicon. PMID:19014407

The water channel AQP1 is expressed in human atherosclerotic vascular lesions and AQP1 deficiency augments angiotensin II-induced atherosclerosis in mice

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Wintmo, P.; Johansen, S. H.; Hansen, P. B. L.

2017-01-01

Aim: The water channel aquaporin 1 (AQP1) promotes endothelial cell migration. It was hypothesized that AQP1 promotes neovascularization and growth of atherosclerotic plaques. Methods: AQP1 immunoreactivity and protein abundance was examined in human and murine atherosclerotic lesions and aortic...... minipumps for 4 weeks. Results: In human atherosclerotic lesions and AAA, AQP1 immunoreactive protein was associated with intralesional small vessels. In ApoE-/- mouse aorta, APQ1 mRNA levels were increased with time on WD (n = 7-9, P ... increased with time on WD but was not different between ApoE-/- and AQP1-/-ApoE-/- mice at either 8 or 16 weeks (n = 13-15). Baseline blood pressure and ANGII-induced hypertension were not different between genotypes. Conclusion: AQP1 is expressed in atherosclerotic lesion neovasculature in human and mouse...

Aquaporin-11: A channel protein lacking apparent transport function expressed in brain

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Tsunenari Takashi

2006-05-01

Full Text Available Abstract Background The aquaporins are a family of integral membrane proteins composed of two subfamilies: the orthodox aquaporins, which transport only water, and the aquaglyceroporins, which transport glycerol, urea, or other small solutes. Two recently described aquaporins, numbers 11 and 12, appear to be more distantly related to the other mammalian aquaporins and aquaglyceroporins. Results We report on the characterization of Aquaporin-11 (AQP11. AQP11 RNA and protein is found in multiple rat tissues, including kidney, liver, testes and brain. AQP11 has a unique distribution in brain, appearing in Purkinje cell dendrites, hippocampal neurons of CA1 and CA2, and cerebral cortical neurons. Immunofluorescent staining of Purkinje cells indicates that AQP11 is intracellular. Unlike other aquaporins, Xenopus oocytes expressing AQP11 in the plasma membrane failed to transport water, glycerol, urea, or ions. Conclusion AQP11 is functionally distinct from other proteins of the aquaporin superfamily and could represent a new aquaporin subfamily. Further studies are necessary to elucidate the role of AQP11 in the brain.

Aqp5 is a new transcriptional target of Dot1a and a regulator of Aqp2.

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Hongyu Wu

Full Text Available Dot1l encodes histone H3 K79 methyltransferase Dot1a. Mice with Dot1l deficiency in renal Aqp2-expressing cells (Dot1l(AC develop polyuria by unknown mechanisms. Here, we report that Aqp5 links Dot1l deletion to polyuria through Aqp2. cDNA array analysis revealed and real-time RT-qPCR validated Aqp5 as the most upregulated gene in Dot1l(AC vs. control mice. Aqp5 protein is barely detectable in controls, but robustly expressed in the Dot1l(AC kidneys, where it colocalizes with Aqp2. The upregulation of Aqp5 is coupled with reduced association of Dot1a and H3 dimethyl K79 with specific subregions in Aqp5 5' flanking region in Dot1l(AC vs. control mice. In vitro studies in IMCD3, MLE-15 and 293Tcells using multiple approaches including real-time RT-qPCR, luciferase reporter assay, cell surface biotinylation assay, colocalization, and co-immunoprecipitation uncovered that Dot1a represses Aqp5. Human AQP5 interacts with AQP2 and impairs its cell surface localization. The AQP5/AQP2 complex partially resides in the ER/Golgi. Consistently, AQP5 is expressed in none of 15 normal controls, but in all of 17 kidney biopsies from patients with diabetic nephropathy. In the patients with diabetic nephropathy, AQP5 colocalizes with AQP2 in the perinuclear region and AQP5 expression is associated with impaired cellular H3 dimethyl K79. Taken together, these data for the first time identify Aqp5 as a Dot1a potential transcriptional target, and an Aqp2 binding partner and regulator, and suggest that the upregulated Aqp5 may contribute to polyuria, possibly by impairing Aqp2 membrane localization, in Dot1l(AC mice and in patients with diabetic nephropathy.

Immunohistochemical Localization of the Water Channels AQP4 and AQP5 in the Rat Pituitary Gland

International Nuclear Information System (INIS)

Matsuzaki, Toshiyuki; Inahata, Yuki; Sawai, Nobuhiko; Yang, Chun-Ying; Kobayashi, Makito; Takata, Kuniaki; Ozawa, Hitoshi

2011-01-01

The pituitary gland is composed of the adenohypophysis and neurohypophysis. The adenohypophysis contains endocrine cells, folliculo-stellate (FS) cells, and marginal layer cells, whereas the neurohypophysis mainly comprises axons and pituicytes. To understand the molecular nature of water transfer in the pituitary gland, we examined the immunohistochemical localization of the membrane water channels aquaporin-4 (AQP4) and AQP5 in rat tissue. Double immunofluorescence analysis of AQP4 and S100 protein, a known marker for FS cells, marginal layer cells, and pituicytes, clearly revealed that FS cells and marginal layer cells in the adenohypophysis and the pituicytes in pars nervosa are positive for AQP4. AQP5 was found to be localized at the apical membrane in some marginal layer cells surrounding the Rathke’s residual pouch, in which AQP4 was observed to be localized on the basolateral membranes. These results suggest the following possibilities: 1) FS cells especially require water for their functions and 2) transepithelial water transfer could occur between the lumen of Rathke’s residual pouch and the interstitial fluid in the adenohypophysis through the AQP4 and AQP5 channels in the marginal layer cells

Increased expression of AQP 1 and AQP 5 in rat lungs ventilated with low tidal volume is time dependent.

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Gustavo Fabregat

Full Text Available BACKGROUND AND GOALS: Mechanical ventilation (MV can induce or worsen pulmonary oedema. Aquaporins (AQPs facilitate the selective and rapid bi-directional movement of water. Their role in the development and resolution of pulmonary oedema is controversial. Our objectives are to determine if prolonged MV causes lung oedema and changes in the expression of AQP 1 and AQP 5 in rats. METHODS: 25 male Wistar rats were subjected to MV with a tidal volume of 10 ml/kg, during 2 hours (n = 12 and 4 hours (n = 13. Degree of oedema was compared with a group of non-ventilated rats (n = 5. The expression of AQP 1 and AQP 5 were determined by western immunoblotting, measuring the amount of mRNA (previously amplified by RT-PCR and immunohistochemical staining of AQPs 1 and 5 in lung samples from all groups. RESULTS: Lung oedema and alveolar-capillary membrane permeability did not change during MV. AQP-5 steady state levels in the western blot were increased (p<0.01 at 2 h and 4 h of MV. But in AQP-1 expression these differences were not found. However, the amount of mRNA for AQP-1 was increased at 2 h and 4 h of MV; and for AQP 5 at 4 h of MV. These findings were corroborated by representative immunohistochemical lung samples. CONCLUSION: In lungs from rats ventilated with a low tidal volume the expression of AQP 5 increases gradually with MV duration, but does not cause pulmonary oedema or changes in lung permeability. AQPs may have a protective effect against the oedema induced by MV.

Bioinformatics analysis and construction of phylogenetic tree of aquaporins from Echinococcus granulosus.

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Wang, Fen; Ye, Bin

2016-09-01

Cyst echinococcosis caused by the matacestodal larvae of Echinococcus granulosus (Eg), is a chronic, worldwide, and severe zoonotic parasitosis. The treatment of cyst echinococcosis is still difficult since surgery cannot fit the needs of all patients, and drugs can lead to serious adverse events as well as resistance. The screen of target proteins interacted with new anti-hydatidosis drugs is urgently needed to meet the prevailing challenges. Here, we analyzed the sequences and structure properties, and constructed a phylogenetic tree by bioinformatics methods. The MIP family signature and Protein kinase C phosphorylation sites were predicted in all nine EgAQPs. α-helix and random coil were the main secondary structures of EgAQPs. The numbers of transmembrane regions were three to six, which indicated that EgAQPs contained multiple hydrophobic regions. A neighbor-joining tree indicated that EgAQPs were divided into two branches, seven EgAQPs formed a clade with AQP1 from human, a "strict" aquaporins, other two EgAQPs formed a clade with AQP9 from human, an aquaglyceroporins. Unfortunately, homology modeling of EgAQPs was aborted. These results provide a foundation for understanding and researches of the biological function of E. granulosus.

Human AQP5 plays a role in the progression of chronic myelogenous leukemia (CML.

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Young Kwang Chae

2008-07-01

Full Text Available Aquaporins (AQPs have previously been associated with increased expression in solid tumors. However, its expression in hematologic malignancies including CML has not been described yet. Here, we report the expression of AQP5 in CML cells by RT-PCR and immunohistochemistry. While normal bone marrow biopsy samples (n = 5 showed no expression of AQP5, 32% of CML patient samples (n = 41 demonstrated AQP5 expression. In addition, AQP5 expression level increased with the emergence of imatinib mesylate resistance in paired samples (p = 0.047. We have found that the overexpression of AQP5 in K562 cells resulted in increased cell proliferation. In addition, small interfering RNA (siRNA targeting AQP5 reduced the cell proliferation rate in both K562 and LAMA84 CML cells. Moreover, by immunoblotting and flow cytometry, we show that phosphorylation of BCR-ABL1 is increased in AQP5-overexpressing CML cells and decreased in AQP5 siRNA-treated CML cells. Interestingly, caspase9 activity increased in AQP5 siRNA-treated cells. Finally, FISH showed no evidence of AQP5 gene amplification in CML from bone marrow. In summary, we report for the first time that AQP5 is overexpressed in CML cells and plays a role in promoting cell proliferation and inhibiting apoptosis. Furthermore, our findings may provide the basis for a novel CML therapy targeting AQP5.

Aquaporin-11 (AQP11 Expression in the Mouse Brain

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Shin Koike

2016-06-01

Full Text Available Aquaporin-11 (AQP11 is an intracellular aquaporin expressed in various tissues, including brain tissues in mammals. While AQP11-deficient mice have developed fatal polycystic kidneys at one month old, the role of AQP11 in the brain was not well appreciated. In this study, we examined the AQP11 expression in the mouse brain and the brain phenotype of AQP11-deficient mice. AQP11 messenger ribonucleic acid (mRNA and protein were expressed in the brain, but much less than in the thymus and kidney. Immunostaining showed that AQP11 was localized at the epithelium of the choroid plexus and at the endothelium of the brain capillary, suggesting that AQP11 may be involved in water transport at the choroid plexus and blood-brain barrier (BBB in the brain. The expression of AQP4, another brain AQP expressed at the BBB, was decreased by half in AQP11-deficient mice, thereby suggesting the presence of the interaction between AQP11 and AQP4. The brain of AQP11-deficient mice, however, did not show any morphological abnormalities and the function of the BBB was intact. Our findings provide a novel insight into a water transport mechanism mediated by AQPs in the brain, which may lead to a new therapy for brain edema.

Refractive-index-based screening of membrane-protein-mediated transfer across biological membranes.

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Brändén, Magnus; Tabaei, Seyed R; Fischer, Gerhard; Neutze, Richard; Höök, Fredrik

2010-07-07

Numerous membrane-transport proteins are major drug targets, and therefore a key ingredient in pharmaceutical development is the availability of reliable, efficient tools for membrane transport characterization and inhibition. Here, we present the use of evanescent-wave sensing for screening of membrane-protein-mediated transport across lipid bilayer membranes. This method is based on a direct recording of the temporal variations in the refractive index that occur upon a transfer-dependent change in the solute concentration inside liposomes associated to a surface plasmon resonance (SPR) active sensor surface. The applicability of the method is demonstrated by a functional study of the aquaglyceroporin PfAQP from the malaria parasite Plasmodium falciparum. Assays of the temperature dependence of facilitated diffusion of sugar alcohols on a single set of PfAQP-reconstituted liposomes reveal that the activation energies for facilitated diffusion of xylitol and sorbitol are the same as that previously measured for glycerol transport in the aquaglyceroporin of Escherichia coli (5 kcal/mole). These findings indicate that the aquaglyceroporin selectivity filter does not discriminate sugar alcohols based on their length, and that the extra energy cost of dehydration of larger sugar alcohols, upon entering the pore, is compensated for by additional hydrogen-bond interactions within the aquaglyceroporin pore. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Targeting aquaporin function: potent inhibition of aquaglyceroporin-3 by a gold-based compound.

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Ana Paula Martins

Full Text Available Aquaporins (AQPs are membrane channels that conduct water and small solutes such as glycerol and are involved in many physiological functions. Aquaporin-based modulator drugs are predicted to be of broad potential utility in the treatment of several diseases. Until today few AQP inhibitors have been described as suitable candidates for clinical development. Here we report on the potent inhibition of AQP3 channels by gold(III complexes screened on human red blood cells (hRBC and AQP3-transfected PC12 cells by a stopped-flow method. Among the various metal compounds tested, Auphen is the most active on AQP3 (IC(50 = 0.8±0.08 µM in hRBC. Interestingly, the compound poorly affects the water permeability of AQP1. The mechanism of gold inhibition is related to the ability of Au(III to interact with sulphydryls groups of proteins such as the thiolates of cysteine residues. Additional DFT and modeling studies on possible gold compound/AQP adducts provide a tentative description of the system at a molecular level. The mapping of the periplasmic surface of an homology model of human AQP3 evidenced the thiol group of Cys40 as a likely candidate for binding to gold(III complexes. Moreover, the investigation of non-covalent binding of Au complexes by docking approaches revealed their preferential binding to AQP3 with respect to AQP1. The high selectivity and low concentration dependent inhibitory effect of Auphen (in the nanomolar range together with its high water solubility makes the compound a suitable drug lead for future in vivo studies. These results may present novel metal-based scaffolds for AQP drug development.

In vivo studies of aquaporins 3 and 10 in human stratum corneum

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Jungersted, Jakob Mutanu; Bomholt, Julie; Bajraktari, Niada

2013-01-01

migration and proliferation with consequences for the antimicrobial defense of the skin. AQP3 and AQP10 are aqua-glyceroporins, known to transport glycerol as well as water. AQP3 is the predominant AQP in human skin and has previously been demonstrated in the basal layer of epidermis in normal human skin......, but not in stratum corneum (SC). AQP10 has not previously been identified in human skin. Previous studies have demonstrated the presence of AQP3 and AQP10 mRNA in keratinocytes. In this study, our aim was to investigate if these aquaporin proteins were actually present in human SC cells. This can be seen as a first...... step toward elucidating the possible functional role of AQP3 and AQP10 in SC hydration. Specifically we investigate the presence of AQP3 and AQP10 in vivo in human SC using “minimal-invasive” technique for obtaining SC samples. SC samples were obtained from six healthy volunteers. Western blotting...

Tubular localization and expressional dynamics of aquaporins in the kidney of seawater-challenged Atlantic salmon

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Engelund, Morten Buch; Madsen, Steffen S

2015-01-01

Most vertebrate nephrons possess an inherited ability to secrete fluid in normal or pathophysiological states. We hypothesized that renal aquaporin expression and localization are functionally regulated in response to seawater and during smoltification in Atlantic salmon and thus reflect a shift...... in renal function from filtration towards secretion. We localized aquaporins (Aqp) in Atlantic salmon renal tubular segments by immunohistochemistry and monitored their expressional dynamics using RT-PCR and immunoblotting. Three aquaporins: Aqpa1aa, Aqp1ab and Aqp8b and two aquaglyceroporins Aqp3a and Aqp......10b were localized in the kidney of salmon. The staining for all aquaporins was most abundant in the proximal kidney tubules and there was no clear effect of salinity or developmental stage on localization pattern. Aqp1aa and Aqp3a were abundant apically but extended throughout the epithelial cells...

Autoimmune AQP4 channelopathies and neuromyelitis optica spectrum disorders.

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Hinson, Shannon R; Lennon, Vanda A; Pittock, Sean J

2016-01-01

Neuromyelitis optica (NMO) spectrum disorders (SD) represent an evolving group of central nervous system (CNS)-inflammatory autoimmune demyelinating diseases unified by a pathogenic autoantibody specific for the aquaporin-4 (AQP4) water channel. It was historically misdiagnosed as multiple sclerosis (MS), which lacks a distinguishing biomarker. The discovery of AQP4-IgG moved the focus of CNS demyelinating disease research from emphasis on the oligodendrocyte and myelin to the astrocyte. NMO is recognized today as a relapsing disease, extending beyond the optic nerves and spinal cord to include brain (especially in children) and skeletal muscle. Brain magnetic resonance imaging abnormalities, identifiable in 60% of patients at the second attack, are consistent with MS in 10% of cases. NMOSD-typical lesions (another 10%) occur in AQP4-enriched regions: circumventricular organs (causing intractable nausea and vomiting) and the diencephalon (causing sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Advances in understanding the immunobiology of AQP4 autoimmunity have necessitated continuing revision of NMOSD clinical diagnostic criteria. Assays that selectively detect pathogenic AQP4-IgG targeting extracellular epitopes of AQP4 are promising prognostically. When referring to AQP4 autoimmunity, we suggest substituting the term "autoimmune aquaporin-4 channelopathy" for the term "NMO spectrum disorders." Randomized clinical trials are currently assessing the efficacy and safety of newer immunotherapies. Increasing therapeutic options based on understanding the molecular pathogenesis is anticipated to improve the outcome for patients with AQP4 channelopathy. © 2016 Elsevier B.V. All rights reserved.

Aquaporins in Spinal Cord Injury: The Janus Face of AQP4

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Nesic, Olivera; Guest, James D.; Zivadinovic, Dragoslava; Narayana, Ponnada A.; Herrera, Juan J.; Grill, Raymond J.; Mokkapati, Venkata U.L.; Gelman, Benjamin B.; Lee, Julieann

2010-01-01

Although malfunction of spinal cord water channels (aquaporins, AQP) likely contributes to severe disturbances in ion/water homeostasis after spinal cord injury (SCI), their roles are still poorly understood. Here we report and discuss the potential significance of changes in the AQP4 expression in human SCI that generates GFAP-labeled astrocytes devoid of AQP4, and GFAP-labeled astroglia that overexpress AQP4. We used a rat model of contusion SCI to study observed changes in human SCI. AQP4-negative astrocytes are likely generated during the process of SCI-induced replacement of lost astrocytes, but their origin and role in SCI remains to be investigated. We found that AQP4-overexpression is likely triggered by hypoxia. Our transcriptional profiling of injured rat cords suggests that elevated AQP4-mediated water influx accompanies increased uptake of chloride and potassium ions which represents a protective astrocytic reaction to hypoxia. However, unbalanced water intake also results in astrocytic swelling that can contribute to motor impairment, but likely only in milder injuries. In severe rat SCI, a low abundance of AQP4-overexpressing astrocytes was found during the motor recovery phase. Our results suggest that severe rat contusion SCI is a better model to analyze AQP4 functions after SCI. We found that AQP4 increases in the chronic post-injury phase are associated with the development of pain-like behavior in SCI rats, while possible mechanisms underlying pain development may involve astrocytic swelling-induced glutamate release. In contrast, the formation and size of fluid-filled cavities occurring later after SCI does not appear to be affected by the extent of increased AQP4 levels. Therefore, the effect of therapeutic interventions targeting AQP4 will depend not only on the time interval after SCI or animal models, but also on the balance between protective role of increased AQP4 in hypoxia and deleterious effects of ongoing astrocytic swelling. PMID

Role of AQP4 Antibody Serostatus and its Prediction of Visual Outcome in Neuromyelitis Optica: A Systematic Review and Meta-Analysis.

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Lin, Nan; Liu, Qing; Wang, Xiaoyu; Ma, Jianmei; Li, Yuyuan

2017-01-01

Backgroud: Neuromyelitis optica (NMO) is an autoimmune inflammatory disorder, which is characterized by severe attacks of optic neuritis and myelitis. Antibodies (Ab) to aquaporin-4 (AQP4) (or NMO-IgG) as a serological biomarker of NMO have been widespread used. Nevertheless, some NMO patients remain seronegative for AQP4-Ab and/or have no detected optic nerve involvement. In addition, no consensus exists on the association between AQP4-Ab serostatus and visual outcome in NMO. To drive a more precise estimate of this postulated relationship, a metaanalysis was performed based on existing relevant studies. Studies were searched by PubMed and MEDLINE up to March 2016. Study quality was assessed, and meta-analysis was conducted using the RevMan 5.1. Odds ratios with 95% confidence interval were calculated and funnel plot was applied to assess the potential publication bias. In a total of 1288 relevant studies, 18 studies satisfied the eligibility criteria and were included in the systemic review. Only 9 studies appeared eligible for the meta-analysis, together including 624 AQP4-Ab-positive and 119 AQP4-Ab-negative NMO patients. The results revealed associations between AQP4-Ab seropositivity and visual impairment in NMO (OR, 3.16; 95% CI, 1.09, 9.19; P = 0.03). The results of subgroup analyses based on different methods of AQP-4 detection also showed significantly differences between AQP4-Ab seropositivity and visual impairment in NMO, especially in CBA subgroup. This meta-analysis indicates that AQP4-Ab serostatus has the positive with poor visual outcome in NMO. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Systems-level analysis of cell-specific AQP2 gene expression in renal collecting duct.

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Yu, Ming-Jiun; Miller, R Lance; Uawithya, Panapat; Rinschen, Markus M; Khositseth, Sookkasem; Braucht, Drew W W; Chou, Chung-Lin; Pisitkun, Trairak; Nelson, Raoul D; Knepper, Mark A

2009-02-17

We used a systems biology-based approach to investigate the basis of cell-specific expression of the water channel aquaporin-2 (AQP2) in the renal collecting duct. Computational analysis of the 5'-flanking region of the AQP2 gene (Genomatix) revealed 2 conserved clusters of putative transcriptional regulator (TR) binding elements (BEs) centered at -513 bp (corresponding to the SF1, NFAT, and FKHD TR families) and -224 bp (corresponding to the AP2, SRF, CREB, GATA, and HOX TR families). Three other conserved motifs corresponded to the ETS, EBOX, and RXR TR families. To identify TRs that potentially bind to these BEs, we carried out mRNA profiling (Affymetrix) in mouse mpkCCDc14 collecting duct cells, revealing expression of 25 TRs that are also expressed in native inner medullary collecting duct. One showed a significant positive correlation with AQP2 mRNA abundance among mpkCCD subclones (Ets1), and 2 showed a significant negative correlation (Elf1 and an orphan nuclear receptor Nr1h2). Transcriptomic profiling in native proximal tubules (PT), medullary thick ascending limbs (MTAL), and IMCDs from kidney identified 14 TRs (including Ets1 and HoxD3) expressed in the IMCD but not PT or MTAL (candidate AQP2 enhancer roles), and 5 TRs (including HoxA5, HoxA9 and HoxA10) expressed in PT and MTAL but not in IMCD (candidate AQP2 repressor roles). In luciferase reporter assays, overexpression of 3 ETS family TRs transactivated the mouse proximal AQP2 promoter. The results implicate ETS family TRs in cell-specific expression of AQP2 and point to HOX, RXR, CREB and GATA family TRs as playing likely additional roles.

Correlation between salivary secretion and salivary AQP5 levels in health and disease.

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Wang, Di; Iwata, Fusako; Muraguchi, Masahiro; Ooga, Keiko; Ohmoto, Yasukazu; Takai, Masaaki; Mori, Toyoki; Ishikawa, Yasuko

2009-01-01

Saliva samples are useful for noninvasive diagnosis of oral and systemic diseases. The water channel protein aquaporin-5 (AQP5) is released into human saliva. Salivary AQP5 levels show a diurnal variation with the secretion of high levels during the waking hours. An age-related decrease in salivary AQP5 levels parallels a decrease in the volume of saliva. Cevimeline, a muscarinic acetylcholine receptor (mAChR) agonist, induces the release of AQP5. Changes in salivary AQP5 levels after cevimeline administration occur simultaneously with changes in saliva flow rate. AQP5 and lipid rafts are released separately from human salivary glands upon M(3) mAChR stimulation. In patients with diabetes mellitus or Sjögren's syndrome, a decrease in salivary secretion occurs concomitantly with low salivary AQP5 levels. Salivary AQP5 levels correlate with salivary secretion in both healthy and disease states, suggesting that changes in salivary AQP5 levels can be used as an indicator of salivary flow rate and the effect of M(3) mAChR agonists on human salivary glands.

Acyrthosiphon pisum AQP2: a multifunctional insect aquaglyceroporin

Czech Academy of Sciences Publication Activity Database

Wallace, I. S.; Shakesby, A. J.; Hwang, J. H.; Choi, W. G.; Martínková, Natália; Douglas, A. E.; Roberts, D. M.

2012-01-01

Roč. 1818, č. 3 (2012), s. 627-635 ISSN 0005-2736 Institutional research plan: CEZ:AV0Z60930519 Keywords : aphid * Buchnera aphidicola * channel proteins * osmoregulation * phylogeny Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.389, year: 2012

Regulation and Function of AQP4 in the Central Nervous System

DEFF Research Database (Denmark)

Assentoft, Mette; Larsen, Brian Roland; MacAulay, Nanna

2015-01-01

Aquaporin 4 (AQP4) is the predominant water channel in the mammalian brain and is mainly expressed in the perivascular glial endfeet at the brain-blood interface. Based on studies on AQP4(-/-) mice, AQP4 has been assigned physiological roles in stimulus-induced K(+) clearance, paravascular fluid ...

Targeting Aquaporin Function : Potent Inhibition of Aquaglyceroporin-3 by a Gold-Based Compound

NARCIS (Netherlands)

Martins, Ana Paula; Marrone, Alessandro; Ciancetta, Antonella; Galan Cobo, Ana; Echevarria, Miriam; Moura, Teresa F.; Re, Nazzareno; Casini, Angela; Soveral, Graca

2012-01-01

Aquaporins (AQPs) are membrane channels that conduct water and small solutes such as glycerol and are involved in many physiological functions. Aquaporin-based modulator drugs are predicted to be of broad potential utility in the treatment of several diseases. Until today few AQP inhibitors have

Role of Aquaporin-4 in Airspace-to-Capillary Water Permeability in Intact Mouse Lung Measured by a Novel Gravimetric Method

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Song, Yuanlin; Ma, Tonghui; Matthay, Michael A.; Verkman, A.S.

2000-01-01

The mammalian peripheral lung contains at least three aquaporin (AQP) water channels: AQP1 in microvascular endothelia, AQP4 in airway epithelia, and AQP5 in alveolar epithelia. In this study, we determined the role of AQP4 in airspace-to-capillary water transport by comparing water permeability in wild-type mice and transgenic null mice lacking AQP1, AQP4, or AQP1/AQP4 together. An apparatus was constructed to measure lung weight continuously during pulmonary artery perfusion of isolated mouse lungs. Osmotically induced water flux (Jv) between the airspace and capillary compartments was measured from the kinetics of lung weight change in saline-filled lungs in response to changes in perfusate osmolality. Jv in wild-type mice varied linearly with osmotic gradient size (4.4 × 10−5 cm3 s−1 mOsm−1) and was symmetric, independent of perfusate osmolyte size, weakly temperature dependent, and decreased 11-fold by AQP1 deletion. Transcapillary osmotic water permeability was greatly reduced by AQP1 deletion, as measured by the same method except that the airspace saline was replaced by an inert perfluorocarbon. Hydrostatically induced lung edema was characterized by lung weight changes in response to changes in pulmonary arterial inflow or pulmonary venous outflow pressure. At 5 cm H2O outflow pressure, the filtration coefficient was 4.7 cm3 s−1 mOsm−1 and reduced 1.4-fold by AQP1 deletion. To study the role of AQP4 in lung water transport, AQP1/AQP4 double knockout mice were generated by crossbreeding of AQP1 and AQP4 null mice. Jv were (cm3 s−1 mOsm−1 × 10−5, SEM, n = 7–12 mice): 3.8 ± 0.4 (wild type), 0.35 ± 0.02 (AQP1 null), 3.7 ± 0.4 (AQP4 null), and 0.25 ± 0.01 (AQP1/AQP4 null). The significant reduction in P f in AQP1 vs. AQP1/AQP4 null mice was confirmed by an independent pleural surface fluorescence method showing a 1.6 ± 0.2-fold (SEM, five mice) reduced P f in the AQP1/AQP4 double knockout mice vs. AQP1 null mice. These results establish

Identification of the AQP members involved in abiotic stress responses from Arabidopsis.

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Feng, Zhi-Juan; Xu, Sheng-Chun; Liu, Na; Zhang, Gu-Wen; Hu, Qi-Zan; Xu, Zhao-Shi; Gong, Ya-Ming

2018-03-10

Aquaporins (AQPs) constitute a highly diverse family of water channel proteins that play crucial biological functions in plant growth and development and stress physiology. In Arabidopsis, 35 AQPs are classified into four subfamilies (PIPs, TIPs, NIPs and SIPs). However, knowledge about the roles of different subfamily AQPs remains limited. Here, we explored the chromosomal location, gene structure and expression patterns of all AQPs in different tissues or under different abiotic stresses based on available microarray data. Tissue expression analysis showed that different AQPs had various expression patterns in tissues (root, leaf, flower and seed). Expression profiles under stress conditions revealed that most AQPs were responsive to osmotic, salt and drought stresses. Phenotypic and physiological identification showed that Tip2;2 loss-of-function mutant exhibited less sensitive to abiotic stresses (mannitol, NaCl and PEG) compared with wild-type, as evident by analysis of germination rate, root growth, survival rate, ion leakage, malondialdehyde (MDA) and proline contents. Mutant of TIP2;2 modulated the transcript levels of SOS1, SOS2, SOS3, DREB1A, DREB2A and P5CS1, under abiotic stress conditions. This study provides a basis for further functional identification of stress-related candidate AQPs in Arabidopsis. Copyright © 2017 Elsevier B.V. All rights reserved.

Compartmentalization of Aquaporins in the Human Intestine

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Rajendram V. Rajnarayanan

2008-06-01

Full Text Available Improper localization of water channel proteins called aquaporins (AQP induce mucosal injury which is implicated in Crohn’s disease and ulcerative colitis. The amino acid sequences of AQP3 and AQP10 are 79% similar and belong to the mammalian aquaglyceroporin subfamily. AQP10 is localized on the apical compartment of the intestinal epithelium called the glycocalyx while AQP3 is selectively targeted to the basolateral membrane. Despite the high sequence similarity and evolutionary relatedness, the molecular mechanism involved in the polarity, selective targeting and function of AQP3 and AQP10 in the intestine is largely unknown. Our hypothesis is that the differential polarity and selective targeting of AQP3 and AQP10 in the intestinal epithelial cells is influenced by amino acid signal motifs. We performed sequence and structural alignments to determine differences in signals for localization and posttranslational glycosylation. The basolateral sorting motif “YRLL” is present in AQP3 but absent in AQP10; while Nglycosylation signals are present in AQP10 but absent in AQP3. Furthermore, the C-terminal region of AQP3 is longer compared to AQP10. The sequence and structural differences between AQP3 and AQP10 provide insights into the differential compartmentalization and function of these two aquaporins commonly expressed in human intestines.

Overexpression of the wheat aquaporin gene, TaAQP7, enhances drought tolerance in transgenic tobacco.

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Shiyi Zhou

Full Text Available Aquaporin (AQP proteins have been shown to transport water and other small molecules through biological membranes, which is crucial for plants to combat stress caused by drought. However, the precise role of AQPs in drought stress response is not completely understood in plants. In this study, a PIP2 subgroup gene AQP, designated as TaAQP7, was cloned and characterized from wheat. Expression of TaAQP7-GFP fusion protein revealed its localization in the plasma membrane. TaAQP7 exhibited high water channel activity in Xenopus laevis oocytes and TaAQP7 transcript was induced by dehydration, and treatments with polyethylene glycol (PEG, abscisic acid (ABA and H(2O(2. Further, TaAQP7 was upregulated after PEG treatment and was blocked by inhibitors of ABA biosynthesis, implying that ABA signaling was involved in the upregulation of TaAQP7 after PEG treatment. Overexpression of TaAQP7 increased drought tolerance in tobacco. The transgenic tobacco lines had lower levels of malondialdehyde (MDA and H(2O(2, and less ion leakage (IL, but higher relative water content (RWC and superoxide dismutase (SOD and catalase (CAT activities when compared with the wild type (WT under drought stress. Taken together, our results show that TaAQP7 confers drought stress tolerance in transgenic tobacco by increasing the ability to retain water, reduce ROS accumulation and membrane damage, and enhance the activities of antioxidants.

Expression of AQP3 gene in chronic atrophic and chronic superficial gastritis patients

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Shijun Zhang

2007-12-01

Full Text Available BACKGROUND: Most studies about aquaporin 3 (AQP3 in the gastrointestinal tract were carried out on both in vivo and in vitro. The role of AQP3-mediated water transport in human gastrointestinal tract is still unclear. Our aim in this study was to explore the expression of AQP3 gene in chronic atrophic gastritis (CAG and chronic superficial gastritis (CSG atients and to determine its possible function in the development of gastritis.
METHODS: Twenty-two outpatients diagnosed as CSG and 12 outpatients diagnosed as CAG were selected randomly. Ten cases of healthy individuals were selected as normal control group. In all cases, AQP3 gene expression of gastric mucosa was detected by fluorescence quantitative polymerase chain reaction (FQ-PCR.
RESULTS: The AQP3 gene expression was significantly higher in gastric mucosa of CSG and healthy individuals than that in CAG (P<0.01. However, there was no significant difference in the AQP3 gene expression between helicobacter pylori positive patients and helicobacter pylori negative patients (P>0.05.
CONCLUSIONS: AQP3 expression might play certain role in the occurrence and development of gastritis.
KEY WORDS: Aquaporin 3, chronic superficial gastritis, chronic atrophic gastritis.

Gene expression and localization of two types of AQP5 in Xenopus tropicalis under hydration and dehydration.

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Shibata, Yuki; Sano, Takahiro; Tsuchiya, Nobuhito; Okada, Reiko; Mochida, Hiroshi; Tanaka, Shigeyasu; Suzuki, Masakazu

2014-07-01

Two types of aquaporin 5 (AQP5) genes (aqp-xt5a and aqp-xt5b) were identified in the genome of Xenopus tropicalis by synteny comparison and molecular phylogenetic analysis. When the frogs were in water, AQP-xt5a mRNA was expressed in the skin and urinary bladder. The expression of AQP-xt5a mRNA was significantly increased in dehydrated frogs. AQP-xt5b mRNA was also detected in the skin and increased in response to dehydration. Additionally, AQP-xt5b mRNA began to be slightly expressed in the lung and stomach after dehydration. For the pelvic skin of hydrated frogs, immunofluorescence staining localized AQP-xt5a and AQP-xt5b to the cytoplasm of secretory cells of the granular glands and the apical plasma membrane of secretory cells of the small granular glands, respectively. After dehydration, the locations of both AQPs in their respective glands did not change, but AQP-xt5a was visualized in the cytoplasm of secretory cells of the small granular glands. For the urinary bladder, AQP-xt5a was observed in the apical plasma membrane and cytoplasm of a number of granular cells under normal hydration. After dehydration, AQP-xt5a was found in the apical membrane and cytoplasm of most granular cells. Injection of vasotocin into hydrated frogs did not induce these changes in the localization of AQP-xt5a in the small granular glands and urinary bladder, however. The results suggest that AQP-xt5a might be involved in water reabsorption from the urinary bladder during dehydration, whereas AQP-xt5b might play a role in water secretion from the small granular gland. Copyright © 2014 the American Physiological Society.

Highly selective water channel activity measured by voltage clamp: analysis of planar lipid bilayers reconstituted with purified AqpZ.

Science.gov (United States)

Pohl, P; Saparov, S M; Borgnia, M J; Agre, P

2001-08-14

Aquaporins are membrane channels selectively permeated by water or water plus glycerol. Conflicting reports have described ion conductance associated with some water channels, raising the question of whether ion conductance is a general property of the aquaporin family. To clarify this question, a defined system was developed to simultaneously measure water permeability and ion conductance. The Escherichia coli water channel aquaporin-Z (AqpZ) was studied, because it is a highly stable tetramer. Planar lipid bilayers were formed from unilamellar vesicles containing purified AqpZ. The hydraulic conductivity of bilayers made from the total extract of E. coli lipids increased 3-fold if reconstituted with AqpZ, but electric conductance was unchanged. No channel activity was detected under voltage-clamp conditions, indicating that less than one in 10(9) transport events is electrogenic. Microelectrode measurements were simultaneously undertaken adjacent to the membrane. Changes in sodium concentration profiles accompanying transmembrane water flow permitted calculation of the activation energies: 14 kcal/mol for protein-free lipid bilayers and 4 kcal/mol for lipid bilayers containing AqpZ. Neither the water permeability nor the electric conductivity exhibited voltage dependence. This sensitive system demonstrated that AqpZ is permeated by water but not charged ions and should permit direct analyses of putative electrogenic properties of other aquaporins.

AQP4 expression and its relationship with brain edema after gamma kife radiosurgery in rats

International Nuclear Information System (INIS)

Shen Guangjian; Xu Minhui; Zou Yongwen; Gen Mingying; Li Feipeng; Tang Wenyuan; Sun Shanquan

2007-01-01

Objective: To explore AQP4 expression and its relationship with brain edema after gamma knife radiosurgery (GKRS) in rats. Methods: Wistar rats were divided into two groups-the control group and experimental group. The experimental group model was established by radiating rat left rotral caudate nucleus with GKRS (100 Gy, 4 mm), and was examinded at interval times of 1 d, 3 d, 7 d, 15 d, 30 d and 45 d. Brain water content (BWC) was determined by wet-dry weighing method. AQP4 expression on mRNA and protein were measured by immunohistochemistry (ICH) and in situ hybridization (ISH). Results: In control group, AQP4 protein and its mRNA were expressed in subpial astrocytes, choroid plexus, ependyma and perivascular astrocytes. After GKRS, AQP4 protein and its mRNA in these sites were enhanced, and became most remarkable at 30 d. The positive corrlationship was showed between AQP4 and its mRNA, and AQP4 and BWC. Conclusions: AQP4 protein and its mRNA can be induced in some brain zone after irradiating rat left rotral caudate nucleus with GKRS. The increased expression of AQP4 and its mRNA may play a role in the ocurrence or development of brain edema after GKRS. (authors)

The Arg233Lys AQP0 mutation disturbs aquaporin0-calmodulin interaction causing polymorphic congenital cataract.

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Shanshan Hu

Full Text Available Calmodulin (CaM directly interacts with the aquaporin 0 (AQP0 C-terminus in a calcium dependent manner to regulate the water permeability of AQP0. We previously identified a missense mutation (p.R233K in the putative CaM binding domain of AQP0 C-terminus in a congenital cataract family. This study was aimed at exploring the potential pathogenesis of this mutation causative of cataract and mainly identifying how it influenced the binding of AQP0 to CaM. Wild type and R233K mutant AQP0 with EGFP-tag were transfected separately into Hela cells to determine the expression and subcellular localizations. The co-immunoprecipitation (CoIP assay was used to detect the interaction between AQP0 and CaM. AQP0 C-terminus peptides were synthesized with and without R233K, and the binding abilities of these peptides to CaM were assessed using a fluorescence binding assay. Localizations of wild type and R233K mutant AQP0 were determined from EGFP fluorescence, and the chimeric proteins were both localized abundantly in the plasma membrane. Protein expression levels of the culture cells showed no significant difference between them. The results from CoIP assay implied that R233K mutant presented more weakly in association with CaM than wild type AQP0. The AQP0 C-terminal mutant peptide was found to have 2.5-fold lower binding affinity to CaM than wild type peptide. These results suggested that R233K mutation did not affect the expression, location and trafficking of the protein but did influence the interaction between AQP0 and CaM. The binding affinity of AQP0 C-terminus to CaM was significantly reduced. Due to lack of the modulation of the Ca2+-calmodulin complex, the water permeability of AQP0 was subsequently augmented, which might lead to the development of this cataract.

New Perspectives on the Potential Role of Aquaporins (AQPs in the Physiology of Inflammation

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Rosaria Meli

2018-02-01

Full Text Available Aquaporins (AQPs are emerging, in the last few decades, as critical proteins regulating water fluid homeostasis in cells involved in inflammation. AQPs represent a family of ubiquitous membrane channels that regulate osmotically water flux in various tissues and sometimes the transport of small solutes, including glycerol. Extensive data indicate that AQPs, working as water channel proteins, regulate not only cell migration, but also common events essential for inflammatory response. The involvement of AQPs in several inflammatory processes, as demonstrated by their dysregulation both in human and animal diseases, identifies their new role in protection and response to different noxious stimuli, including bacterial infection. This contribution could represent a new key to clarify the dilemma of host-pathogen communications, and opens up new scenarios regarding the investigation of the modulation of specific AQPs, as target for new pharmacological therapies. This review provides updated information on the underlying mechanisms of AQPs in the regulation of inflammatory responses in mammals and discusses the broad spectrum of options that can be tailored for different diseases and their pharmacological treatment.

Effects of glyceryl glucoside on AQP3 expression, barrier function and hydration of human skin.

Science.gov (United States)

Schrader, A; Siefken, W; Kueper, T; Breitenbach, U; Gatermann, C; Sperling, G; Biernoth, T; Scherner, C; Stäb, F; Wenck, H; Wittern, K-P; Blatt, T

2012-01-01

Aquaporins (AQPs) present in the epidermis are essential hydration-regulating elements controlling cellular water and glycerol transport. In this study, the potential of glyceryl glucoside [GG; alpha-D-glucopyranosyl-alpha-(1->2)-glycerol], an enhanced glycerol derivative, to increase the expression of AQP3 in vitro and ex vivo was evaluated. In vitro studies with real-time RT-PCR and FACS measurements were performed to test the induction by GG (3% w/v) of AQP3 mRNA and protein in cultured human keratinocytes. GG-containing formulations were applied topically to volunteer subjects and suction blister biopsies were analyzed to assess whether GG (5%) could penetrate the epidermis of intact skin, and subsequently upregulate AQP3 mRNA expression and improve barrier function. AQP3 mRNA and protein levels were significantly increased in cultured human keratinocytes. In the studies on volunteer subjects, GG significantly increased AQP3 mRNA levels in the skin and reduced transepidermal water loss compared with vehicle-controlled areas. GG promotes AQP3 mRNA and protein upregulation and improves skin barrier function, and may thus offer an effective treatment option for dehydrated skin. Copyright © 2012 S. Karger AG, Basel.

Phosphorylation of human aquaporin 2 (AQP2) allosterically controls its interaction with the lysosomal trafficking protein LIP5.

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Roche, Jennifer Virginia; Survery, Sabeen; Kreida, Stefan; Nesverova, Veronika; Ampah-Korsah, Henry; Gourdon, Maria; Deen, Peter M T; Törnroth-Horsefield, Susanna

2017-09-01

The interaction between the renal water channel aquaporin-2 (AQP2) and the lysosomal trafficking regulator-interacting protein LIP5 targets AQP2 to multivesicular bodies and facilitates lysosomal degradation. This interaction is part of a process that controls AQP2 apical membrane abundance in a vasopressin-dependent manner, allowing for urine volume adjustment. Vasopressin regulates phosphorylation at four sites within the AQP2 C terminus (Ser 256 , Ser 261 , Ser 264 , and Thr 269 ), of which Ser 256 is crucial and sufficient for AQP2 translocation from storage vesicles to the apical membrane. However, whether AQP2 phosphorylation modulates AQP2-LIP5 complex affinity is unknown. Here we used far-Western blot analysis and microscale thermophoresis to show that the AQP2 binds LIP5 in a phosphorylation-dependent manner. We constructed five phospho-mimicking mutants (S256E, S261E, S264E, T269E, and S256E/T269E) and a C-terminal truncation mutant (ΔP242) that lacked all phosphorylation sites but retained a previously suggested LIP5-binding site. CD spectroscopy indicated that wild-type AQP2 and the phospho-mimicking mutants had similar overall structure but displayed differences in melting temperatures possibly arising from C-terminal conformational changes. Non-phosphorylated AQP2 bound LIP5 with the highest affinity, whereas AQP2-ΔP242 had 20-fold lower affinity as determined by microscale thermophoresis. AQP2-S256E, S261E, T269E, and S256E/T269E all had reduced affinity. This effect was most prominent for AQP2-S256E, which fits well with its role in apical membrane targeting. AQP2-S264E had affinity similar to non-phosphorylated AQP2, possibly indicating a role in exosome excretion. Our data suggest that AQP2 phosphorylation allosterically controls its interaction with LIP5, illustrating how altered affinities to interacting proteins form the basis for regulation of AQP2 trafficking by post-translational modifications. © 2017 by The American Society for

Expression of aquaporin 3 in gills of the Atlantic killifish (Fundulus heteroclitus): Effects of seawater acclimation

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Jung, Dawoon; Sato, J. Denry; Shaw, Joseph R.; Stanton, Bruce A.

2011-01-01

Estuarine fish, such as the Atlantic killifish (Fundulus heteroclitus), are constantly and rapidly exposed to changes in salinity. Although ion transport in killifish gills during acclimation to increased salinity has been studied extensively, no studies have examined the role of aquaglyceroporin 3 (AQP3), a water, glycerol, urea, and ammonia transporter, during acclimation to increased salinity in this sentinel environmental model organism. The goal of this study was to test the hypothesis that transfer from freshwater to seawater decreases AQP3 gene and protein expression in the gill of killifish. Transfer from freshwater to seawater decreased AQP3 mRNA in the gill after 1 day, but had no effect on total gill AQP3 protein abundance as determined by western blot. Quantitative confocal immunocytochemistry confirmed western blot studies that transfer from freshwater to seawater did not change total AQP3 abundance in the gill; however, immunocytochemistry revealed that the amount of AQP3 in pillar cells of secondary lamellae decreased in seawater fish, whereas the amount of AQP3 in mitochondrion rich cells (MRC) in primary filaments of the gill increased in seawater fish. This response of AQP3 expression is unique to killifish compared to other teleosts. Although the role of AQP3 in the gill of killifish has not been completely elucidated, these results suggest that AQP3 may play an important role in the ability of killifish to acclimate to increased salinity. PMID:22193757

Molecular cloning and expression analysis of the aqp1aa gene in half-smooth tongue sole (Cynoglossus semilaevis.

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Hua Guo

Full Text Available Aquaporin 1 (AQP1 is a member of the transmembrane water channel family of proteins with special structural features, and two AQP1 paralogous genes (aqp1aa and aqp1ab are reported in teleosts. In the present study, the aqp1aa gene of half-smooth tongue sole (Cynoglossus semilaevis was cloned and characterized. The full-length cDNA of aqp1aa is 1411 bp with a 786 bp open reading frame encoding a 261-amino acid putative protein with a characteristic structure consisting of 6 membrane-spanning α-helical domains and two highly conserved asparagine-proline-alanine motifs. Real-time quantitative PCR revealed that aqp1aa mRNA is expressed predominantly in the testis of males and pseudo-males, while its expression is low in the ovary and lowest in doublesex and mab-3-related transcription factor 1(DMRT1 knock out fish and triploid males. In situ hybridization indicated that aqp1aa mRNA is expressed mainly in the germ cells of males and pseudo-males, especially in spermatozoa and spermatids. These results suggest that the aqp1aa may play a role in spermatogenesis of C. semilaevis.

Autoantibody-induced internalization of CNS AQP4 water channel and EAAT2 glutamate transporter requires astrocytic Fc receptor.

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Hinson, Shannon R; Clift, Ian C; Luo, Ningling; Kryzer, Thomas J; Lennon, Vanda A

2017-05-23

Aquaporin-4 (AQP4) water channel-specific IgG distinguishes neuromyelitis optica (NMO) from multiple sclerosis and causes characteristic immunopathology in which central nervous system (CNS) demyelination is secondary. Early events initiating the pathophysiological outcomes of IgG binding to astrocytic AQP4 are poorly understood. CNS lesions reflect events documented in vitro following IgG interaction with AQP4: AQP4 internalization, attenuated glutamate uptake, intramyelinic edema, interleukin-6 release, complement activation, inflammatory cell recruitment, and demyelination. Here, we demonstrate that AQP4 internalization requires AQP4-bound IgG to engage an astrocytic Fcγ receptor (FcγR). IgG-lacking Fc redistributes AQP4 within the plasma membrane and induces interleukin-6 release. However, AQP4 endocytosis requires an activating FcγR's gamma subunit and involves astrocytic membrane loss of an inhibitory FcγR, CD32B. Interaction of the IgG-AQP4 complex with FcγRs triggers coendocytosis of the excitatory amino acid transporter 2 (EAAT2). Requirement of FcγR engagement for internalization of two astrocytic membrane proteins critical to CNS homeostasis identifies a complement-independent, upstream target for potential early therapeutic intervention in NMO.

Homozygosity for aquaporin 7 G264V in three unrelated children with hyperglyceroluria and a mild platelet secretion defect.

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Goubau, Christophe; Jaeken, Jaak; Levtchenko, Elena N; Thys, Chantal; Di Michele, Michela; Martens, Geert A; Gerlo, Erik; De Vos, Rita; Buyse, Gunnar M; Goemans, Nathalie; Van Geet, Chris; Freson, Kathleen

2013-01-01

Aquaporin 7 (AQP7) belongs to the aquaglyceroporin family, which transports glycerol and water. AQP7-deficient mice develop obesity, insulin resistance, and hyperglyceroluria. However, AQP7's pathophysiologic role in humans is not yet known. Three children with psychomotor retardation and hyperglyceroluria were screened for AQP7 mutations. The children were from unrelated families. Urine and plasma glycerol levels were measured using a three-step enzymatic approach. Platelet morphology and function were studied using electron microscopy, aggregations, and adenosine triphosphate (ATP) secretion tests. The index patients were homozygous for AQP7 G264V, which has previously been shown to inhibit transport of glycerol in Xenopus oocytes. We also detected a subclinical platelet secretion defect with reduced ATP secretion, and the absence of a secondary aggregation wave after epinephrine stimulation. Electron microscopy revealed round platelets with centrally located granules. Immunostaining showed AQP7 colocalization, with dense granules that seemed to be released after strong platelet activation. Healthy relatives of these patients, who were homozygous (not heterozygous) for G264V, also had hyperglyceroluria and platelet granule abnormalities. The discovery of an association between urine glycerol loss and a platelet secretion defect is a novel one, and our findings imply the involvement of AQPs in platelet secretion. Additional studies are needed to define whether AQP7 G264V is also a risk factor for mental disability.

Hormonal regulation of aquaporin 3: opposing actions of prolactin and cortisol in tilapia gill.

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Breves, Jason P; Inokuchi, Mayu; Yamaguchi, Yoko; Seale, Andre P; Hunt, Bethany L; Watanabe, Soichi; Lerner, Darren T; Kaneko, Toyoji; Grau, E Gordon

2016-09-01

Aquaporins (Aqps) are expressed within key osmoregulatory tissues where they mediate the movement of water and selected solutes across cell membranes. We leveraged the functional plasticity of Mozambique tilapia (Oreochromis mossambicus) gill epithelium to examine how Aqp3, an aquaglyceroporin, is regulated in response to osmoregulatory demands. Particular attention was paid to the actions of critical osmoregulatory hormones, namely, prolactin (Prl), growth hormone and cortisol. Branchial aqp3 mRNA levels were modulated following changes in environmental salinity, with enhanced aqp3 mRNA expression upon transfer from seawater to freshwater (FW). Accordingly, extensive Aqp3 immunoreactivity was localized to cell membranes of branchial epithelium in FW-acclimated animals. Upon transferring hypophysectomized tilapia to FW, we identified that a pituitary factor(s) is required for Aqp3 expression in FW. Replacement with ovine Prl (oPrl) was sufficient to stimulate Aqp3 expression in hypophysectomized animals held in FW, an effect blocked by coinjection with cortisol. Both oPrl and native tilapia Prls (tPrl177 and tPrl188) stimulated aqp3 in incubated gill filaments in a concentration-related manner. Consistent with in vivo responses, coincubation with cortisol blocked oPrl-stimulated aqp3 expression in vitro Our data indicate that Prl and cortisol act directly upon branchial epithelium to regulate Aqp3 in tilapia. Thus, within the context of the diverse actions of Prl on hydromineral balance in vertebrates, we define a new role for Prl as a regulator of Aqp expression. © 2016 Society for Endocrinology.

Maximal Oxygen Consumption is Reduced in Aquaporin-1 Knockout Mice

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Samer Al-Samir

2016-08-01

Full Text Available We have measured maximal oxygen consumption (V’O2,max of mice lacking one or two of the established mouse red-cell CO2 channels AQP1, AQP9 and Rhag. We intended to study whether these proteins, by acting as channels for O2, determine O2 exchange in the lung and in the periphery. We found that V’O2,max as determined by the Helox technique is reduced by ~ 16%, when AQP1 is knocked out, but not when AQP9 or Rhag are lacking. This figure holds for animals respiring normoxic as well as hypoxic gas mixtures. To see whether the reduction of V’O2,max is due to impaired O2 uptake in the lung, we measured carotid arterial O2 saturation (SO2 by pulse oximetry. Neither under normoxic (inspiratory O2 21% nor under hypoxic conditions (11% O2 is there a difference in SO2 between AQP1null and WT mice, suggesting that AQP1 is not critical for O2 uptake in the lung. The fact that the % reduction of V’O2,max is identical in normoxia and hypoxia indicates moreover that the limitation of V’O2,max is not due to an O2 diffusion problem, neither in the lung nor in the periphery. Instead, it appears likely that AQP1null animals exhibit a reduced V’O2,max due to the reduced wall thickness and muscle mass of the left ventricles of their hearts, as reported previously. We conclude that very likely the properties of the hearts of AQP1 knockout mice cause a reduced maximal cardiac output and thus cause a reduced V’O2,max, which constitutes a new phenotype of these mice.

Correlation between AQP4 mRNA and PKC activity after gamma knife radiosurgery in rat brain

International Nuclear Information System (INIS)

Shen Guangjian; Xu Minhui; Gen Mingying; Tang Wenyuan; Sun Shanquan

2009-01-01

Objective: To explore the change of AQP4 mRNA expression and the correlation with PKC in rat brain irradiated by γ knife radiosurgery (GKS). Methods: 30 Wistar rats were used in the study. The experimental radiosurgery model was established by radiating rat left rotral caudate nucleus with GKS(one target, 100 Gy in isocenter dose and 4 mm in collimator), and was examined at 1,3,7,15,30 and 45 d post-irradiation. AQP4 mRNA expression, PKC activity and free intracellular calcium ion concentration ([Ca 2+ ] i ) of brain tissue were determined by RT-PCR, liquid scintillation counter and Fura-2/AM, respectively. Results: AQP4 mRNA expression increased gradually from 0.99 ± 0.05 in control group to 2.32 ± 0.10 at 30 d post-irradiation, and decreased to 2.21 ± 0.08 at 45 d post-irradiation. The PKC activity and the free [Ca 2+ ] i decreased gradually from 0.5896 ± 0.2101 and 455.82 ± 20.13 in control group to 0.0404 ± 0.0294 and 196.72 ± 9.87 at 30 d post- irradiation, and increased to 0.1050 ± 0.0607 and 219.26 ± 10.43 at 45 d post-irradiation, respectively. The significant differences were found between experimental group and control group except at 1 d post-irradiation (P 2+ ] i and the PKC activity was positive (P=0.001, r=0.959). Conclusions: The increased expression of AQP4 mRNA might result from the inhibition of PKC activity due to the reduction of free [Ca 2+ ] i after GKS. (authors)

[Effect of Zhenwu Tang on regulating of "AVP-V2R-AQP2" pathway in NRK-52E cells].

Science.gov (United States)

Zhou, Xiao-Jie; Bao, Yu-Ting; Chen, Hong-Shu; Xuan, Ling; Chen, Xue-Ming; Zhang, Jie-Ying; Yang, Yuan-Xiao; Li, Chang-Yu

2018-02-01

This study was aimed to investigate the effect and mechanism of Zhenwu Tang on AVP-V2R-AQP2 pathway in NRK-52E cells in vitro . Forty eight male SD rats were randomly divided into eight groups with 6 animals in each group. Distilled water or 22.68 g·kg⁻¹·d⁻¹ Zhenwu Tang(calculated by raw drug dosage meter) was given by gavage. Blood samples were collected by cardiac puncture， and the medicated serum was centrifuged from the blood by 3 000 r·min⁻¹. NRK-52E cells were treated with different medicated serum or dDAVP. The condition of cell proliferation was detected by RTCA. The distribution of V2R and AQP2 in cells were detected by immunofluorescence. The expression of V2R， PKA and AQP2 were detected by Western blot and AQP2 mRNA level was detected by real-time PCR. Results showed that the level of AQP2 mRNA( P Tang medicated serum for 24 h were significantly higher than that of normal rat serum group. And the expression level of V2R， p-AQP2 and AQP2( P Tang medicated serum could increase the expression level of V2R， PKA and AQP2 which exist in AVP-V2R-AQP2 pathway in NRK-52E， and there is synergistic effect between Zhenwu Tang medicated serum and dDAVP. So the pathway of AVP-V2R-AQP2 may be one of the mechanism for which Zhenwu Tang regulate balance of water transportation. Copyright© by the Chinese Pharmaceutical Association.

NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression

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Guo, Kai, E-mail: gk161@163.com [Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Department of Respiration, 161th Hospital, PLA, Wuhan 430015 (China); Jin, Faguang, E-mail: jinfag@fmmu.edu.cn [Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China)

2015-09-25

The osmoregulated transcription factor nuclear factor of activated T-cells 5(NFAT5), has been found to play important roles in the development of many kinds of human cancers, including breast cancer, colon carcinoma, renal cell carcinoma and melanoma. The aim of the present study was to determine whether NFAT5 is involved in the proliferation and migration of lung adenocarcinoma cells. We found that NFAT5 was upregulated in lung adenocarcinoma cells and knockdown of NFAT5 decreased proliferation and migration of the cells, accompanied by a significant reduction in the expression of AQP5. AQP5 was upregulated in lung adenocarcinoma cells and knockdown of AQP5 also inhibited proliferation and migration of the cells as knockdown of NFAT5 did. Moreover, overexpression of NFAT5 promoted proliferation and migration of lung adenocarcinoma cells, accompanied by a significant increase in the expression of AQP5. These results indicate that NFAT5 plays important roles in proliferation and migration of human lung adenocarcinoma cells through regulating AQP5 expression, providing a new therapeutic option for lung adenocarcinoma therapy. - Highlights: • NFAT5 expression is higher in lung adenocarcinoma cells compared with normal cells. • NFAT5 knockdown decreases proliferation and migration of lung adenocarcinoma cells. • Knockdown of NFAT5 reduces AQP5 expression in human lung adenocarcinoma cells. • Overexpression of NFAT5 promotes proliferation and migration of lung adenocarcinoma cells. • Overexpression of NFAT5 increases AQP5 expression in human lung adenocarcinoma cells.

NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression

International Nuclear Information System (INIS)

Guo, Kai; Jin, Faguang

2015-01-01

The osmoregulated transcription factor nuclear factor of activated T-cells 5(NFAT5), has been found to play important roles in the development of many kinds of human cancers, including breast cancer, colon carcinoma, renal cell carcinoma and melanoma. The aim of the present study was to determine whether NFAT5 is involved in the proliferation and migration of lung adenocarcinoma cells. We found that NFAT5 was upregulated in lung adenocarcinoma cells and knockdown of NFAT5 decreased proliferation and migration of the cells, accompanied by a significant reduction in the expression of AQP5. AQP5 was upregulated in lung adenocarcinoma cells and knockdown of AQP5 also inhibited proliferation and migration of the cells as knockdown of NFAT5 did. Moreover, overexpression of NFAT5 promoted proliferation and migration of lung adenocarcinoma cells, accompanied by a significant increase in the expression of AQP5. These results indicate that NFAT5 plays important roles in proliferation and migration of human lung adenocarcinoma cells through regulating AQP5 expression, providing a new therapeutic option for lung adenocarcinoma therapy. - Highlights: • NFAT5 expression is higher in lung adenocarcinoma cells compared with normal cells. • NFAT5 knockdown decreases proliferation and migration of lung adenocarcinoma cells. • Knockdown of NFAT5 reduces AQP5 expression in human lung adenocarcinoma cells. • Overexpression of NFAT5 promotes proliferation and migration of lung adenocarcinoma cells. • Overexpression of NFAT5 increases AQP5 expression in human lung adenocarcinoma cells

There is less MRI brain lesions and no characteristic MRI Brain findings in IIDDs patients with positive AQP4 serology among Malaysians.

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Abdullah, Suhailah; Fadzli, Farhana; Ramli, Norlisah; Tan, Chong Tin

2017-02-01

The recently introduced International Consensus diagnostic criteria for diagnosis of neuromyelitis spectrum disorder include patients who are seronegative for AQP4 antibody. The criteria are dependent on typical MRI changes in the spinal cord, optic nerve and brain. This study aims to determine whether there are significant differences in the MRI brain images between AQP4 positive and negative patients with IIDDs. MRI brain of patients with a diagnosis of IIDDs presented to the Hospital from 2010 to 2015 was analysed. The MRI was assessed by 2 radiologists blinded to the AQP4 status, on features said to be typical of NMOSD and MS. Thirty nine patients fulfilled the criteria and were included in the study. They consisted of 19 AQP4 seropositive and 20 AQP4 seronegative patients. The mean age was older (37.0 vs. 28.8 years) among the AQP4 positive group. The majority of the patients were ethnic Chinese (72%), followed by the Malays and Indians. Those with AQP4 seropositive status generally has less brain lesions, and significantly less fulfilling the McDonald DIS criteria as compared to those with AQP4 seronegative status (15.8% vs. 60.0%, p=0.005). None of the seven cerebral MRI features highlighted in NMOSD 2015 diagnostic criteria, said to be characteristic of NMOSD was more common among the AQP4 positive patients. These features were in fact seen less frequently among the AQP4 seropositive patients. An example was the extensive hemispheric lesion seen in 10.5% of AQP4 seropositive patients vs. 45% of that AQP4 seronegative group. There was no characteristic MRI brain features in the Malaysian AQP4 seropositive IIDD patients versus those who are seronegative. This could be a reflection of ethnical difference. Copyright © 2017 Elsevier B.V. All rights reserved.

Urinary KIM-1 and AQP-1 in patients with clear renal cell carcinoma: Potential noninvasive biomarkers

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Mijušković Mirjana

2016-01-01

Full Text Available Background/Aim. Kidney injury molecule-1 (KIM-1 and aquaporin-1 (AQP-1 are potential early urinary biomarkers of clear renal cell carcinoma (cRCC. The aim of this study was to ascertain relationship between the urine concentrations KIM-1 and AQP-1 with tumor size, grade, pT stage and type of operation (radical or partial nephrectomy in patients with cRCC. Methods. Urinary concentrations of urinary KIM-1 (uKIM-1 and urinary AQP-1 (uAQP-1 were determined by commercially available ELISA kits. The analysis included 40 patients undergoing partial or radical nephrectomy for cRCC and 40 age- and sex-matched healthy adult volunteers. Results. The median preoperative concentrations of KIM-1 in the cRCC group [0.724 ± 1.120 ng/mg urinary creatinine (Ucr] were significantly greater compared with controls (healthy volunteers (0.210 ± 0.082 ng/mgUcr (p = 0.0227. Postoperatively, uKIM-1 concentration decreased significantly to control values (0.177 ± 0.099 ng/mgUcr vs 0.210 ± 0.082 ng/mgUcr, respectively. The size, grade and stage of tumor were correlated positively with preoperative uKIM-1 concentrations. Contrary to these results, concentrations of uAQP-1 in the cRCC group were significantly lower (0.111 ± 0.092 ng/mgUcr compared with the control group (0.202 ± 0.078 ng/mgUcr (p = 0.0014. Postoperatively, the concentrations of uAQP-1 increased progressively up to control values, approximately. We find no significant correlation between preoperative uAQP-1 concentrations and tumor size, grade and stage. Conclusion. uKIM-1 was found to be a reliable diagnostic marker of cRCC, based on its significantly increased values before and decreased values after the nephrectomy. [Projekat Ministarstva nauke Republike Srbije, br. III41018

Endocrinopathies in paediatric-onset neuromyelitis optica spectrum disorder with aquaporin 4 (AQP4) antibody.

Science.gov (United States)

Hacohen, Yael; Messina, Silvia; Gan, Hoong-Wei; Wright, Sukhvir; Chandratre, Saleel; Leite, Maria Isabel; Fallon, Penny; Vincent, Angela; Ciccarelli, Olga; Wassmer, Evangeline; Lim, Ming; Palace, Jacqueline; Hemingway, Cheryl

2018-04-01

The involvement of the diencephalic regions in neuromyelitis optica spectrum disorder (NMOSD) may lead to endocrinopathies. In this study, we identified the following endocrinopathies in 60% (15/25) of young people with paediatric-onset aquaporin 4-Antibody (AQP4-Ab) NMOSD: morbid obesity ( n = 8), hyperinsulinaemia ( n = 5), hyperandrogenism ( n = 5), amenorrhoea ( n = 5), hyponatraemia ( n = 4), short stature ( n = 3) and central hypothyroidism ( n = 2) irrespective of hypothalamic lesions. Morbid obesity was seen in 88% (7/8) of children of Caribbean origin. As endocrinopathies were prevalent in the majority of paediatric-onset AQP4-Ab NMOSD, endocrine surveillance and in particular early aggressive weight management is required for patients with AQP4-Ab NMOSD.

Involvement of TRPV1 and AQP2 in hypertonic stress by xylitol in odontoblast cells.

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Tokuda, M; Fujisawa, M; Miyashita, K; Kawakami, Y; Morimoto-Yamashita, Y; Torii, M

2015-02-01

To examine the responses of mouse odontoblast-lineage cell line (OLC) cultures to xylitol-induced hypertonic stress. OLCs were treated with xylitol, sucrose, sorbitol, mannitol, arabinose and lyxose. Cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium assay. The expression of transient receptor potential vanilloids (TRPV) 1, 3 and 4 was detected using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay. The expression of aquaporin (AQP) 2 was detected using immunofluorescence and Western blotting analysis. The expression of interleukin-6 (IL-6) under xylitol-induced hypertonic stress was assessed using an enzyme-linked immunosorbent assay (ELISA). Small interfering ribonucleic acid (siRNA) for AQP-2 was used to inhibition assay. Xylitol-induced hypertonic stress did not decrease OLC viability, unlike the other sugars tested. OLCs expressed TRPV1, 3 and 4 as well as AQP2. Xylitol inhibited lipopolysaccharide (LPS)-induced IL-6 expression after 3 h of hypertonic stress. TRPV1 mRNA expression was upregulated by xylitol. Costimulation with HgCl2 (AQP inhibitor) and Ruthenium red (TRPV1 inhibitor) decreased cell viability with xylitol stimulation. OLCs treated with siRNA against TRPV1 exhibited decreased cell viability with xylitol stimulation. OLCs have high-cell viability under xylitol-induced hypertonic stress, which may be associated with TRPV1 and AQP2 expressions.

AQP4 plasma membrane trafficking or channel gating is not significantly modulated by phosphorylation at C-terminal serine residues

DEFF Research Database (Denmark)

Assentoft, Mette; Larsen, Brian R; Olesen, Emma T B

2014-01-01

heterologous expression in Xenopus laevis oocytes (along with serine-to-aspartate mutants of the same residues to mimic a phosphorylation). None of the mutant AQP4 constructs displayed alterations in the unit water permeability. Thus phosphorylation of six different serine residues in the COOH terminus of AQP4....... Phosphorylation of aquaporins can regulate plasma membrane localization and, possibly, the unit water permeability via gating of the AQP channel itself. In vivo phosphorylation of six serine residues in the COOH terminus of AQP4 has been detected by mass spectrometry: Ser(276), Ser(285), Ser(315), Ser(316), Ser...

Disruption of cyclooxygenase-2 prevents downregulation of cortical AQP2 and AQP3 in response to bilateral ureteral obstruction in the mouse

DEFF Research Database (Denmark)

Nilsson, Line; Madsen, Kirsten Morill; Topcu, Sukru Oguzkan

2012-01-01

Bilateral ureteral obstruction (BUO) in rats is associated with increased cyclooxygenase type 2 (COX-2) expression, and selective COX-2 inhibition prevents downregulation of aquaporins (AQPs) in response to BUO. It was hypothesized that a murine model would display similar changes in renal COX-2 ...

Pituitary Gonadotropins, Prolactin and Growth Hormone Differentially Regulate AQP1 Expression in the Porcine Ovarian Follicular Cells

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Mariusz T. Skowronski

2017-12-01

Full Text Available The present in vitro study analyzed whether the hormones that affect the ovarian follicular steroidogenesis process also participate in the regulation of AQP1 mRNA and protein expression. Granulosa (Gc and theca cells (Tc of medium and large porcine ovarian follicles were exposed to follicle-stimulating hormone (FSH, luteinizing hormone (LH, prolactin (PRL and growth hormone (GH for 24 h in separated cells and co-cultures of these cells. Real-time PCR, Western blotting, immunofluorescence and volumetric analysis were then performed. Gonadotropins, PRL and GH had a stimulatory impact on AQP1 mRNA and protein expression in Gc and Tc of medium and large ovarian cells. Moreover, swelling assays, in response to a hypotonic environment, demonstrated the functional presence of AQPs in porcine Gc and Tc. Immunofluorescence analysis showed that AQP1 protein was mainly localized in the perinuclear region of the cytoplasm, endosomes and cell membranes of Gc and Tc from medium and large follicles. It seems possible that AQP1 present in Gc and Tc cells may be implicated not only in the regulation of water homeostasis required for follicle development but also in cell proliferation and migration.

Fluxes of water through aquaporin 9 weaken membrane-cytoskeleton anchorage and promote formation of membrane protrusions.

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Thommie Karlsson

Full Text Available All modes of cell migration require rapid rearrangements of cell shape, allowing the cell to navigate within narrow spaces in an extracellular matrix. Thus, a highly flexible membrane and a dynamic cytoskeleton are crucial for rapid cell migration. Cytoskeleton dynamics and tension also play instrumental roles in the formation of different specialized cell membrane protrusions, viz. lamellipodia, filopodia, and membrane blebs. The flux of water through membrane-anchored water channels, known as aquaporins (AQPs has recently been implicated in the regulation of cell motility, and here we provide novel evidence for the role of AQP9 in the development of various forms of membrane protrusion. Using multiple imaging techniques and cellular models we show that: (i AQP9 induced and accumulated in filopodia, (ii AQP9-associated filopodial extensions preceded actin polymerization, which was in turn crucial for their stability and dynamics, and (iii minute, local reductions in osmolarity immediately initiated small dynamic bleb-like protrusions, the size of which correlated with the reduction in osmotic pressure. Based on this, we present a model for AQP9-induced membrane protrusion, where the interplay of water fluxes through AQP9 and actin dynamics regulate the cellular protrusive and motile activity of cells.

Distribution and quantitative changes in amounts of aquaporin 1, 5 and 9 in the pig uterus during the estrous cycle and early pregnancy

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Skowronski Mariusz T

2010-09-01

Full Text Available Abstract Background Aquaporins (AQPs are a family of membrane channel proteins that facilitate bulk water transport. To date, 11 isoforms of AQPs have been reported to be expressed in the female and male reproductive systems. The purpose of our study was to determine the localization and quantitative changes in the expression of AQP1, 5 and 9 within the pig uterus during different stages of the estrous cycle and early pregnancy. Methods Immunoperoxidase and semi-quantitative immunoblotting techniques were used to examine the distribution and changes in amounts of AQP1, AQP5 and AQP9 in uteral cells of pigs at the early (Days 2-4, middle (10-12, late (14-16 stage of the luteal phase and late (18-20 stage of the follicular phase of the estrous cycle as well as on Days 14-16 and 30-32 of gestation (the onset and the end of implantation process. Results The results demonstrated that AQP1, 5, and 9 were clearly detected in all studied stages of the estrous cycle and pregnancy. AQP1 was localized within uterine blood vessels. In cyclic gilts, endometrial and myometrial expression of AQP1 protein did not change significantly but increased during gestation. AQP5 was localized in smooth muscle cells and uterine epithelial cells. Endometrial expression of AQP5 protein did not change significantly between Days 2-4 and 10-12 of the estrous cycle but increased on Days 14-16 and 18-20 as well as during early pregnancy. Myometrial expression of AQP5 did not differ significantly during the estrous cycle but increased in the pregnancy. The anti-AQP9 antibody labeled uterine epithelial cells of uterus. Endometrial expression of AQP9 did not change significantly between Days 2-4 and 10-12 of the estrous cycle but increased on Days 14-16 and 18-20 as well as during early pregnancy. Conclusions The results suggest that a functional and distinctive collaboration exists among diverse AQPs in water handling during the different uterine phases in the estrous cycle and

Pretreatment with AQP4 and NKCC1 Inhibitors Concurrently Attenuated Spinal Cord Edema and Tissue Damage after Spinal Cord Injury in Rats.

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Yan, Xiaodong; Liu, Juanfang; Wang, Xiji; Li, Wenhao; Chen, Jingyuan; Sun, Honghui

2018-01-01

Spinal cord injury (SCI) affects more than 2.5 million people worldwide. Spinal cord edema plays critical roles in the pathological progression of SCI. This study aimed to delineate the roles of aquaporin 4 (AQP4) and Na + -K + -Cl - cotransporter 1 (NKCC1) in acute phase edema and tissue destruction after SCI and to explore whether inhibiting both AQP4 and NKCC1 could improve SCI-induced spinal edema and damage. Rat SCI model was established by modified Allen's method. Spinal cord water content, cerebrospinal fluid lactose dehydrogenase (LDH) activity, AQP4 and NKCC1 expression, and spinal cord pathology from 30 min to 7 days after SCI were monitored. Additionally, aforementioned parameters in rats treated with AQP4 and/or NKCC1 inhibitors were assessed 2 days after SCI. Spinal cord water content was significantly increased 1 h after SCI while AQP4 and NKCC1 expression and spinal fluid LDH activity elevated 6 h after SCI. Spinal cord edema and spinal cord destruction peaked around 24 h after SCI and maintained at high levels thereafter. Treating rats with AQP4 inhibitor TGN-020 and NKCC1 antagonist bumetanide significantly reduced spinal cord edema, tissue destruction, and AQP4 and NKCC1 expression after SCI in an additive manner. These results demonstrated the benefits of simultaneously inhibiting both AQP4 and NKCC1 after SCI.

Genetic ablation of AQP2 in the mouse connecting tubules results in a mild urinary concentrating defect

DEFF Research Database (Denmark)

Kortenoeven, Marleen; Pedersen, Nis Borbye; Miller, Lance

Body water balance is regulated in the kidney via the vasopressin (AVP) regulated water channel aquaporin-2 (AQP2) expressed in the connecting tubule (CNT) and the collecting duct (CD). Although crucial for the urinary concentrating mechanism, the relative role of AQP2 in the CNT and CD are not f...

Vasopressin increases S261 phosphorylation in AQP2-P262L, a mutant in recessive nephrogenic diabetes insipidus

NARCIS (Netherlands)

Trimpert, C.; van den Berg, D.T.; Fenton, R.A.; Klussmann, E.; Deen, P.M.T.

2012-01-01

Background Mutations in the aquaporin-2 (AQP2) gene cause nephrogenic diabetes insipidus (NDI), a renal disorder characterized by polyuria due to a lacking antidiuretic response to vasopressin. While most AQP2 mutants in recessive NDI are misfolded and retained in the endoplasmic reticulum,

The Expression of AQP1 IS Modified in Lung of Patients With Idiopathic Pulmonary Fibrosis: Addressing a Possible New Target

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Ana Galán-Cobo

2018-05-01

Full Text Available Activation of the epithelial-mesenchymal transition process (EMT by which alveolar cells in human lung tissue undergo differentiation giving rise to a mesenchymal phenotype (fibroblast/miofibroblasts has been well recognized as a key element in the origin of idiopathic pulmonary fibrosis (IPF. Here we analyzed expression of AQP1 in lung biopsies of patients diagnosed with IPF, and compared it to biopsies derived from patients with diverse lung pneumonies, such as hypersensitivity pneumonitis, sarcoidosis or normal lungs. Immunostaining for AQP1 showed a clear increment of AQP1 localized in the alveolar epithelium in biopsies from IPF patients alone. Moreover, to examine the possible participation of AQP1 in the pathophysiology of IPF, we evaluated its role in the pro-fibrotic transformation induced by transforming growth factor (TGF-β in vitro. Human alveolar epithelial cells (A549, and fibroblasts derived from an IPF patient (LL29, or fibroblasts from healthy normal lung tissue (MRC-5, were treated with TGF-β, and levels of expression of AQP1, as well as those of E-cadherin, vimentin, α-SMA and collagen were analyzed by RT-qPCR, western blot and immunohistochemistry. An increase of AQP1 mRNA and protein after TGF-β treatment (4–72h was observed either in A549 or IPF fibroblast-LL29 but not in MRC-5 fibroblasts. A gradual reduction of E-cadherin, and increased expression of vimentin, with no changes in α-SMA levels were observed in A549. Whereas in LL29 and MRC-5, TGF-β1 elicited a large production of collagen and α-SMA that was significantly greater in IPF fibroblast-LL29. Changes observed are consistent with activation of EMT by TGF-β, but whether modifications in AQP1 expression are responsible or independent events occurring at the same time is still unknown. Our results suggest that AQP1 plays a role in the pro-fibrotic TGF-β action and contributes to the etiology and pathophysiology of IPF. Understanding AQP1's role will help us

Effect of the cGMP pathway on AQP2 expression and translocation: potential implications for nephrogenic diabetes insipidus.

NARCIS (Netherlands)

Boone, M.; Kortenoeven, M.L.A.; Robben, J.H.; Deen, P.M.T.

2010-01-01

BACKGROUND: Arginine vasopressin (AVP) binding to the V2 receptor (V2R) in renal collecting duct principal cells induces a cAMP signalling cascade resulting in the activation of protein kinase A (PKA), translocation of aquaporin-2 (AQP2) to the apical membrane and an increase in AQP2 expression.

Aquaporin-4 deletion in mice reduces encephalopathy and brain edema in experimental acute liver failure.

Science.gov (United States)

Rama Rao, Kakulavarapu V; Verkman, A S; Curtis, Kevin M; Norenberg, Michael D

2014-03-01

Brain edema and associated astrocyte swelling leading to increased intracranial pressure are hallmarks of acute liver failure (ALF). Elevated blood and brain levels of ammonia have been implicated in the development of brain edema in ALF. Cultured astrocytes treated with ammonia have been shown to undergo cell swelling and such swelling was associated with an increase in the plasma membrane expression of aquaporin-4 (AQP4) protein. Further, silencing the AQP4 gene in cultured astrocytes was shown to prevent the ammonia-induced cell swelling. Here, we examined the evolution of brain edema in AQP4-null mice and their wild type counterparts (WT-mice) in different models of ALF induced by thioacetamide (TAA) or acetaminophen (APAP). Induction of ALF with TAA or APAP significantly increased brain water content in WT mice (by 1.6% ± 0.3 and 2.3 ± 0.4%, respectively). AQP4 protein was significantly increased in brain plasma membranes of WT mice with ALF induced by either TAA or APAP. In contrast to WT-mice, brain water content did not increase in AQP4-null mice. Additionally, AQP4-null mice treated with either TAA or APAP showed a remarkably lesser degree of neurological deficits as compared to WT mice; the latter displayed an inability to maintain proper gait, and demonstrated a markedly reduced exploratory behavior, with the mice remaining in one corner of the cage with its head tilted downwards. These results support a central role of AQP4 in the brain edema associated with ALF. Published by Elsevier Inc.

N-Acetylglutaminoyl-S-farnesyl-L-cysteine (SIG-1191): an anti-inflammatory molecule that increases the expression of the aquaglyceroporin, aquaporin-3, in human keratinocytes.

Science.gov (United States)

Fernández, José R; Webb, Corey; Rouzard, Karl; Voronkov, Michael; Huber, Kristen L; Stock, Jeffry B; Stock, Maxwell; Gordon, Joel S; Perez, Eduardo

2017-03-01

Isoprenylcysteine (IPC) small molecules were discovered as signal transduction modulating compounds ~25 years ago. More recently, IPC molecules have demonstrated antioxidant and anti-inflammatory properties in a variety of dermal cells as well as antimicrobial activity, representing a novel class of compounds to ameliorate skin conditions and disease. Here, we demonstrate a new IPC compound, N-acetylglutaminoyl-S-farnesyl-L-cysteine (SIG-1191), which inhibits UVB-induced inflammation blocking pro-inflammatory cytokine interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) production. To investigate further the previously reported hydrating potential of IPC compounds, SIG-1191 was tested for its ability to modulate aquaporin expression. Specifically, aquaporin 3 (AQP3) the most abundant aquaporin found in skin has been reported to play a key role in skin hydration, elasticity and barrier repair. Results show here for the first time that SIG-1191 increases AQP3 expression in both cultured normal human epidermal keratinocytes as well as when applied topically in a three-dimensional (3D) reconstructed human skin equivalent. Additionally, SIG-1191 dose dependently increased AQP3 protein levels, as determined by specific antibody staining, in the epidermis of the 3D skin equivalents. To begin to elucidate which signaling pathways SIG-1191 may be modulating to increase AQP3 levels, we used several pharmacological pathway inhibitors and determined that AQP3 expression is mediated by the Mitogen-activated protein kinase/Extracellular signal-regulated kinase kinase (MEK) pathway. Altogether, these data suggest SIG-1191 represents a new IPC derivative with anti-inflammatory activity that may also promote increased skin hydration based on its ability to increase AQP3 levels.

Pancreatic Aquaporin-7: A Novel Target for Anti-diabetic Drugs?

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Méndez-Giménez, Leire; Ezquerro, Silvia; da Silva, Inês V; Soveral, Graça; Frühbeck, Gema; Rodríguez, Amaia

2018-01-01

Aquaporins comprise a family of 13 members of water channels (AQP0-12) that facilitate a rapid transport of water across cell membranes. In some cases, these pores are also permeated by small solutes, particularly glycerol, urea or nitric oxide, among other solutes. Several aquaporins have been identified in the pancreas, an exocrine and endocrine organ that plays an essential role in the onset of insulin resistance and type 2 diabetes. The exocrine pancreas, which accounts for 90% of the total pancreas, secretes daily large volumes of a near-isotonic fluid containing digestive enzymes into the duodenum. AQP1, AQP5, and AQP8 contribute to fluid secretion especially from ductal cells, whereas AQP12 allows the proper maturation and exocytosis of secretory granules in acinar cells of the exocrine pancreas. The endocrine pancreas (10% of the total pancreatic cells) is composed by the islets of Langerhans, which are distributed in α, β, δ, ε, and pancreatic polypeptide (PP) cells that secrete glucagon, insulin, somatostatin, ghrelin and PP, respectively. AQP7, an aquaglyceroporin permeated by water and glycerol, is expressed in pancreatic β-cells and murine studies have confirmed its participation in insulin secretion, triacylglycerol synthesis and proliferation of these endocrine cells. In this regard, transgenic AQP7-knockout mice develop adult-onset obesity, hyperinsulinemia, increased intracellular triacylglycerol content and reduced β-cell mass in Langerhans islets. Moreover, we have recently reported that AQP7 upregulation in β-cells after bariatric surgery, an effective weight loss surgical procedure, contributes, in part, to the improvement of pancreatic steatosis and insulin secretion through the increase of intracytoplasmic glycerol in obese rats. Human studies remain scarce and controversial, with some rare cases of loss-of function mutations of the AQP7 gene being associated with the onset of type 2 diabetes. The present Review is focused on the role

Pancreatic aquaporin-7: a novel target for anti-diabetic drugs?

Science.gov (United States)

Méndez-Giménez, Leire; Ezquerro, Silvia; da Silva, Inês V.; Soveral, Graça; Frühbeck, Gema; Rodríguez, Amaia

2018-04-01

Aquaporins comprise a family of 13 members of water channels (AQP0-12) that facilitate a rapid transport of water across cell membranes. In some cases, these pores are also permeated by small solutes, particularly glycerol, urea or nitric oxide, among other solutes. Several aquaporins have been identified in the pancreas, an exocrine and endocrine organ that plays an essential role in the onset of insulin resistance and type 2 diabetes. The exocrine pancreas, which accounts for 90% of the total pancreas, secretes daily large volumes of a near-isotonic fluid containing digestive enzymes into the duodenum. AQP1, AQP5 and AQP8 contribute to fluid secretion especially from ductal cells, whereas AQP12 allows the proper maturation and exocytosis of secretory granules in acinar cells of the exocrine pancreas. The endocrine pancreas (10% of the total pancreatic cells) is composed by the islets of Langerhans, which are distributed in ,, ,  and pancreatic polypeptide (PP) cells that secrete glucagon, insulin, somatostatin, ghrelin and PP, respectively. AQP7, an aquaglyceroporin permeated by water and glycerol, is expressed in pancreatic -cells and murine studies have confirmed its participation in insulin secretion, triacylglycerol synthesis and proliferation of these endocrine cells. In this regard, transgenic AQP7-knockout mice develop adult-onset obesity, hyperinsulinemia, increased intracellular triacylglycerol content and reduced -cell mass in Langerhans islets. Moreover, we have recently reported that AQP7 upregulation in β-cells after bariatric surgery, an effective weight loss surgical procedure, contributes, in part, to the improvement of pancreatic steatosis and insulin secretion by increasing intracellular glycerol in obese rats. Human studies remain scarce and controversial, with some rare cases of loss-of function variants of the AQP7 gene being associated with the onset of type 2 diabetes. The present Review is focused on the role of

Pancreatic Aquaporin-7: A Novel Target for Anti-diabetic Drugs?

Directory of Open Access Journals (Sweden)

Leire Méndez-Giménez

2018-04-01

Full Text Available Aquaporins comprise a family of 13 members of water channels (AQP0-12 that facilitate a rapid transport of water across cell membranes. In some cases, these pores are also permeated by small solutes, particularly glycerol, urea or nitric oxide, among other solutes. Several aquaporins have been identified in the pancreas, an exocrine and endocrine organ that plays an essential role in the onset of insulin resistance and type 2 diabetes. The exocrine pancreas, which accounts for 90% of the total pancreas, secretes daily large volumes of a near-isotonic fluid containing digestive enzymes into the duodenum. AQP1, AQP5, and AQP8 contribute to fluid secretion especially from ductal cells, whereas AQP12 allows the proper maturation and exocytosis of secretory granules in acinar cells of the exocrine pancreas. The endocrine pancreas (10% of the total pancreatic cells is composed by the islets of Langerhans, which are distributed in α, β, δ, ε, and pancreatic polypeptide (PP cells that secrete glucagon, insulin, somatostatin, ghrelin and PP, respectively. AQP7, an aquaglyceroporin permeated by water and glycerol, is expressed in pancreatic β-cells and murine studies have confirmed its participation in insulin secretion, triacylglycerol synthesis and proliferation of these endocrine cells. In this regard, transgenic AQP7-knockout mice develop adult-onset obesity, hyperinsulinemia, increased intracellular triacylglycerol content and reduced β-cell mass in Langerhans islets. Moreover, we have recently reported that AQP7 upregulation in β-cells after bariatric surgery, an effective weight loss surgical procedure, contributes, in part, to the improvement of pancreatic steatosis and insulin secretion through the increase of intracytoplasmic glycerol in obese rats. Human studies remain scarce and controversial, with some rare cases of loss-of function mutations of the AQP7 gene being associated with the onset of type 2 diabetes. The present Review is

Hypoxia and hypoxia mimetics decrease aquaporin 5 (AQP5 expression through both hypoxia inducible factor-1α and proteasome-mediated pathways.

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Jitesh D Kawedia

Full Text Available The alveolar epithelium plays a central role in gas exchange and fluid transport, and is therefore critical for normal lung function. Since the bulk of water flux across this epithelium depends on the membrane water channel Aquaporin 5 (AQP5, we asked whether hypoxia had any effect on AQP5 expression. We show that hypoxia causes a significant (70% decrease in AQP5 expression in the lungs of mice exposed to hypoxia. Hypoxia and the hypoxia mimetic, cobalt, also caused similar decreases in AQP5 mRNA and protein expression in the mouse lung epithelial cell line MLE-12. The action of hypoxia and cobalt on AQP5 transcription was demonstrated by directly quantifying heternonuclear RNA by real-time PCR. Dominant negative mutants of Hypoxia Inducible Factor (HIF-1α and HIF-1α siRNA blocked the action of cobalt, showing that HIF-1α is a key component in this mechanism. The proteasome inhibitors, lactacystin or proteasome inhibitor-III completely abolished the effect of hypoxia and cobalt both at the protein and mRNA level indicating that the proteasome pathway is probably involved not only for the stability of HIF-1α protein, but for the stability of unidentified transcription factors that regulate AQP5 transcription. These studies reveal a potentially important physiological mechanism linking hypoxic stress and membrane water channels.

Hypoxia and Hypoxia Mimetics Decrease Aquaporin 5 (AQP5) Expression through Both Hypoxia Inducible Factor-1α and Proteasome-Mediated Pathways

Science.gov (United States)

Kawedia, Jitesh D.; Yang, Fan; Sartor, Maureen A.; Gozal, David; Czyzyk-Krzeska, Maria; Menon, Anil G.

2013-01-01

The alveolar epithelium plays a central role in gas exchange and fluid transport, and is therefore critical for normal lung function. Since the bulk of water flux across this epithelium depends on the membrane water channel Aquaporin 5 (AQP5), we asked whether hypoxia had any effect on AQP5 expression. We show that hypoxia causes a significant (70%) decrease in AQP5 expression in the lungs of mice exposed to hypoxia. Hypoxia and the hypoxia mimetic, cobalt, also caused similar decreases in AQP5 mRNA and protein expression in the mouse lung epithelial cell line MLE-12. The action of hypoxia and cobalt on AQP5 transcription was demonstrated by directly quantifying heternonuclear RNA by real-time PCR. Dominant negative mutants of Hypoxia Inducible Factor (HIF-1α) and HIF-1α siRNA blocked the action of cobalt, showing that HIF-1α is a key component in this mechanism. The proteasome inhibitors, lactacystin or proteasome inhibitor-III completely abolished the effect of hypoxia and cobalt both at the protein and mRNA level indicating that the proteasome pathway is probably involved not only for the stability of HIF-1α protein, but for the stability of unidentified transcription factors that regulate AQP5 transcription. These studies reveal a potentially important physiological mechanism linking hypoxic stress and membrane water channels. PMID:23469202

The gating mechanism of the human aquaporin 5 revealed by molecular dynamics simulations.

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Lorant Janosi

Full Text Available Aquaporins are protein channels located across the cell membrane with the role of conducting water or other small sugar alcohol molecules (aquaglyceroporins. The high-resolution X-ray structure of the human aquaporin 5 (HsAQP5 shows that HsAQP5, as all the other known aquaporins, exhibits tetrameric structure. By means of molecular dynamics simulations we analyzed the role of spontaneous fluctuations on the structural behavior of the human AQP5. We found that different conformations within the tetramer lead to a distribution of monomeric channel structures, which can be characterized as open or closed. The switch between the two states of a channel is a tap-like mechanism at the cytoplasmic end which regulates the water passage through the pore. The channel is closed by a translation of the His67 residue inside the pore. Moreover, water permeation rate calculations revealed that the selectivity filter, located at the other end of the channel, regulates the flow rate of water molecules when the channel is open, by locally modifying the orientation of His173. Furthermore, the calculated permeation rates of a fully open channel are in good agreement with the reported experimental value.

MAGNETIC NULL POINTS IN KINETIC SIMULATIONS OF SPACE PLASMAS

International Nuclear Information System (INIS)

Olshevsky, Vyacheslav; Innocenti, Maria Elena; Cazzola, Emanuele; Lapenta, Giovanni; Deca, Jan; Divin, Andrey; Peng, Ivy Bo; Markidis, Stefano

2016-01-01

We present a systematic attempt to study magnetic null points and the associated magnetic energy conversion in kinetic particle-in-cell simulations of various plasma configurations. We address three-dimensional simulations performed with the semi-implicit kinetic electromagnetic code iPic3D in different setups: variations of a Harris current sheet, dipolar and quadrupolar magnetospheres interacting with the solar wind, and a relaxing turbulent configuration with multiple null points. Spiral nulls are more likely created in space plasmas: in all our simulations except lunar magnetic anomaly (LMA) and quadrupolar mini-magnetosphere the number of spiral nulls prevails over the number of radial nulls by a factor of 3–9. We show that often magnetic nulls do not indicate the regions of intensive energy dissipation. Energy dissipation events caused by topological bifurcations at radial nulls are rather rare and short-lived. The so-called X-lines formed by the radial nulls in the Harris current sheet and LMA simulations are rather stable and do not exhibit any energy dissipation. Energy dissipation is more powerful in the vicinity of spiral nulls enclosed by magnetic flux ropes with strong currents at their axes (their cross sections resemble 2D magnetic islands). These null lines reminiscent of Z-pinches efficiently dissipate magnetic energy due to secondary instabilities such as the two-stream or kinking instability, accompanied by changes in magnetic topology. Current enhancements accompanied by spiral nulls may signal magnetic energy conversion sites in the observational data

Neuromyelitis optica spectrum disorders: comparison of clinical and magnetic resonance imaging characteristics of AQP4-IgG versus MOG-IgG seropositive cases in the Netherlands.

Science.gov (United States)

van Pelt, E D; Wong, Y Y M; Ketelslegers, I A; Hamann, D; Hintzen, R Q

2016-03-01

Neuromyelitis optica spectrum disorders (NMOSDs) are a group of rare inflammatory demyelinating disorders of the central nervous system. The identification of specific antibodies directed to aquaporin 4 (AQP4-IgG) led to the distinction from multiple sclerosis. However, up to 25% of the clinically diagnosed NMO patients are seronegative for AQP4-IgG. A subgroup of these patients might be identified by antibodies directed to myelin oligodendrocyte glycoprotein (MOG-IgG). Our objective was to investigate whether the clinical characteristics of these patients differ. Using a cell-based assay, samples of 61 AQP4-IgG seronegative patients and 41 AQP4-IgG seropositive patients with clinically NMOSD were analysed for the presence of MOG-IgG. Clinical characteristics of the AQP4-IgG, MOG-IgG seropositive and double seronegative NMOSD patients were compared. Twenty of the 61 AQP4-IgG seronegative patients tested MOG-IgG seropositive (33%). MOG-IgG seropositive patients were more frequently males in contrast to AQP4-IgG seropositive patients (55% vs. 15%, P < 0.01) and Caucasians (90% vs. 63%, P = 0.03). They more frequently presented with coincident optic neuritis and transverse myelitis (40% vs. 12%, P = 0.02) and had a monophasic disease course (70% vs. 29%, P < 0.01). AQP4-IgG seropositive patients were 2.4 times more likely to suffer from relapses compared with MOG-IgG seropositive patients (relative risk 2.4, 95% confidence interval 1.2-4.7). AQP4-IgG seropositive patients had higher Expanded Disability Status Scale levels at last follow-up (P < 0.01). Antibodies directed to MOG identify a subgroup of AQP4-IgG seronegative NMO patients with generally a favourable monophasic disease course. © 2015 EAN.

Lack of arginine vasopressin-induced phosphorylation of aquaporin-2 mutant AQP2-R254L explains dominant nephrogenic diabetes insipidus.

NARCIS (Netherlands)

Mattia, F.P. de; Savelkoul, P.J.M.; Kamsteeg, E.J.; Konings, I.B.M.; Sluijs, P. van der; Mallmann, R.; Oksche, A.; Deen, P.M.T.

2005-01-01

Water homeostasis in humans is regulated by vasopressin, which induces the translocation of homotetrameric aquaporin-2 (AQP2) water channels from intracellular vesicles to the apical membrane of renal principal cells. For this process, phosphorylation of AQP2 at S256 by cAMP-dependent protein kinase

Expression of aquaporin 9 in rat liver and efferent ducts of the male reproductive system after neonatal diethylstilbestrol exposure

DEFF Research Database (Denmark)

Wellejus, Anja; Jensen, Henrik E; Loft, Steffen

2008-01-01

Aquaporins (AQP) have important solute transport functions in many tissues including the epididymal efferent ducts (ED) and in the liver. We investigated the effect of neonatal exposure to diethylstilbestrol (DES) on AQP9 expressions in the ED and in the liver of rats. DES was administered from d...... to the epithelial cells of the ED. In conclusion, neonatal DES exposure appears to upregulate AQP9 channels in the ED in male rats, whereas a downregulation in the hepatic expression was observed, particularly in the periacinous area....

Repulsion between Lys258 and upstream arginines explains the missorting of the AQP2 mutant p.Glu258Lys in nephrogenic diabetes insipidus.

NARCIS (Netherlands)

Kamsteeg, E.J.; Stoffels, M.; Tamma, G.; Siemerink-Konings, I.B.M.; Deen, P.M.T.

2009-01-01

Regulation of body water homeostasis occurs by the vasopressin-dependent sorting of aquaporin-2 (AQP2) water channels to and from the apical membrane of renal principal cells. Mutations in AQP2 cause autosomal nephrogenic diabetes insipidus (NDI), a disease that renders the kidney unresponsive to

Melarsoprol sensitivity profile of Trypanosoma brucei gambiense isolates from cured and relapsed sleeping sickness patients from the Democratic Republic of the Congo.

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Patient Pyana Pati

2014-10-01

Full Text Available Sleeping sickness caused by Trypanosoma brucei (T.b. gambiense constitutes a serious health problem in sub-Sahara Africa. In some foci, alarmingly high relapse rates were observed in patients treated with melarsoprol, which used to be the first line treatment for patients in the neurological disease stage. Particularly problematic was the situation in Mbuji-Mayi, East Kasai Province in the Democratic Republic of the Congo with a 57% relapse rate compared to a 5% relapse rate in Masi-Manimba, Bandundu Province. The present study aimed at investigating the mechanisms underlying the high relapse rate in Mbuji-Mayi using an extended collection of recently isolated T.b. gambiense strains from Mbuji-Mayi and from Masi-Manimba.Forty five T.b. gambiense strains were used. Forty one were isolated from patients that were cured or relapsed after melarsoprol treatment in Mbuji-Mayi. In vivo drug sensitivity tests provide evidence of reduced melarsoprol sensitivity in these strains. This reduced melarsoprol sensitivity was not attributable to mutations in TbAT1. However, in all these strains, irrespective of the patient treatment outcome, the two aquaglyceroporin (AQP 2 and 3 genes are replaced by chimeric AQP2/3 genes that may be associated with resistance to pentamidine and melarsoprol. The 4 T.b. gambiense strains isolated in Masi-Manimba contain both wild-type AQP2 and a different chimeric AQP2/3. These findings suggest that the reduced in vivo melarsoprol sensitivity of the Mbuji-Mayi strains and the high relapse rates in that sleeping sickness focus are caused by mutations in the AQP2/AQP3 locus and not by mutations in TbAT1.We conclude that mutations in the TbAQP2/3 locus of the local T.b. gambiense strains may explain the high melarsoprol relapse rates in the Mbuji-Mayi focus but other factors must also be involved in the treatment outcome of individual patients.

[Impacts of the formula of Suoquanwan(SQW) on expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney of rat polyuria model of Yang-deficiency].

Science.gov (United States)

Cao, Hong-Ying; Wu, Qing-He; Huang, Ping; He, Jin-Yang

2009-06-01

To observe the impacts of the formula of Suoquanwan (SQW) on the expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney of rat polyuria model of Yang-deficiency. The model rats were induced by adenine (250 mg/kg) for 4 weeks, then treated respectively with SQW or dDAVP. The expression of AQP-2 mRNA and AVPR-V2 mRNA in kidney of Yang-deficiency model by realtime fluorescence quantitative PCR method were investigated. In model rats, the expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney decreased, dDAVP and SQW high dose could increased the expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney. The others had no influence on the expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney. SQW can increase the expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney of rat polyuria model of Yang-deficiency.

The aquaporin TcAQP1 of the desert truffle Terfezia claveryi is a membrane pore for water and CO(2) transport.

Science.gov (United States)

Navarro-Ródenas, Alfonso; Ruíz-Lozano, Juan Manuel; Kaldenhoff, Ralf; Morte, Asunción

2012-02-01

Terfezia claveryi is a hypogeous mycorrhizal fungus belonging to the so-called "desert truffles," with a good record as an edible fungus and of considerable economic importance. T. claveryi improves the tolerance to water stress of the host plant Helianthemum almeriense, for which, in field conditions, symbiosis with T. claveryi is valuable for its survival. We have characterized cDNAs from T. claveryi and identified a sequence related to the aquaporin gene family. The full-length sequence was obtained by rapid amplification of cDNA ends and was named TcAQP1. This aquaporin gene encoded a functional water-channel protein, as demonstrated by heterologous expression assays in Saccharomyces cerevisiae. The mycorrhizal fungal aquaporin increased both water and CO(2) conductivity in the heterologous expression system. The expression patterns of the TcAQP1 gene in mycelium, under different water potentials, and in mycorrhizal plants are discussed. The high levels of water conductivity of TcAQP1 could be related to the adaptation of this mycorrhizal fungus to semiarid areas. The CO(2) permeability of TcAQP1 could be involved in the regulation of T. claveryi growth during presymbiotic phases, making it a good candidate to be considered a novel molecular signaling channel in mycorrhizal fungi.

Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease.

Science.gov (United States)

Jurynczyk, Maciej; Probert, Fay; Yeo, Tianrong; Tackley, George; Claridge, Tim D W; Cavey, Ana; Woodhall, Mark R; Arora, Siddharth; Winkler, Torsten; Schiffer, Eric; Vincent, Angela; DeLuca, Gabriele; Sibson, Nicola R; Isabel Leite, M; Waters, Patrick; Anthony, Daniel C; Palace, Jacqueline

2017-12-06

The overlapping clinical features of relapsing remitting multiple sclerosis (RRMS), aquaporin-4 (AQP4)-antibody (Ab) neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-Ab disease mean that detection of disease specific serum antibodies is the gold standard in diagnostics. However, antibody levels are not prognostic and may become undetectable after treatment or during remission. Therefore, there is still a need to discover antibody-independent biomarkers. We sought to discover whether plasma metabolic profiling could provide biomarkers of these three diseases and explore if the metabolic differences are independent of antibody titre. Plasma samples from 108 patients (34 RRMS, 54 AQP4-Ab NMOSD, and 20 MOG-Ab disease) were analysed by nuclear magnetic resonance spectroscopy followed by lipoprotein profiling. Orthogonal partial-least squares discriminatory analysis (OPLS-DA) was used to identify significant differences in the plasma metabolite concentrations and produce models (mathematical algorithms) capable of identifying these diseases. In all instances, the models were highly discriminatory, with a distinct metabolite pattern identified for each disease. In addition, OPLS-DA identified AQP4-Ab NMOSD patient samples with low/undetectable antibody levels with an accuracy of 92%. The AQP4-Ab NMOSD metabolic profile was characterised by decreased levels of scyllo-inositol and small high density lipoprotein particles along with an increase in large low density lipoprotein particles relative to both RRMS and MOG-Ab disease. RRMS plasma exhibited increased histidine and glucose, along with decreased lactate, alanine, and large high density lipoproteins while MOG-Ab disease plasma was defined by increases in formate and leucine coupled with decreased myo-inositol. Despite overlap in clinical measures in these three diseases, the distinct plasma metabolic patterns support their distinct serological profiles and confirm that these

Effects of Cetuximab Combined with Celecoxib on Apoptosis and KDR and AQP1 
Expression in Lung Cancer

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Honggang XIA

2013-12-01

Full Text Available Background and objective Neoadjuvant chemotherapy is a new development in the treatment of lung cancer. In recent years, cetuximab and celecoxib have been commonly used in this procedure. This study aims to explore the effect of cetuximab combined with celecoxib on apoptosis and KDR and AQP1 expression in lung cancer A549 cells. Method The cells were cultured in RPMI-1640 and then divided into four groups: control group, 1 nmol/L cetuximab group, 25 µmol/L celecoxib group, and 1 nmol/L cetuximab+25 µmol/L celecoxib group. The treatment time was 48 h. The mRNA and protein expression levels of KDR and AQP1 were detected by RT-PCR and Western blot, respectively. The apoptosis, proliferation, and invasive ability of A549 cells before and after transfection were examined using flow cytometry, MTT, and transwell methods. Results Cetuximab and celecoxib inhibited the growth of A549 cells in a dose-dependent manner. Their combination produced a greater growth inhibition than when either was used alone (P<0.01. Cetuximab and celecoxib both induced the apoptosis of A549 cells, and their combination produced a higher apoptosis rate (P<0.01. Cetuximab in combination with celecoxib also induced G1 phase arrest and downregulated the expression of KDR and AQP1 in A549 cells (P<0.05. As a result, the invasion ability of the A549 cells was significantly decreased. Conclusion Cetuximab in combination with celecoxib can synergistically inhibit the growth of A549 cells and downregulate the expression of KDR and AQP1 in A549 cells. The combination of cetuximab and celecoxib is a potential strategy for lung cancer therapy.

Expression, Distribution and Role of Aquaporin Water Channels in Human and Animal Stomach and Intestines.

Science.gov (United States)

Zhu, Cui; Chen, Zhuang; Jiang, Zongyong

2016-08-29

Stomach and intestines are involved in the secretion of gastrointestinal fluids and the absorption of nutrients and fluids, which ensure normal gut functions. Aquaporin water channels (AQPs) represent a major transcellular route for water transport in the gastrointestinal tract. Until now, at least 11 AQPs (AQP1-11) have been found to be present in the stomach, small and large intestines. These AQPs are distributed in different cell types in the stomach and intestines, including gastric epithelial cells, gastric glands cells, absorptive epithelial cells (enterocytes), goblet cells and Paneth cells. AQP1 is abundantly distributed in the endothelial cells of the gastrointestinal tract. AQP3 and AQP4 are mainly distributed in the basolateral membrane of epithelial cells in the stomach and intestines. AQP7, AQP8, AQP10 and AQP11 are distributed in the apical of enterocytes in the small and large intestines. Although AQP-null mice displayed almost no phenotypes in gastrointestinal tracts, the alterations of the expression and localization of these AQPs have been shown to be associated with the pathology of gastrointestinal disorders, which suggests that AQPs play important roles serving as potential therapeutic targets. Therefore, this review provides an overview of the expression, localization and distribution of AQPs in the stomach, small and large intestine of human and animals. Furthermore, this review emphasizes the potential roles of AQPs in the physiology and pathophysiology of stomach and intestines.

Expression, Distribution and Role of Aquaporin Water Channels in Human and Animal Stomach and Intestines

Directory of Open Access Journals (Sweden)

Cui Zhu

2016-08-01

Full Text Available Stomach and intestines are involved in the secretion of gastrointestinal fluids and the absorption of nutrients and fluids, which ensure normal gut functions. Aquaporin water channels (AQPs represent a major transcellular route for water transport in the gastrointestinal tract. Until now, at least 11 AQPs (AQP1–11 have been found to be present in the stomach, small and large intestines. These AQPs are distributed in different cell types in the stomach and intestines, including gastric epithelial cells, gastric glands cells, absorptive epithelial cells (enterocytes, goblet cells and Paneth cells. AQP1 is abundantly distributed in the endothelial cells of the gastrointestinal tract. AQP3 and AQP4 are mainly distributed in the basolateral membrane of epithelial cells in the stomach and intestines. AQP7, AQP8, AQP10 and AQP11 are distributed in the apical of enterocytes in the small and large intestines. Although AQP-null mice displayed almost no phenotypes in gastrointestinal tracts, the alterations of the expression and localization of these AQPs have been shown to be associated with the pathology of gastrointestinal disorders, which suggests that AQPs play important roles serving as potential therapeutic targets. Therefore, this review provides an overview of the expression, localization and distribution of AQPs in the stomach, small and large intestine of human and animals. Furthermore, this review emphasizes the potential roles of AQPs in the physiology and pathophysiology of stomach and intestines.

Aquaporin 2 promotes cell migration and epithelial morphogenesis.

Science.gov (United States)

Chen, Ying; Rice, William; Gu, Zhizhan; Li, Jian; Huang, Jianmin; Brenner, Michael B; Van Hoek, Alfred; Xiong, Jianping; Gundersen, Gregg G; Norman, Jim C; Hsu, Victor W; Fenton, Robert A; Brown, Dennis; Lu, Hua A Jenny

2012-09-01

The aquaporin 2 (AQP2) water channel, expressed in kidney collecting ducts, contributes critically to water homeostasis in mammals. Animals lacking or having significantly reduced levels of AQP2, however, have not only urinary concentrating abnormalities but also renal tubular defects that lead to neonatal mortality from renal failure. Here, we show that AQP2 is not only a water channel but also an integrin-binding membrane protein that promotes cell migration and epithelial morphogenesis. AQP2 expression modulates the trafficking and internalization of integrin β1, facilitating its turnover at focal adhesions. In vitro, disturbing the interaction between AQP2 and integrin β1 by mutating the RGD motif led to reduced endocytosis, retention of integrin β1 at the cell surface, and defective cell migration and tubulogenesis. Similarly, in vivo, AQP2-null mice exhibited significant retention of integrin β1 at the basolateral membrane and had tubular abnormalities. In summary, these data suggest that the water channel AQP2 interacts with integrins to promote renal epithelial cell migration, contributing to the structural and functional integrity of the mammalian kidney.

On smoothness-asymmetric null infinities

International Nuclear Information System (INIS)

Valiente Kroon, Juan Antonio

2006-01-01

We discuss the existence of asymptotically Euclidean initial data sets for the vacuum Einstein field equations which would give rise (modulo an existence result for the evolution equations near spatial infinity) to developments with a past and a future null infinity of different smoothness. For simplicity, the analysis is restricted to the class of conformally flat, axially symmetric initial data sets. It is shown how the free parameters in the second fundamental form of the data can be used to satisfy certain obstructions to the smoothness of null infinity. The resulting initial data sets could be interpreted as those of some sort of (nonlinearly) distorted Schwarzschild black hole. Their developments would be that they admit a peeling future null infinity, but at the same time have a polyhomogeneous (non-peeling) past null infinity

Null solution of the Yang-Mills equations

International Nuclear Information System (INIS)

Tafel, J.

1986-05-01

We investigate the correspondence between null solutions of the Yang-Mills equations and shearfree geodesic null congruences. We give an example of a non-Abelian null solution with twisting rays. (orig.)

Null-strut calculus. II. Dynamics

International Nuclear Information System (INIS)

Kheyfets, A.; LaFave, N.J.; Miller, W.A.

1990-01-01

In this paper, we continue from the preceding paper to develop a fully functional Regge calculus geometrodynamic algorithm from the null-strut-calculus construction. The developments discussed include (a) the identification of the Regge calculus analogue of the constraint and evolution equations on the null-strut lattice, (b) a description of the Minkowski solid geometry for the simplicial blocks of the null-strut lattice, (c) a description of the evolution algorithm for the geometrodynamic scheme and an analysis of its consistency, and (d) a presentation of the dynamical degrees of freedom for a simplicial hypersurface and the description of an initial-value prescription. To demonstrate qualitatively this new approach to geometrodynamics, we present the most simple application of null-strut calculus that we know of---the Friedmann cosmology using the three-boundary of a 600-cell simplicial polytope to model the simplicial hypersurface

Visible Nulling Coronagraph Progress Report

Science.gov (United States)

Lyon, R. G.; Clampin, M.; Woodruff, R. A.; Vasudevan, G.; Thompson, P.; Petrone, P.; Madison, T.; Rizzo, M.; Melnick, G.; Tolls, V.

2010-10-01

We report on recent laboratory results with the NASA Goddard Space Flight Center Visible Nulling Coronagraph (VNC) testbed. We have achieved focal plane contrasts of 108 and approaching 109 at inner working angles of 2 λ/D and 4 λ/D, respectively. Results were obtained with a broadband source and 40 nm filter centered on 630 nm. A null control breadboard (NCB) was also developed to assess and quantify MEMS based deformable mirror technology (DM), and to develop and assess closed-loop null control algorithms. We have demonstrated closed-loop performance at 27 Hz.

Vacuum Nuller Testbed (VNT) Performance, Characterization and Null Control: Progress Report

Science.gov (United States)

Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Madison, Timothy; Bolcar, Matthew R.; Noecker, M. Charley; Kendrick, Stephen; Helmbrecht, Michael

2011-01-01

Herein we report on the development. sensing and control and our first results with the Vacuum Nuller Testbed to realize a Visible Nulling Coronagraph (VNC) for exoplanet coronagraphy. The VNC is one of the few approaches that works with filled. segmented and sparse or diluted-aperture telescope systems. It thus spans a range of potential future NASA telescopes and could be Hown as a separate instrument on such a future mission. NASA/Goddard Space Flight Center (GSFC) has a well-established effort to develop VNC technologies. and has developed an incremental sequence of VNC testbeds to advance this approach and the enabling technologies associated with it. We discuss the continued development of the vacuum Visible Nulling Coronagraph testbed (VNT). Tbe VNT is an ultra-stable vibration isolated testbed that operates under closed-loop control within a vacuum chamber. It will be used to achieve an incremental sequence of three visible-light nulling milestones with sequentially higher contrasts of 10(sup 8), 10(sup 9) and ideally 10(sup 10) at an inner working angle of 2*lambda/D. The VNT is based on a modified Mach-Zehnder nulling interferometer, with a "W" configuration to accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters. We discuss the initial laboratory results, the optical configuration, critical technologies and the null sensing and control approach.

Visible nulling coronagraph testbed results

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Lyon, Richard G.; Clampin, Mark; Woodruff, Robert A.; Vasudevan, Gopal; Thompson, Patrick; Petrone, Peter; Madison, Timothy; Rizzo, Maxime; Melnick, Gary; Tolls, Volker

2009-08-01

We report on our recent laboratory results with the NASA/Goddard Space Flight Center (GSFC) Visible Nulling Coronagraph (VNC) testbed. We have experimentally achieved focal plane contrasts of 1 x 108 and approaching 109 at inner working angles of 2 * wavelength/D and 4 * wavelength/D respectively where D is the aperture diameter. The result was obtained using a broadband source with a narrowband spectral filter of width 10 nm centered on 630 nm. To date this is the deepest nulling result with a visible nulling coronagraph yet obtained. Developed also is a Null Control Breadboard (NCB) to assess and quantify MEMS based segmented deformable mirror technology and develop and assess closed-loop null sensing and control algorithm performance from both the pupil and focal planes. We have demonstrated closed-loop control at 27 Hz in the laboratory environment. Efforts are underway to first bring the contrast to > 109 necessary for the direct detection and characterization of jovian (Jupiter-like) and then to > 1010 necessary for terrestrial (Earth-like) exosolar planets. Short term advancements are expected to both broaden the spectral passband from 10 nm to 100 nm and to increase both the long-term stability to > 2 hours and the extent of the null out to a ~ 10 * wavelength / D via the use of MEMS based segmented deformable mirror technology, a coherent fiber bundle, achromatic phase shifters, all in a vacuum chamber at the GSFC VNC facility. Additionally an extreme stability textbook sized compact VNC is under development.

Recent developments with the visible nulling coronagraph

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Hicks, Brian A.; Lyon, Richard G.; Bolcar, Matthew R.; Clampin, Mark; Petrone, Peter; Helmbrecht, Michael A.; Howard, Joseph M.; Miller, Ian J.

2016-08-01

A wide array of general astrophysics studies including detecting and characterizing habitable exoplanets could be enabled by a future large segmented telescope with sensitivity in the UV, optical, and infrared bands. When paired with a starshade or coronagraph, such an observatory could enable direct imaging and detailed spectroscopic observations of nearby Earth-like habitable zone planets. Over the past several years, a laboratory-based Visible Nulling Coronagraph (VNC) has evolved to reach requisite contrasts over a 1 nm bandwidth at narrow source angle separation using a segmented deformable mirror in one arm of a Mach-Zehnder layout. More recent efforts targeted broadband performance following the addition of two sets of half-wave Fresnel rhomb achromatic phase shifters (APS) with the goal of reaching 10-9 contrast, at a separation of 2λ/D, using a 40 nm (6%) bandwidth single mode fiber source. Here we present updates on the VNC broadband nulling effort, including approaches to addressing system contrast limitations.

Null structure groups in eleven dimensions

International Nuclear Information System (INIS)

Cariglia, Marco; Mac Conamhna, Oisin A. P.

2006-01-01

We classify all the structure groups which arise as subgroups of the isotropy group (Spin(7)xR 8 )xR, of a single null Killing spinor in 11 dimensions. We construct the spaces of spinors fixed by these groups. We determine the conditions under which structure subgroups of the maximal null structure group (Spin(7)xR 8 )xR may also be embedded in SU(5), and hence the conditions under which a supersymmetric spacetime admits only null, or both timelike and null, Killing spinors. We discuss how this purely algebraic material will facilitate the direct analysis of the Killing spinor equation of 11 dimensional supergravity, and the classification of supersymmetric spacetimes therein

Analysis of aquaporins from the euryhaline barnacle Balanus improvisus reveals differential expression in response to changes in salinity.

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Ulrika Lind

Full Text Available Barnacles are sessile macro-invertebrates, found along rocky shores in coastal areas worldwide. The euryhaline bay barnacle Balanus improvisus (Darwin, 1854 (= Amphibalanus improvisus can tolerate a wide range of salinities, but the molecular mechanisms underlying the osmoregulatory capacity of this truly brackish species are not well understood. Aquaporins are pore-forming integral membrane proteins that facilitate transport of water, small solutes and ions through cellular membranes, and that have been shown to be important for osmoregulation in many organisms. The knowledge of the function of aquaporins in crustaceans is, however, limited and nothing is known about them in barnacles. We here present the repertoire of aquaporins from a thecostracan crustacean, the barnacle B. improvisus, based on genome and transcriptome sequencing. Our analyses reveal that B. improvisus contains eight genes for aquaporins. Phylogenetic analysis showed that they represented members of the classical water aquaporins (Aqp1, Aqp2, the aquaglyceroporins (Glp1, Glp2, the unorthodox aquaporin (Aqp12 and the arthropod-specific big brain aquaporin (Bib. Interestingly, we also found two big brain-like proteins (BibL1 and BibL2 constituting a new group of aquaporins not yet described in arthropods. In addition, we found that the two water-specific aquaporins were expressed as C-terminal splice variants. Heterologous expression of some of the aquaporins followed by functional characterization showed that Aqp1 transported water and Glp2 water and glycerol, agreeing with the predictions of substrate specificity based on 3D modeling and phylogeny. To investigate a possible role for the B. improvisus aquaporins in osmoregulation, mRNA expression changes in adult barnacles were analysed after long-term acclimation to different salinities. The most pronounced expression difference was seen for AQP1 with a substantial (>100-fold decrease in the mantle tissue in low salinity (3

Visible Nulling Coronagraphy for Exo-Planetary Detection and Characterization

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Lyon, Richard G.; Clampin, Mark; Woodruff, Robert; Vasudevan, Gopal; Shao, Mike; Levine, Martin; Melnick, Gary; Tolls, Volker; Petrone, Peter; Dogoda, Peter; Duval, Julia; Ge, Jian

Visible Nulling Coronagraphy (VNC) is the proposed method of detecting and characterizing exo-solar Jovian planets (null depth 10-9) for the proposed NASA's Extrasolar Planetary Imaging Coronagraph (EPIC) Clampin & Lyon 2004 and is an approach under evaluation for NASA's Terrestrial Planet Finder (TPF) mission. The VNC approach uses a single unobscured filled-aperture telescope and splits, via a 50:50 beamsplitter, its re-imaged pupil into two paths within a Mach-Zender interferometer. An achromatic PI phase shift is imposed onto one beam path and the two paths are laterally sheared with respect to each other. The two beams are recombined at a second 50:50 beamsplitter. The net effect is that the on axis (stellar) light is transmitted out of the bright interferometer arm while the off-axis (planetary) light is transmitted out of the nulled interferometer arm. The bright output is used for fine pointing control and coarse wavefront control. The nulled output is relayed to the science camera for science imagery and fine wavefront control. The actual transmission pattern, projected on the sky, follows a θ^2 pattern for a single shear, θ^4 for a double shear, with the spacing of the successive maxima proportional to the inverse of the relative lateral shear. Combinations of shears and spacecraft rolls build up the spatial frequency content of the sky transmission pattern in the same manner as imaging interferometer builds up the spatial frequency content of the image.

Effects of total glucosides of peony on AQP-5 and its mRNA expression in submandibular glands of NOD mice with Sjogren's syndrome.

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Wu, G-L; Pu, X-H; Yu, G-Y; Li, T-Y

2015-01-01

The aim of this study was to observe the effects of total glucosides of peony (TGP) on pathological change, Aquaporin-5 (AQP-5) and its mRNA expression in submandibular glands of non-obese diabetic (NOD) mice with Sjogren's Syndrome, to investigate its regulation on secretion of salivary glands. 40 NOD mice were randomly divided into model group, TGP group, hydroxychloroquine group, combination group (n = 10). For TGP group, the mice were intragastrically administrated with 0.4 ml TGP dilution per day in accordance with 300 g/kg dose; for hydroxychloroquine group, the mice were intragastrically administrated with 0.4 ml hydroxychloroquine per day in accordance with 60 mg/kg dose; for the combination group, the mice were intragastrically administrated with 0.4 ml TGP dilution and 0.4 ml hydroxychloroquine. 8 weeks later, the mice were sacrificed, and submandibular glands were collected by anatomy. Pathological changes of submandibular gland were observed under a light microscope; AQP-5 protein in submandibular glands was detected by immunohistochemical staining; and AQP-5 mRNA expression in submandibular glands was detected by RT-PCR. The lymphocytic infiltration score of model mice was significantly higher than that of other groups. The pathological morphology and score of NOD mice were significantly improved after administration, and the combination group was superior to the hydroxychloroquine group and TGP group (p TGP group and the combination group were higher than the hydroxychloroquine group (p TGP may improve pathological damage of submandibular glands of NOD mouse with Sjogren's syndrome by upregulating AQP-5 and its mRNA expression in submandibular glands.

TRPV4 and AQP4 Channels Synergistically Regulate Cell Volume and Calcium Homeostasis in Retinal Müller Glia

DEFF Research Database (Denmark)

Jo, Andrew O; Ryskamp, Daniel A; Phuong, Tam T T

2015-01-01

Brain edema formation occurs after dysfunctional control of extracellular volume partly through impaired astrocytic ion and water transport. Here, we show that such processes might involve synergistic cooperation between the glial water channel aquaporin 4 (AQP4) and the transient receptor potent...

Effects of acupuncture at GV20 and ST36 on the expression of matrix metalloproteinase 2, aquaporin 4, and aquaporin 9 in rats subjected to cerebral ischemia/reperfusion injury.

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Hong Xu

Full Text Available BACKGROUND/PURPOSE: Ischemic stroke is characterized by high morbidity and mortality worldwide. Matrix metalloproteinase 2 (MMP2, aquaporin (AQP 4, and AQP9 are linked to permeabilization of the blood-brain barrier (BBB in cerebral ischemia/reperfusion injury (CIRI. BBB disruption, tissue inflammation, and MMP/AQP upregulation jointly provoke brain edema/swelling after CIRI, while acupuncture and electroacupuncture can alleviate CIRI symptoms. This study evaluated the hypothesis that acupuncture and electroacupuncture can similarly exert neuroprotective actions in a rat model of middle cerebral artery occlusion (MCAO by modulating MMP2/AQP4/APQ9 expression and inflammatory cell infiltration. METHODS: Eighty 8-week-old Sprague-Dawley rats were randomly divided into sham group S, MCAO model group M, acupuncture group A, electroacupuncture group EA, and edaravone group ED. The MCAO model was established by placement of a suture to block the middle carotid artery, and reperfusion was triggered by suture removal in all groups except group S. Acupuncture and electroacupuncture were administered at acupoints GV20 (governing vessel-20 and ST36 (stomach-36. Rats in groups A, EA, and ED received acupuncture, electroacupuncture, or edaravone, respectively, immediately after MCAO. Neurological function (assessed using the Modified Neurological Severity Score, infarct volume, MMP2/AQP4/AQP9 mRNA and protein expression, and inflammatory cell infiltration were all evaluated at 24 h post-reperfusion. RESULTS: Acupuncture and electroacupuncture significantly decreased infarct size and improved neurological function. Furthermore, target mRNA and protein levels and inflammatory cell infiltration were significantly reduced in groups A, EA, and ED vs. group M. However, MMP2/AQP levels and inflammatory cell infiltration were generally higher in groups A and EA than in group ED except MMP2 mRNA levels. CONCLUSIONS: Acupuncture and electroacupuncture at GV20 and ST36

On the Penrose inequality along null hypersurfaces

International Nuclear Information System (INIS)

Mars, Marc; Soria, Alberto

2016-01-01

The null Penrose inequality, i.e. the Penrose inequality in terms of the Bondi energy, is studied by introducing a functional on surfaces and studying its properties along a null hypersurface Ω extending to past null infinity. We prove a general Penrose-type inequality which involves the limit at infinity of the Hawking energy along a specific class of geodesic foliations called Geodesic Asymptotically Bondi (GAB), which are shown to always exist. Whenever this foliation approaches large spheres, this inequality becomes the null Penrose inequality and we recover the results of Ludvigsen–Vickers (1983 J. Phys. A: Math. Gen. 16 3349–53) and Bergqvist (1997 Class. Quantum Grav. 14 2577–83). By exploiting further properties of the functional along general geodesic foliations, we introduce an approach to the null Penrose inequality called the Renormalized Area Method and find a set of two conditions which imply the validity of the null Penrose inequality. One of the conditions involves a limit at infinity and the other a restriction on the spacetime curvature along the flow. We investigate their range of applicability in two particular but interesting cases, namely the shear-free and vacuum case, where the null Penrose inequality is known to hold from the results by Sauter (2008 PhD Thesis Zürich ETH ), and the case of null shells propagating in the Minkowski spacetime. Finally, a general inequality bounding the area of the quasi-local black hole in terms of an asymptotic quantity intrinsic of Ω is derived. (paper)

On the null origin of the ambitwistor string

Energy Technology Data Exchange (ETDEWEB)

Casali, Eduardo [Mathematical Institute, University of Oxford,Woodstock Road, Oxford, OX2 6GG (United Kingdom); Tourkine, Piotr [Department of Applied Mathematics and Theoretical Physics,Wilberforce Road, Cambridge, CB3 0WA (United Kingdom)

2016-11-07

In this paper we present the null string origin of the ambitwistor string. Classically, the null string is the tensionless limit of string theory, and so too is the ambitwistor string. Both have as constraint algebra the Galilean Conformal Algebra in two dimensions. But something interesting happens in the quantum theory since there is an ambiguity in quantizing the null string. We show that, given a particular choice of quantization scheme and a particular gauge, the null string coincides with the ambitwistor string both classically and quantum mechanically. We also show that the same holds for the spinning versions of the null string and ambitwistor string. With these results we clarify the relationship between the ambitwistor string, the null string, the usual string and the Hohm-Siegel-Zwiebach theory.

[Dilemma of null hypothesis in ecological hypothesis's experiment test.

Science.gov (United States)

Li, Ji

2016-06-01

Experimental test is one of the major test methods of ecological hypothesis, though there are many arguments due to null hypothesis. Quinn and Dunham (1983) analyzed the hypothesis deduction model from Platt (1964) and thus stated that there is no null hypothesis in ecology that can be strictly tested by experiments. Fisher's falsificationism and Neyman-Pearson (N-P)'s non-decisivity inhibit statistical null hypothesis from being strictly tested. Moreover, since the null hypothesis H 0 (α=1, β=0) and alternative hypothesis H 1 '(α'=1, β'=0) in ecological progresses are diffe-rent from classic physics, the ecological null hypothesis can neither be strictly tested experimentally. These dilemmas of null hypothesis could be relieved via the reduction of P value, careful selection of null hypothesis, non-centralization of non-null hypothesis, and two-tailed test. However, the statistical null hypothesis significance testing (NHST) should not to be equivalent to the causality logistical test in ecological hypothesis. Hence, the findings and conclusions about methodological studies and experimental tests based on NHST are not always logically reliable.

Comparison of spontaneous brain activity revealed by regional homogeneity in AQP4-IgG neuromyelitis optica-optic neuritis versus MOG-IgG optic neuritis patients: a resting-state functional MRI study

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Wang J

2017-10-01

Full Text Available Junqing Wang,1,* Yuan Tian,2,* Yi Shao,3,* Hui Feng,1 Limin Qin,1 Weiwei Xu,1 Hongjuan Liu,1 Quangang Xu,1 Shihui Wei,1 Lin Ma2 1Department of Ophthalmology, 2Department of Radiology, Chinese PLA General Hospital, Beijing, 3Department of Ophthalmology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Objective: Many previous studies have demonstrated that neuromyelitis optica (NMO patients have abnormalities of brain anatomy and function. However, differences in spontaneous brain activity between myelin oligodendrocyte glycoprotein (MOG-IgG ON and aquaporin 4(AQP4-neuromyelitis optica-optic neuritis (ON remain unknown. In the current study, we investigated the brain neural homogeneity in MOG-IgG ON versus AQP4-IgG NMO-ON subjects by regional homogeneity (ReHo method using magnetic resonance imaging (MRI. Patients and methods: A total of 32 NMO-ON and ON subjects (21 with AQP4-IgG+NMO-ON and 11 with MOG-IgG+ON and 34 healthy controls (HCs closely matched for age were recruited, and scans were performed for all subjects. A one-way analysis of variance (ANOVA was performed to determine the regions in which the ReHo was different across the three groups. NMO-ON and ON subjects were distinguished from HCs by a receiver operating characteristic (ROC curve. The relationship between the mean ReHo in many brain regions and clinical features in NMO subjects was calculated by Pearson correlation analysis. Results: Compared with HCs, MOG-IgG+ON subjects had significantly decreased ReHo values in the posterior lobe of the left cerebellum and increased ReHo values in the left inferior frontal gyrus, right prefrontal gyrus, and left precentral/postcentral gyrus. AQP4-IgG+NMO-ON subjects showed higher ReHo values in the left inferior frontal gyrus and right middle temporal/occipital gyrus. Compared with MOG-IgG+ON subjects, AQP4-IgG+NMO-ON subjects had lower Re

Decreased Expression of Na+/K+-ATPase, NHE3, NBC1, AQP1 and OAT in Gentamicin-induced Nephropathy

Science.gov (United States)

Bae, Woo Kyun; Lee, JongUn; Park, Jeong Woo; Bae, Eun Hui; Ma, Seong Kwon; Kim, Suhn Hee

2008-01-01

The present study was aimed to determine whether there is an altered regulation of tubular transporters in gentamicin-induced nephropathy. Sprague-Dawley male rats (200~250 g) were subcutaneously injected with gentamicin (100 mg/kg per day) for 7 days, and the expression of tubular transporters was determined by immunoblotting and immunohistochemistry. The mRNA and protein expression of OAT was also determined. Gentamicin-treated rats exhibited significantly decreased creatinine clearance along with increased plasma creatinine levels. Accordingly, the fractional excretion of sodium increased. Urine volume was increased, while urine osmolality and free water reabsorption were decreased. Immunoblotting and immunohistochemistry revealed decreased expression of Na+/K+-ATPase, NHE3, NBC1, and AQP1 in the kidney of gentamicin-treated rats. The expression of OAT1 and OAT3 was also decreased. Gentamicin-induced nephropathy may at least in part be causally related with a decreased expression of Na+/K+-ATPase, NHE3, NBC1, AQP1 and OAT. PMID:19967075

Function of the Membrane Water Channel Aquaporin-5 in the Salivary Gland

International Nuclear Information System (INIS)

Matsuzaki, Toshiyuki; Susa, Taketo; Shimizu, Kinue; Sawai, Nobuhiko; Suzuki, Takeshi; Aoki, Takeo; Yokoo, Satoshi; Takata, Kuniaki

2012-01-01

The process of saliva production in the salivary glands requires transepithelial water transfer from the interstitium to the acinar lumen. There are two transepithelial pathways: the transcellular and paracellular. In the transcellular pathway, the aquaporin water channels induce passive water diffusion across the membrane lipid bilayer. It is well known that aquaporin-5 (AQP5) is expressed in the salivary glands, in which it is mainly localized at the apical membrane of the acinar cells. This suggests the physiological importance of AQP5 in transcellular water transfer. Reduced saliva secretion under pilocarpine stimulation in AQP5-null mice compared with normal mice further indicates the importance of AQP5 in this process, at least in stimulated saliva secretion. Questions remain therefore regarding the role and importance of AQP5 in basal saliva secretion. It has been speculated that there would be some short-term regulation of AQP5 such as a trafficking mechanism to regulate saliva secretion. However, no histochemical evidence of AQP5-trafficking has been found, although some of biochemical analyses suggested that it may occur. There are no reports of human disease caused by AQP5 mutations, but some studies have revealed an abnormal subcellular distribution of AQP5 in patients or animals with xerostomia caused by Sjögren’s syndrome and X-irradiation. These findings suggest the possible pathophysiological importance of AQP5 in the salivary glands

Gravitational collapse of a cylindrical null shell in vacuum

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S. Khakshournia

2008-03-01

Full Text Available   Barrabès-Israel null shell formalism is used to study the gravitational collapse of a thin cylindrical null shell in vacuum. In general the lightlike matter shell whose history coincides with a null hypersurface is characterized by a surface energy density. In addition, a gravitational impulsive wave is present on this null hypersurface whose generators admit both the shear and expansion. In the case of imposing the cylindrical flatness the surface energy-momentum tensor of the matter shell on the null hypersurface vanishes and the null hyper- surface is just the history of the gravitational wave .

Bare Quantum Null Energy Condition.

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Fu, Zicao; Marolf, Donald

2018-02-16

The quantum null energy condition (QNEC) is a conjectured relation between a null version of quantum field theory energy and derivatives of quantum field theory von Neumann entropy. In some cases, divergences cancel between these two terms and the QNEC is intrinsically finite. We study the more general case here where they do not and argue that a QNEC can still hold for bare (unrenormalized) quantities. While the original QNEC applied only to locally stationary null congruences in backgrounds that solve semiclassical theories of quantum gravity, at least in the formal perturbation theory at a small Planck length, the quantum focusing conjecture can be viewed as the special case of our bare QNEC for which the metric is on shell.

Supersymmetric null-like holographic cosmologies

International Nuclear Information System (INIS)

Lin Fengli; Wen Wenyu

2006-01-01

We construct a new class of 1/4-BPS time dependent domain-wall solutions with null-like metric and dilaton in type II supergravities, which admit a null-like big bang singularity. Based on the domain-wall/QFT correspondence, these solutions are dual to 1/4-supersymmetric quantum field theories living on a boundary cosmological background with time dependent coupling constant and UV cutoff. In particular we evaluate the holographic c function for the 2-dimensional dual field theory living on the corresponding null-like cosmology. We find that this c function runs in accordance with the c-theorem as the boundary universe evolves, this means that the number of degrees of freedom is divergent at big bang and suggests the possible resolution of big bang singularity

Vasoactive Intestinal Peptide Protects Salivary Glands against Structural Injury and Secretory Dysfunction via IL-17A and AQP5 Regulation in a Model of Sjögren Syndrome.

Science.gov (United States)

Li, Chengyin; Zhu, Fenglin; Wu, Bin; Wang, Yue

2018-04-04

Sjögren syndrome (SS) is an autoimmune disease involving exocrine glands. Currently, drugs that can improve both abnormal immunity and exocrine gland function are needed. The study aimed to investigate the effect and mechanism of vasoactive intestinal peptide (VIP) on the immune response and exocrine gland function in SS. We investigated the effects of VIP on the immune response and secretory function of submandibular glands using NOD mice, and analyzed the expression of IL-17A and AQP5 (aquaporin 5). The submandibular gland cells from healthy 8-day-old Sprague-Dawley rats were used to observe the influence of VIP on AQP5 expression. Our study shows that treatment with VIP in an SS mouse model could not only reduce the immune injury to exocrine glands but also improve the secretory function of these glands. Furthermore, VIP was shown to improve the abnormal immune status by downregulating IL-17A expression in the exocrine glands. It also enhanced the secretory function of exocrine glands by upregulating AQP5 expression. Using a model of SS, we found that VIP could not only modulate the immune response but also affect exocrine gland function, and that these therapeutic effects were associated with IL-17A and AQP5 regulation. © 2018 S. Karger AG, Basel.

Effects of post-conditioning with sevoflurane on the expressions of intestinal AQP8 and I-FABP in pigs with hemorrhagic shock

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Yan-hong CHEN

2015-11-01

Full Text Available Objective　To observe the effects of sevoflurane post-conditioning on the expression of Aquaporin 8 (AQP8 and intestinal fatty acid binding protein (I-FABP, in order to investigate the protective role of sevoflurane post-conditioning on intestinal injury and its underlying mechanism. Methods　Eighteen bama miniature pigs were randomly divided into three groups (6 each using a random number table: control group (S group, hemorrhagic shock group (HS group, and sevoflurane post-coditioning group (Post/ Sev group. Experimental animals were fasted for 8 hours before surgery, and propofol 3mg/kg was given viathe ear vein. Endotracheal intubation was done when the animal fell asleep. Bloodletting from the femoral artery after anesthesia was done to reproduce hemorrhagic shock. In Post/Sev group, 2% sevoflurane was given by inhalation for 30min (post-conditioning after successful reproduction of the model. Blood samples were collected prior to anesthesia (T0 and 30min (T1, 1h (T2, 1.5h (T3, 2h (T4, 3h (T5, 4h (T6 after hemorrhagic shock. The quantity of blood I-FABP and intestinal AQP8 levels were determined with ELISA. Water content in the intestinal tissue was determined by wet and dry weight method. Histopathological changes in the intestinal tissue were observed with HE staining. Results　Compared with the control group, the serum I-FABP content, the expressions of intestinal AQP8, and water content in the intestinal tissue were significantly increased in HS group and Post/Sev (P<0.05 group. Compared with HS group, the above indices in Post/Sev group were significantly lower (P<0.05. These results were confirmed by pathological examination. Conclusion　Postconditioning with sevoflurane could improve, to some extent, pig's intestinal barrier function in hemorrhagic shock, and this effect is likely related with lowering of intestinal AQP8 and I-FABP expression and mucosal edema. DOI: 10.11855/j.issn.0577-7402.2015.11.11

Null infinity and extremal horizons in AdS-CFT

International Nuclear Information System (INIS)

Hickling, Andrew; Wiseman, Toby; Lucietti, James

2015-01-01

We consider AdS gravity duals to CFT on background spacetimes with a null infinity. Null infinity on the conformal boundary may extend to an extremal horizon in the bulk. For example it does so for Poincaré–AdS, although does not for planar Schwarzschild–AdS. If null infinity does extend into an extremal horizon in the bulk, we show that the bulk near-horizon geometry is determined by the geometry of the boundary null infinity. Hence the ‘infra-red’ geometry of the bulk is fixed by the large scale behaviour of the CFT spacetime. In addition the boundary stress tensor must have a particular decay at null infinity. As an application, we argue that for CFT on asymptotically flat backgrounds, any static bulk dual containing an extremal horizon extending from the boundary null infinity, must have the near-horizon geometry of Poincaré–AdS. We also discuss a class of boundary null infinity that cannot extend to a bulk extremal horizon, although we give evidence that they can extend to an analogous null surface in the bulk which possesses an associated scale-invariant ‘near-geometry’. (paper)

Null lifts and projective dynamics

Energy Technology Data Exchange (ETDEWEB)

Cariglia, Marco, E-mail: marco@iceb.ufop.br

2015-11-15

We describe natural Hamiltonian systems using projective geometry. The null lift procedure endows the tangent bundle with a projective structure where the null Hamiltonian is identified with a projective conic and induces a Weyl geometry. Projective transformations generate a set of known and new dualities between Hamiltonian systems, as for example the phenomenon of coupling-constant metamorphosis. We conclude outlining how this construction can be extended to the quantum case for Eisenhart–Duval lifts.

The Importance of Proving the Null

Science.gov (United States)

Gallistel, C. R.

2009-01-01

Null hypotheses are simple, precise, and theoretically important. Conventional statistical analysis cannot support them; Bayesian analysis can. The challenge in a Bayesian analysis is to formulate a suitably vague alternative, because the vaguer the alternative is (the more it spreads out the unit mass of prior probability), the more the null is…

Conformal symmetry inheritance in null fluid spacetimes

International Nuclear Information System (INIS)

Tupper, B O J; Keane, A J; Hall, G S; Coley, A A; Carot, J

2003-01-01

We define inheriting conformal Killing vectors for null fluid spacetimes and find the maximum dimension of the associated inheriting Lie algebra. We show that for non-conformally flat null fluid spacetimes, the maximum dimension of the inheriting algebra is seven and for conformally flat null fluid spacetimes the maximum dimension is eight. In addition, it is shown that there are two distinct classes of non-conformally flat generalized plane wave spacetimes which possess the maximum dimension, and one class in the conformally flat case

Myelin Formation during Development of the CNS Is Delayed in Matrix Metalloproteinase-9 and -12 Null Mice

DEFF Research Database (Denmark)

Larsen, Peter Hjørringgaard; DaSilva, Angelika G.; Conant, Kathrine

2006-01-01

was correlated with fewer mature oligodendrocytes, but similar precursor cell numbers, in MMP null animals compared with wild type. Because an important growth factor for oligodendrocyte maturation is insulin-like growth factor-1 (IGF-1), we addressed whether this was involved in the deficient myelination in MMP...

Changes in Air CO2 Concentration Differentially Alter Transcript Levels of NtAQP1 and NtPIP2;1 Aquaporin Genes in Tobacco Leaves

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Francesca Secchi

2016-04-01

Full Text Available The aquaporin specific control on water versus carbon pathways in leaves is pivotal in controlling gas exchange and leaf hydraulics. We investigated whether Nicotiana tabacum aquaporin 1 (NtAQP1 and Nicotiana tabacum plasma membrane intrinsic protein 2;1 (NtPIP2;1 gene expression varies in tobacco leaves subjected to treatments with different CO2 concentrations (ranging from 0 to 800 ppm, inducing changes in photosynthesis, stomatal regulation and water evaporation from the leaf. Changes in air CO2 concentration ([CO2] affected net photosynthesis (Pn and leaf substomatal [CO2] (Ci. Pn was slightly negative at 0 ppm air CO2; it was one-third that of ambient controls at 200 ppm, and not different from controls at 800 ppm. Leaves fed with 800 ppm [CO2] showed one-third reduced stomatal conductance (gs and transpiration (E, and their gs was in turn slightly lower than in 200 ppm– and in 0 ppm–treated leaves. The 800 ppm air [CO2] strongly impaired both NtAQP1 and NtPIP2;1 gene expression, whereas 0 ppm air [CO2], a concentration below any in vivo possible conditions and specifically chosen to maximize the gene expression alteration, increased only the NtAQP1 transcript level. We propose that NtAQP1 expression, an aquaporin devoted to CO2 transport, positively responds to CO2 scarcity in the air in the whole range 0–800 ppm. On the contrary, expression of NtPIP2;1, an aquaporin not devoted to CO2 transport, is related to water balance in the leaf, and changes in parallel with gs. These observations fit in a model where upregulation of leaf aquaporins is activated at low Ci, while downregulation occurs when high Ci saturates photosynthesis and causes stomatal closure.

ENERGY DISSIPATION IN MAGNETIC NULL POINTS AT KINETIC SCALES

International Nuclear Information System (INIS)

Olshevsky, Vyacheslav; Lapenta, Giovanni; Divin, Andrey; Eriksson, Elin; Markidis, Stefano

2015-01-01

We use kinetic particle-in-cell and MHD simulations supported by an observational data set to investigate magnetic reconnection in clusters of null points in space plasma. The magnetic configuration under investigation is driven by fast adiabatic flux rope compression that dissipates almost half of the initial magnetic field energy. In this phase powerful currents are excited producing secondary instabilities, and the system is brought into a state of “intermittent turbulence” within a few ion gyro-periods. Reconnection events are distributed all over the simulation domain and energy dissipation is rather volume-filling. Numerous spiral null points interconnected via their spines form null lines embedded into magnetic flux ropes; null point pairs demonstrate the signatures of torsional spine reconnection. However, energy dissipation mainly happens in the shear layers formed by adjacent flux ropes with oppositely directed currents. In these regions radial null pairs are spontaneously emerging and vanishing, associated with electron streams and small-scale current sheets. The number of spiral nulls in the simulation outweighs the number of radial nulls by a factor of 5–10, in accordance with Cluster observations in the Earth's magnetosheath. Twisted magnetic fields with embedded spiral null points might indicate the regions of major energy dissipation for future space missions such as the Magnetospheric Multiscale Mission

An omnibus test for the global null hypothesis.

Science.gov (United States)

Futschik, Andreas; Taus, Thomas; Zehetmayer, Sonja

2018-01-01

Global hypothesis tests are a useful tool in the context of clinical trials, genetic studies, or meta-analyses, when researchers are not interested in testing individual hypotheses, but in testing whether none of the hypotheses is false. There are several possibilities how to test the global null hypothesis when the individual null hypotheses are independent. If it is assumed that many of the individual null hypotheses are false, combination tests have been recommended to maximize power. If, however, it is assumed that only one or a few null hypotheses are false, global tests based on individual test statistics are more powerful (e.g. Bonferroni or Simes test). However, usually there is no a priori knowledge on the number of false individual null hypotheses. We therefore propose an omnibus test based on cumulative sums of the transformed p-values. We show that this test yields an impressive overall performance. The proposed method is implemented in an R-package called omnibus.

Vacuum Nuller Testbed Performance, Characterization and Null Control

Science.gov (United States)

Lyon, R. G.; Clampin, M.; Petrone, P.; Mallik, U.; Madison, T.; Bolcar, M.; Noecker, C.; Kendrick, S.; Helmbrecht, M. A.

2011-01-01

The Visible Nulling Coronagraph (VNC) can detect and characterize exoplanets with filled, segmented and sparse aperture telescopes, thereby spanning the choice of future internal coronagraph exoplanet missions. NASA/Goddard Space Flight Center (GSFC) has developed a Vacuum Nuller Testbed (VNT) to advance this approach, and assess and advance technologies needed to realize a VNC as a flight instrument. The VNT is an ultra-stable testbed operating at 15 Hz in vacuum. It consists of a MachZehnder nulling interferometer; modified with a "W" configuration to accommodate a hexpacked MEMS based deformable mirror (DM), coherent fiber bundle and achromatic phase shifters. The 2-output channels are imaged with a vacuum photon counting camera and conventional camera. Error-sensing and feedback to DM and delay line with control algorithms are implemented in a real-time architecture. The inherent advantage of the VNC is that it is its own interferometer and directly controls its errors by exploiting images from bright and dark channels simultaneously. Conservation of energy requires the sum total of the photon counts be conserved independent of the VNC state. Thus sensing and control bandwidth is limited by the target stars throughput, with the net effect that the higher bandwidth offloads stressing stability tolerances within the telescope. We report our recent progress with the VNT towards achieving an incremental sequence of contrast milestones of 10(exp 8) , 10(exp 9) and 10(exp 10) respectively at inner working angles approaching 2A/D. Discussed will be the optics, lab results, technologies, and null control. Shown will be evidence that the milestones have been achieved.

Ambitwistor strings at null infinity and (subleading) soft limits

International Nuclear Information System (INIS)

Geyer, Yvonne; Lipstein, Arthur E; Mason, Lionel

2015-01-01

The relationship between BMS symmetries at null infinity and Weinberg's soft theorems for gravitons and photons together with their subleading extensions are developed using ambitwistor string theory. Ambitwistor space is the phase space of complex null geodesics in complexified space-time. We show how it can be canonically identified with the cotangent bundle of complexified null infinity. BMS symmetries of null infinity lift to give a Hamiltonian action on ambitwistor space, both in general dimension and in its twistorial four-dimensional representation. General vertex operators arise from Hamiltonians generating diffeomorphisms of ambitwistor space that determine the scattering from past to future null infinity. When a momentum eigenstate goes soft, the diffeomorphism defined by its leading and its subleading part are extended BMS generators realized in the world sheet conformal field theory of the ambitwistor string. More generally, this gives an explicit perturbative correspondence between the scattering of null geodesics and that of the gravitational field via ambitwistor string theory. (paper)

Role of aquaporin and sodium channel in pleural water movement.

Science.gov (United States)

Jiang, Jinjun; Hu, Jie; Bai, Chunxue

2003-12-16

The role of the ENaC sodium channel and aquaporin-1 (AQP1) water channel on pleural fluid dynamics in mice was investigated. 0.25 ml of hypertonic or isosmolar fluid was infused into the pleural space in anesthetized wildtype and AQP1 null mice. Pleural fluid was sampled at specified times to quantify the osmolality and volume. The sodium channel activator terbutaline increased isosmolar fluid clearance by 90% while the sodium channel inhibitor amiloride decreased it by 15%, but had no effect on osmotically driven water transport. AQP1 deletion significantly decreased osmotic water transport in pleural space by twofold, but it had no effect on isosmolar fluid clearance. Pretreatment with dexamethasone increased pleural osmotic fluid entry by 25%, while intravenous injection of HgCl2 decreased osmotic pleural water movement by 43%. These results provided evidence for a role of a sodium channel in pleural fluid absorption; AQP1 plays a major role in osmotic liquid transport but it does not affect isosmolar fluid clearance.

Expression profiles of aquaporins in rat conjunctiva, cornea, lacrimal gland and Meibomian gland.

Science.gov (United States)

Yu, Dongfang; Thelin, William R; Randell, Scott H; Boucher, Richard C

2012-10-01

The aim of the study was to elucidate aquaporin (AQP) family member mRNA expression and protein expression/localization in the rat lacrimal functional unit. The mRNA expression of all rat AQPs (AQP0-9, 11-12) in palpebral, fornical, and bulbar conjunctiva, cornea, lacrimal gland, and Meibomian gland was measured by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and real time RT-PCR. Antibodies against AQP1, 3, 4, 5, 9, and 11 were used in Western blotting and immunohistochemistry to determine protein expression and distribution. Our study demonstrated characteristic AQP expression profiles in rat ocular tissues. AQP1, 3, 4, 5, 8, 9, 11, and 12 mRNA were detected in conjunctiva. AQP0, 1, 2, 3, 4, 5, 6, 11, and 12 mRNA were expressed in cornea. AQP0, 1, 2, 3, 4, 5, 7, 8, and 11 mRNA were detected in lacrimal gland. AQP1, 3, 4, 5, 7, 8, 9, 11, and 12 mRNA were identified in Meibomian gland. By Western blot, AQP1, 3, 5, and 11 were detected in conjunctiva; AQP1, 3, 5, and 11 were identified in cornea; AQP1, 3, 4, 5, and 11 were detected in lacrimal gland; and AQP1, 3, 4, 5, 9, and 11 were present in Meibomian gland. Immunohistochemistry localized AQPs to distinct sites in the various tissues. This study rigorously analyzed AQPs expression and localization in rat conjunctiva, cornea, lacrimal gland, and Meibomian gland tissues. Our findings provide a comprehensive platform for further investigation into the physiological or pathophysiological relevance of AQPs in ocular surface. Copyright © 2012 Elsevier Ltd. All rights reserved.

Null controllability of the viscous Camassa–Holm equation with ...

Indian Academy of Sciences (India)

In this paper, we study the null controllability of the viscous Camassa–. Holm equation on the one-dimensional torus. By using a moving distributed control, we obtain that the system is null controllable for a given data with certain regularity. Keywords. Viscous Camassa–Holm equation; null controllability; moving control;.

Null Subjects in European and Brazilian Portuguese

Directory of Open Access Journals (Sweden)

Pilar Barbosa

2005-12-01

Full Text Available The goals of this paper are twofold: a to provide a structural account of the effects of the informal ‘Avoid Pronoun Principle’, proposed in Chomsky (1981: 65 for the Null Subject Languages (NSLs, and b to compare, in European and Brazilian Portuguese (EP and BP, the distribution of the third person pronouns in its full and null forms, to check whether in written corpora BP incorporates signs of the ongoing loss of the null subject, largely attested in its contemporary spoken language. The strong theoretical claim is that in the Romance non-NSLs the pre-verbal subject is sitting in Spec of IP, while in the Romance NSLs it is Clitic Left-Dislocated (or is extracted by A-bar movement if it belongs to a restricted set of non-referential quantified expressions. The paper provides quantitative evidence that BP is losing the properties associated with the Null Subject Parameter. In its qualitative analysis, it shows that the contrasts between EP and BP are easily accounted for if the two derivations are assumed and if the null subjects in the two varieties are considered to be of a different nature: a pronoun in EP and a pronominal anaphor in BP.

Long-term aldosterone treatment induces decreased apical but increased basolateral expression of AQP2 in CCD of rat kidney.

NARCIS (Netherlands)

Seigneux, S. de; Nielsen, J.; Olesen, E.T.; Dimke, H.; Kwon, T.H.; Frokiaer, J.; Nielsen, S.

2007-01-01

The purpose of the present studies was to determine the effects of high-dose aldosterone and dDAVP treatment on renal aquaporin-2 (AQP2) regulation and urinary concentration. Rats were treated for 6 days with either vehicle (CON; n = 8), dDAVP (0.5 ng/h, dDAVP, n = 10), aldosterone (Aldo, 150

Inhibition of HMGB1 reduces rat spinal cord astrocytic swelling and AQP4 expression after oxygen-glucose deprivation and reoxygenation via TLR4 and NF-κB signaling in an IL-6-dependent manner.

Science.gov (United States)

Sun, Lin; Li, Man; Ma, Xun; Feng, Haoyu; Song, Junlai; Lv, Cong; He, Yajun

2017-11-25

Spinal cord astrocyte swelling is an important component to spinal cord edema and is associated with poor functional recovery as well as therapeutic resistance after spinal cord injury (SCI). High mobility group box-1 (HMGB1) is a mediator of inflammatory responses in the central nervous system and plays a critical role after SCI. Given this, we sought to identify both the role and underlying mechanisms of HMGB1 in cellular swelling and aquaporin 4 (AQP4) expression in cultured rat spinal cord astrocytes after oxygen-glucose deprivation/reoxygenation (OGD/R). The post-natal day 1-2 Sprague-Dawley rat spinal cord astrocytes were cultured in vitro, and the OGD/R model was induced. We first investigated the effects of OGD/R on spinal cord astrocytic swelling and HMGB1 and AQP4 expression, as well as HMGB1 release. We then studied the effects of HMGB1 inhibition on cellular swelling, HMGB1 and AQP4 expression, and HMGB1 release. The roles of both toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway and interleukin-6 (IL-6) in reducing cellular swelling resulting from HMGB1 inhibition in spinal cord astrocytes after OGD/R were studied. Intergroup data were compared using one-way analysis of variance (ANOVA) followed by Dunnett's test. The OGD/R increased spinal cord astrocytic swelling and HMGB1 and AQP4 expression, as well as HMGB1 release. Inhibition of HMGB1 using either HMGB1 shRNA or ethyl pyruvate resulted in reduced cellular volume, mitochondrial and endoplasmic reticulum swelling, and lysosome number and decreased upregulation of both HMGB1 and AQP4 in spinal cord astrocytes, as well as HMGB1 release. The HMGB1 effects on spinal cord astrocytic swelling and AQP4 upregulation after OGD/R were mediated-at least in part-via activation of TLR4, myeloid differentiation primary response gene 88 (MyD88), and NF-κB. These activation effects can be repressed by TLR4 inhibition using CLI-095 or C34, or by NF-κB inhibition using BAY 11

Null-strut calculus. I. Kinematics

International Nuclear Information System (INIS)

Kheyfets, A.; LaFave, N.J.; Miller, W.A.

1990-01-01

This paper describes the kinematics of null-strut calculus---a 3+1 Regge calculus approach to general relativity. We show how to model the geometry of spacetime with simplicial spacelike three-geometries (TET's) linked to ''earlier'' and ''later'' momentumlike lattice surfaces (TET * ) entirely by light rays or ''null struts.'' These three-layered lattice spacetime geometries are defined and analyzed using combinatorial formulas for the structure of polytopes. The following paper in this series describes how these three-layered spacetime lattices are used to model spacetimes in full conformity with Einstein's theory of gravity

Altered aquaporin expression in glaucoma eyes

DEFF Research Database (Denmark)

Tran, Thuy Linh; Bek, Toke; Cour, Morten la

2014-01-01

Aquaporins (AQP) are channels in the cell membrane that mainly facilitate a passive transport of water. In the eye, AQPs are expressed in the ciliary body and retina and may contribute to the pathogenesis of glaucoma and optic neuropathy. We investigated the expression of AQP1, AQP3, AQP4, AQP5......, AQP7 and AQP9 in human glaucoma eyes compared with normal eyes. Nine glaucoma eyes were examined. Of these, three eyes were diagnosed with primary open angle glaucoma; three eyes had neovascular glaucoma; and three eyes had chronic angle-closure glaucoma. Six eyes with normal intraocular pressure...... and without glaucoma were used as control. Immunohistochemistry was performed using antibodies against AQP1, AQP3, AQP4, AQP5, AQP7 and AQP9. For each specimen, optical densities of immunoprecipitates were measured using Photoshop and the staining intensities were calculated. Immunostaining showed labelling...

The Visible Nulling Coronagraph--Architecture Definition and Technology Development

Science.gov (United States)

Shao, Michael; Levine, B. Martin; Wallace, J. Kent; Liu, Duncan T.; Schmidtlin, Edouard; Serabyn, Eugene; Mennesson, Bertrand; Green, Joseph J.; Aguayo, Francisco; Fregoso, S. Felipe;

A Comparison of Plasma Performance Between Single-Null and Double-Null Configurations During Elming H-Mode

International Nuclear Information System (INIS)

Petrie, T.W.; Fenstermacher, M.E.; Allen, S.L.; Carlstrom, T.N.; Gohil, P.; Groebner, R.J.; Greenfield, C.M.; Hyatt, A.W.; Lasnier, C.J.; La Haye, R.J.; Leonard, A.W.; Mahdavi, M.A.; Osborne, T.H.; Porter, G.D.; Rhodes, T.L.; Thomas, D.M.; Watkins, J.G.; West, W.P.; Wolf, N.S.

1999-01-01

Tokamak plasma performance generally improves with increased shaping of the plasma cross section, such as higher elongation and higher triangularity. The stronger shaping, especially higher triangularity, leads to changes in the magnetic topology of the divertor. Because there are engineering and divertor physics issues associated with changes in the details of the divertor flux geometry, especially as the configuration transitions from a single-null (SN) divertor to a marginally balanced double-null (DN) divertor, we have undertaken a systematic evaluation of the plasma characteristics as the magnetic geometry is varied, particularly with respect to (1) energy confinement, (2) the response of the plasma to deuterium gas fueling, (3) the operational density range for the ELMing H-mode, and (4) heat flux sharing by the diverters. To quantify the degree of divertor imbalance (or equivalently, to what degree the shape is double-null or single-null), we define a parameter DRSEP. DRSEP is taken as the radial distance between the upper divertor separatrix and the lower divertor separatrix, as determined at the outboard midplane. For example, if DRSEP=O, the configuration is a magnetically balanced DN; if DRSEP = +1.0 cm, the divertor configuration is biased toward the upper divertor. Three examples are shown in Fig. 1. In the following discussions, VB drift is directed toward the lower divertor

Fine art of computing nulling interferometer maps

Science.gov (United States)

Hénault, F.

2008-07-01

Spaceborne nulling interferometers are often characterized by means of their nulling ratio, which is defined as the deepest possible extinction of one target star supposed to harbor an extra-solar system. Herein is shown that another parameter, which is the transmitting efficiency of nearby bright fringes, is also of prime importance. More generally, "nulling maps" formed by the whole destructive and constructive fringe pattern projected on-sky, are found to be very sensitive on the design of some subsystems constituting the interferometer. In particular, we consider Spatial Filtering (SF) and Achromatic Phase Shifter (APS) devices, both required achieving planet detection and characterization. Consequences of the SF choice (pinhole or single-mode optical fiber) and APS properties (with or without induced pupil-flip) are discussed, for both monochromatic and polychromatic cases. Examples of numerical simulations are provided for single Bracewell interferometer, Angel cross and X-array configurations, demonstrating noticeable differences in the aspect of resulting nulling maps. It is concluded that both FS and APS designs exhibit variable capacities for serendipitous planet discovery.

Latex allergy and filaggrin null mutations

DEFF Research Database (Denmark)

Carlsen, Berit C; Meldgaard, Michael; Hamann, Dathan

2011-01-01

to aeroallergens and it is possible that filaggrin null mutations also increase the risk of latex allergy. The aim of this paper was to examine the association between filaggrin null mutations and type I latex allergy. Methods Twenty latex allergic and 24 non-latex allergic dentists and dental assistants...... in the cases in this study may not have occurred through direct skin contact but through the respiratory organs via latex proteins that are absorbed in glove powder and aerosolized...

Qualification of a Null Lens Using Image-Based Phase Retrieval

Science.gov (United States)

Bolcar, Matthew R.; Aronstein, David L.; Hill, Peter C.; Smith, J. Scott; Zielinski, Thomas P.

2012-01-01

In measuring the figure error of an aspheric optic using a null lens, the wavefront contribution from the null lens must be independently and accurately characterized in order to isolate the optical performance of the aspheric optic alone. Various techniques can be used to characterize such a null lens, including interferometry, profilometry and image-based methods. Only image-based methods, such as phase retrieval, can measure the null-lens wavefront in situ - in single-pass, and at the same conjugates and in the same alignment state in which the null lens will ultimately be used - with no additional optical components. Due to the intended purpose of a Dull lens (e.g., to null a large aspheric wavefront with a near-equal-but-opposite spherical wavefront), characterizing a null-lens wavefront presents several challenges to image-based phase retrieval: Large wavefront slopes and high-dynamic-range data decrease the capture range of phase-retrieval algorithms, increase the requirements on the fidelity of the forward model of the optical system, and make it difficult to extract diagnostic information (e.g., the system F/#) from the image data. In this paper, we present a study of these effects on phase-retrieval algorithms in the context of a null lens used in component development for the Climate Absolute Radiance and Refractivity Observatory (CLARREO) mission. Approaches for mitigation are also discussed.

Evaluation of null-point detection methods on simulation data

Science.gov (United States)

Olshevsky, Vyacheslav; Fu, Huishan; Vaivads, Andris; Khotyaintsev, Yuri; Lapenta, Giovanni; Markidis, Stefano

2014-05-01

We model the measurements of artificial spacecraft that resemble the configuration of CLUSTER propagating in the particle-in-cell simulation of turbulent magnetic reconnection. The simulation domain contains multiple isolated X-type null-points, but the majority are O-type null-points. Simulations show that current pinches surrounded by twisted fields, analogous to laboratory pinches, are formed along the sequences of O-type nulls. In the simulation, the magnetic reconnection is mainly driven by the kinking of the pinches, at spatial scales of several ion inertial lentghs. We compute the locations of magnetic null-points and detect their type. When the satellites are separated by the fractions of ion inertial length, as it is for CLUSTER, they are able to locate both the isolated null-points, and the pinches. We apply the method to the real CLUSTER data and speculate how common are pinches in the magnetosphere, and whether they play a dominant role in the dissipation of magnetic energy.

Phase-space lagrangians for null spinning strings

International Nuclear Information System (INIS)

Barcelos-Neto, J.; Ruiz-Altaba, M.; Ramirez, C.

1990-01-01

The striking fact that normal-ordered null strings have the same critical dimension as their usual non-zero tension siblings can be understood from the observation that one must, in the tensionless case, keep all the conjugate momenta as independent dynamical variables, thus doubling the number of physical degrees of freedom. The fermionic momenta give rise to a second-class constraint which cannot be solved covariantly, but can be successfully incorporated into the first-class constraint algebra after gauge-fixing. The ghost contributions to the anomaly consist of two b-c (and also two β-γ systems in the supersymmetric case), of the single Virasoro sub(super)algebra for the closed null (spinning) string. In the appropriate gauge, the null (super)string is (super)chiral. (orig.)

Tensionless branes and the null string critical dimension

International Nuclear Information System (INIS)

Bozhilov, P.

1998-01-01

BRST quantization is carried out for a model of p-branes with second class constraints. After extension of the phase space the constraint algebra coincides with the one of null string when p=1. It is shown that in this case one can or cannot obtain critical dimension for the null string, depending on the choice of the operator ordering and corresponding vacuum states. When p>1, operator orderings leading to critical dimension in the p=1 case are not allowed. Admissible orderings give no restrictions on the dimension of the embedding space-time. Finally, a generalization to supersymmetric null branes is proposed

Technology Advancement of the Visible Nulling Coronagraph

Science.gov (United States)

Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Thompson, Patrick; Bolcar, Matt; Madison, Timothy; Woodruff, Robert; Noecker, Charley; Kendrick, Steve

2010-01-01

The critical high contrast imaging technology for the Extrasolar Planetary Imaging Coronagraph (EPIC) mission concept is the visible nulling coronagraph (VNC). EPIC would be capable of imaging jovian planets, dust/debris disks, and potentially super-Earths and contribute to answering how bright the debris disks are for candidate stars. The contrast requirement for EPIC is 10(exp 9) contrast at 125 milli-arseconds inner working angle. To advance the VNC technology NASA/Goddard Space Flight Center, in collaboration with Lockheed-Martin, previously developed a vacuum VNC testbed, and achieved narrowband and broadband suppression of the core of the Airy disk. Recently our group was awarded a NASA Technology Development for Exoplanet Missions to achieve two milestones: (i) 10(exp 8) contrast in narrowband light, and, (ii) 10(ecp 9) contrast in broader band light; one milestone per year, and both at 2 Lambda/D inner working angle. These will be achieved with our 2nd generation testbed known as the visible nulling testbed (VNT). It contains a MEMS based hex-packed segmented deformable mirror known as the multiple mirror array (MMA) and coherent fiber bundle, i.e. a spatial filter array (SFA). The MMA is in one interferometric arm and works to set the wavefront differences between the arms to zero. Each of the MMA segments is optically mapped to a single mode fiber of the SFA, and the SFA passively cleans the sub-aperture wavefront error leaving only piston, tip and tilt error to be controlled. The piston degree of freedom on each segment is used to correct the wavefront errors, while the tip/tilt is used to simultaneously correct the amplitude errors. Thus the VNT controls both amplitude and wavefront errors with a single MMA in closed-loop in a vacuum tank at approx.20 Hz. Herein we will discuss our ongoing progress with the VNT.

Resistivity at the field null of the FRC plasma

International Nuclear Information System (INIS)

Gerwin, R.A.

1989-01-01

In the absence of the major destructive instabilities, the configuration time is ultimately determined by particle and flux containment. If the profiles are ''gentle,'' then the anomalous flux-loss rate depends essentially on the anomalous resistivity at the field null. Conventional electrostatic quasi-linear models of anomalous cross-field resistive diffusivity are based upon the use of rvec E x rvec B drift velocities, and hence break down at the magnetic field null. In this paper, an electromagnetic treatment valid at the field null is developed, based upon the presence of flute-parity perturbations. An expression for anomalous resistivity at the field null in the quasi-linear approximation is derived by averaging in the ignorable direction over the random phases of the perturbations. The expression is valid for arbitrary (non-local) radial shapes of the perturbing modes (for example, the eigenfunctions need not be centered at the field null), and for an arbitrary ratio of real frequency to growth rate. The effective resistivity due to flute perturbations of the MHD type will be considered. 1 ref

Impaired Sperm Maturation in Rnase9 Knockout Mice1

Science.gov (United States)

Westmuckett, Andrew D.; Nguyen, Edward B.; Herlea-Pana, Oana M.; Alvau, Antonio; Salicioni, Ana M.; Moore, Kevin L.

2014-01-01

ABSTRACT Ribonuclease, RNase A family, 9 (RNASE9) is a ribonuclease A superfamily member that is expressed only in the epididymis. It is a small, secreted polypeptide, it lacks ribonuclease activity, and its function(s) is unknown. However, epididymis-specific expression suggests a role in sperm maturation. We generated Rnase9−/− mice to study RNASE9 function in vivo. We confirm that RNASE9 expression is restricted to the epididymis. Within the epididymis, RNASE9 is first detected in midcaput, persists through the distal caput and corpus, and wanes in the cauda. Rnase9−/− mice are born at the expected Mendelian ratio, have normal postnatal growth and development, and have no outwardly apparent phenotype. Spermatogenesis is normal, and Rnase9-null sperm are morphologically normal. Rnase9−/− males have normal fertility in unrestricted mating trials, and fertilization rates in in vitro fertilization assays are indistinguishable from wild-type mice. Visual observations coupled with analyses of sperm velocities shortly after swim out from the corpus shows that motility of Rnase9-null sperm is significantly impaired. However, no differences between wild-type and Rnase9-null sperm are detected by computer-assisted sperm analysis 10–90 min after sperm isolation from the corpus or cauda. Assessment of capacitation-dependent signaling pathways in Rnase9-null sperm showed that, while levels of tyrosine phosphorylation of sperm proteins were normal, there was decreased phosphorylation of protein kinase A substrates upon capacitation compared to wild-type mice. In conclusion, RNASE9 is dispensable for fertility, but the absence of RNASE9 during epididymal transit results in impaired sperm maturation. PMID:24719258

Extrasolar Planetary Imaging Coronagraph: Visible Nulling Coronagraph Testbed Results

Science.gov (United States)

Lyon, Richard G.

2008-01-01

The Extrasolar Planetary Imaging Coronagraph (EPIC) is a proposed NASA Discovery mission to image and characterize extrasolar giant planets in orbits with semi-major axes between 2 and 10 AU. EPIC will provide insights into the physical nature of a variety of planets in other solar systems complimenting radial velocity (RV) and astrometric planet searches. It will detect and characterize the atmospheres of planets identified by radial velocity surveys, determine orbital inclinations and masses, characterize the atmospheres around A and F stars, observed the inner spatial structure and colors of inner Spitzer selected debris disks. EPIC would be launched to heliocentric Earth trailing drift-away orbit, with a 3-year mission lifetime ( 5 year goal) and will revisit planets at least three times at intervals of 9 months. The starlight suppression approach consists of a visible nulling coronagraph (VNC) that enables high order starlight suppression in broadband light. To demonstrate the VNC approach and advance it's technology readiness the NASA Goddard Space Flight Center and Lockheed-Martin have developed a laboratory VNC and have demonstrated white light nulling. We will discuss our ongoing VNC work and show the latest results from the VNC testbed,

Matter sources for a null big bang

International Nuclear Information System (INIS)

Bronnikov, K A; Zaslavskii, O B

2008-01-01

We consider the properties of stress-energy tensors compatible with a null big bang, i.e., cosmological evolution starting from a Killing horizon rather than a singularity. For Kantowski-Sachs cosmologies, it is shown that if matter satisfies the null energy condition, then (i) regular cosmological evolution can only start from a Killing horizon, (ii) matter is absent at the horizon and (iii) matter can only appear in the cosmological region due to interaction with vacuum. The latter is understood phenomenologically as a fluid whose stress tensor is insensitive to boosts in a particular direction. We also argue that matter is absent in a static region beyond the horizon. All this generalizes the observations recently obtained for a mixture of dust and a vacuum fluid. If, however, we admit the existence of phantom matter, its certain special kinds (with the parameter w ≤ -3) are consistent with a null big bang without interaction with vacuum (or without vacuum fluid at all). Then in the static region there is matter with w ≥ -1/3. Alternatively, the evolution can begin from a horizon in an infinitely remote past, leading to a scenario combining the features of a null big bang and an emergent universe

Tolerance analysis of null lenses using an end-use system performance criterion

Science.gov (United States)

Rodgers, J. Michael

2000-07-01

An effective method of assigning tolerances to a null lens is to determine the effects of null-lens fabrication and alignment errors on the end-use system itself, not simply the null lens. This paper describes a method to assign null- lens tolerances based on their effect on any performance parameter of the end-use system.

The underlying physiological basis of the desert rodent Meriones shawi's survival to prolonged water deprivation: Central vasopressin regulation on peripheral kidney water channels AQPs-2.

Science.gov (United States)

Elgot, A; El Hiba, O; Belkouch, M; Gamrani, H

2018-02-01

Meriones shawi (M. shawi) is a particular semi-desert rodent known by its resistance to long periods of thirst. The aim of the present investigation is to clarify the underlying mechanisms allowing M. shawi to resist to hard conditions of dehydration. For this reason we used two different approaches: i) a morphometric study, which consists in measuring the effect of dehydration on body and kidneys weights as well as the report kidney weight/body weight, ii) By immunohistochemistry, we proceed to study the effect of dehydration on the immunoreactivity of central vasopressin (AVP) and the kidney aquaporin-2 (AQP-2) which is a channel protein that allows water to permeate across cell membranes. Our results showed both a body mass decrease accompanied by a remarkable kidneys hypertrophy. The immunohistochemical study showed a significant increase of AQP-2 immunoreactivity in the medullar part of Meriones kidneys allowing probably to Meriones a great ability to water retention. Consistently, we demonstrate that the increased AQP-2 expression occurred together with an increase in vasopressin (AVP) expression in both hypothalamic supraoptic (SON) and paraventricular nucleus (PVN), which are a major hub in the osmotic control circuitry. These various changes seen either in body weight and kidneys or at the cellular level might be the basis of peripheral control of body water homeostasis, providing to M. shawia strong resistance against chronic dehydration. Copyright © 2017 Elsevier GmbH. All rights reserved.

Premeiotic germ cell defect in seminiferous tubules of Atm-null testis

International Nuclear Information System (INIS)

Takubo, Keiyo; Hirao, Atsushi; Ohmura, Masako; Azuma, Masaki; Arai, Fumio; Nagamatsu, Go; Suda, Toshio

2006-01-01

Lifelong spermatogenesis is maintained by coordinated sequential processes including self-renewal of stem cells, proliferation of spermatogonial cells, meiotic division, and spermiogenesis. It has been shown that ataxia telangiectasia-mutated (ATM) is required for meiotic division of the seminiferous tubules. Here, we show that, in addition to its role in meiosis, ATM has a pivotal role in premeiotic germ cell maintenance. ATM is activated in premeiotic spermatogonial cells and the Atm-null testis shows progressive degeneration. In Atm-null testicular cells, differing from bone marrow cells of Atm-null mice, reactive oxygen species-mediated p16 Ink4a activation does not occur in Atm-null premeiotic germ cells, which suggests the involvement of different signaling pathways from bone marrow defects. Although Atm-null bone marrow undergoes p16 Ink4a -mediated cellular senescence program, Atm-null premeiotic germ cells exhibited cell cycle arrest and apoptotic elimination of premeiotic germ cells, which is different from p16 Ink4a -mediated senescence

Variational principle for gravity with null and non-null boundaries: a unified boundary counter-term

Energy Technology Data Exchange (ETDEWEB)

Parattu, Krishnamohan; Chakraborty, Sumanta; Padmanabhan, T. [IUCAA, Post Bag 4, Pune (India)

2016-03-15

It is common knowledge that the Einstein-Hilbert action does not furnish a well-posed variational principle. The usual solution to this problem is to add an extra boundary term to the action, called a counter-term, so that the variational principle becomes well-posed. When the boundary is spacelike or timelike, the Gibbons-Hawking-York counter-term is the most widely used. For null boundaries, we had proposed a counter-term in a previous paper. In this paper, we extend the previous analysis and propose a counter-term that can be used to eliminate variations of the ''off-the-surface'' derivatives of the metric on any boundary, regardless of its spacelike, timelike or null nature. (orig.)

Visible nulling coronagraphy testbed development for exoplanet detection

Science.gov (United States)

Lyon, Richard G.; Clampin, Mark; Woodruff, Robert A.; Vasudevan, Gopal; Thompson, Patrick; Chen, Andrew; Petrone, Peter; Booth, Andrew; Madison, Timothy; Bolcar, Matthew; Noecker, M. Charley; Kendrick, Stephen; Melnick, Gary; Tolls, Volker

2010-07-01

Three of the recently completed NASA Astrophysics Strategic Mission Concept (ASMC) studies addressed the feasibility of using a Visible Nulling Coronagraph (VNC) as the prime instrument for exoplanet science. The VNC approach is one of the few approaches that works with filled, segmented and sparse or diluted aperture telescope systems and thus spans the space of potential ASMC exoplanet missions. NASA/Goddard Space Flight Center (GSFC) has a well-established effort to develop VNC technologies and has developed an incremental sequence of VNC testbeds to advance the this approach and the technologies associated with it. Herein we report on the continued development of the vacuum Visible Nulling Coronagraph testbed (VNT). The VNT is an ultra-stable vibration isolated testbed that operates under high bandwidth closed-loop control within a vacuum chamber. It will be used to achieve an incremental sequence of three visible light nulling milestones of sequentially higher contrasts of 108, 109 and 1010 at an inner working angle of 2*λ/D and ultimately culminate in spectrally broadband (>20%) high contrast imaging. Each of the milestones, one per year, is traceable to one or more of the ASMC studies. The VNT uses a modified Mach-Zehnder nulling interferometer, modified with a modified "W" configuration to accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters. Discussed will be the optical configuration laboratory results, critical technologies and the null sensing and control approach.

Meterwavelength Single-pulse Polarimetric Emission Survey. III. The Phenomenon of Nulling in Pulsars

Energy Technology Data Exchange (ETDEWEB)

Basu, Rahul; Mitra, Dipanjan; Melikidze, George I., E-mail: rahulbasu.astro@gmail.com [Janusz Gil Institute of Astronomy, University of Zielona Góra, ul. Szafrana 2, 65–516 Zielona Góra (Poland)

2017-09-10

A detailed analysis of nulling was conducted for the pulsars studied in the Meterwavelength Single-pulse Polarimetric Emission Survey. We characterized nulling in 36 pulsars including 17 pulsars where the phenomenon was reported for the first time. The most dominant nulls lasted for a short duration, less than five periods. Longer duration nulls extending to hundreds of periods were also seen in some cases. A careful analysis showed the presence of periodicities in the transition from the null to the burst states in 11 pulsars. In our earlier work, fluctuation spectrum analysis showed multiple periodicities in 6 of these 11 pulsars. We demonstrate that the longer periodicity in each case was associated with nulling. The shorter periodicities usually originate from subpulse drifting. The nulling periodicities were more aligned with the periodic amplitude modulation, indicating a possible common origin for both. The most prevalent nulls last for a single period and can be potentially explained using random variations affecting the plasma processes in the pulsar magnetosphere. On the other hand, longer-duration nulls require changes in the pair-production processes, which need an external triggering mechanism for the changes. The presence of periodic nulling puts an added constraint on the triggering mechanism, which also needs to be periodic.

Emission and null coordinates: geometrical properties and physical construction

International Nuclear Information System (INIS)

Coll, Bartolome; Ferrando, Joan J; Morales-Lladosa, Juan A

2011-01-01

A Relativistic Positioning System is defined by four clocks (emitters) broadcasting their proper time. Then, every event reached by the signals is naturally labeled by these four times which are the emission coordinates of this event. The coordinate hypersurfaces of the emission coordinates are the future light cones based on the emitter trajectories. For this reason the emission coordinates have been also named null coordinates or light coordinates. Nevertheless, other coordinate systems used in different relativistic contexts have the own right to be named null or light coordinates. Here we analyze when one can say that a coordinate is a null coordinate and when one can say that a coordinate system is null. Moreover, we examine the physical construction and the geometrical properties of several n ull coordinate systems : the emission and the reception coordinates, the radar coordinates, and the Bondi-Sachs coordinates, among others.

Shocks and currents in stratified atmospheres with a magnetic null point

Science.gov (United States)

Tarr, Lucas A.; Linton, Mark

2017-08-01

We use the resistive MHD code LARE (Arber et al 2001) to inject a compressive MHD wavepacket into a stratified atmosphere that has a single magnetic null point, as recently described in Tarr et al 2017. The 2.5D simulation represents a slice through a small ephemeral region or area of plage. The strong gradients in field strength and connectivity related to the presence of the null produce substantially different dynamics compared to the more slowly varying fields typically used in simple sunspot models. The wave-null interaction produces a fast mode shock that collapses the null into a current sheet and generates a set of outward propagating (from the null) slow mode shocks confined to field lines near each separatrix. A combination of oscillatory reconnection and shock dissipation ultimately raise the plasma's internal energy at the null and along each separatrix by 25-50% above the background. The resulting pressure gradients must be balanced by Lorentz forces, so that the final state has contact discontinuities along each separatrix and a persistent current at the null. The simulation demonstrates that fast and slow mode waves localize currents to the topologically important locations of the field, just as their Alfvenic counterparts do, and also illustrates the necessity of treating waves and reconnection as coupled phenomena.

Magnetoacoustic Waves in a Stratified Atmosphere with a Magnetic Null Point

Energy Technology Data Exchange (ETDEWEB)

Tarr, Lucas A.; Linton, Mark; Leake, James, E-mail: lucas.tarr.ctr@nrl.navy.mil [U.S. Naval Research Laboratory, 4555 Overlook Ave. SW, Washington, DC 20375 (United States)

2017-03-01

We perform nonlinear MHD simulations to study the propagation of magnetoacoustic waves from the photosphere to the low corona. We focus on a 2D system with a gravitationally stratified atmosphere and three photospheric concentrations of magnetic flux that produce a magnetic null point with a magnetic dome topology. We find that a single wavepacket introduced at the lower boundary splits into multiple secondary wavepackets. A portion of the packet refracts toward the null owing to the varying Alfvén speed. Waves incident on the equipartition contour surrounding the null, where the sound and Alfvén speeds coincide, partially transmit, reflect, and mode-convert between branches of the local dispersion relation. Approximately 15.5% of the wavepacket’s initial energy ( E {sub input}) converges on the null, mostly as a fast magnetoacoustic wave. Conversion is very efficient: 70% of the energy incident on the null is converted to slow modes propagating away from the null, 7% leaves as a fast wave, and the remaining 23% (0.036 E {sub input}) is locally dissipated. The acoustic energy leaving the null is strongly concentrated along field lines near each of the null’s four separatrices. The portion of the wavepacket that refracts toward the null, and the amount of current accumulation, depends on the vertical and horizontal wavenumbers and the centroid position of the wavepacket as it crosses the photosphere. Regions that refract toward or away from the null do not simply coincide with regions of open versus closed magnetic field or regions of particular field orientation. We also model wavepacket propagation using a WKB method and find that it agrees qualitatively, though not quantitatively, with the results of the numerical simulation.

A new dynamic null model for phylogenetic community structure

NARCIS (Netherlands)

Pigot, Alex L; Etienne, Rampal S

Phylogenies are increasingly applied to identify the mechanisms structuring ecological communities but progress has been hindered by a reliance on statistical null models that ignore the historical process of community assembly. Here, we address this, and develop a dynamic null model of assembly by

Continuous development of current sheets near and away from magnetic nulls

International Nuclear Information System (INIS)

Kumar, Sanjay; Bhattacharyya, R.

2016-01-01

The presented computations compare the strength of current sheets which develop near and away from the magnetic nulls. To ensure the spontaneous generation of current sheets, the computations are performed congruently with Parker's magnetostatic theorem. The simulations evince current sheets near two dimensional and three dimensional magnetic nulls as well as away from them. An important finding of this work is in the demonstration of comparative scaling of peak current density with numerical resolution, for these different types of current sheets. The results document current sheets near two dimensional magnetic nulls to have larger strength while exhibiting a stronger scaling than the current sheets close to three dimensional magnetic nulls or away from any magnetic null. The comparative scaling points to a scenario where the magnetic topology near a developing current sheet is important for energetics of the subsequent reconnection.

Null-plane quantization of fermions

International Nuclear Information System (INIS)

Mustaki, D.

1990-01-01

Massive Dirac fermions are canonically quantized on the null plane using the Dirac-Bergmann algorithm. The procedure is carried out in the framework of quantum electrodynamics as an illustration of a rigorous treatment of interacting fermion fields

Approaches for achieving broadband achromatic phase shifts for visible nulling coronagraphy

Science.gov (United States)

Bolcar, Matthew R.; Lyon, Richard G.

2012-07-01

Visible nulling coronagraphy is one of the few approaches to the direct detection and characterization of Jovian and Terrestrial exoplanets that works with segmented aperture telescopes. Jovian and Terrestrial planets require at least 10-9 and 10-10 image plane contrasts, respectively, within the spectral bandpass and thus require a nearly achromatic π-phase difference between the arms of the interferometer. An achromatic π-phase shift can be achieved by several techniques, including sequential angled thick glass plates of varying dispersive materials, distributed thin-film multilayer coatings, or techniques that leverage the polarization-dependent phase shift of total-internal reflections. Herein we describe two implementations of such techniques: sequential thick glass plates and Fresnel rhomb prisms. A viable technique must achieve the achromatic phase shift while simultaneously minimizing the intensity difference, chromatic beam spread and polarization variation between the interferometer arms. In this paper we describe the above implementations and report on the trades associated with each technique that will lead to an implementation of the most promising one in Goddard's Visible Nulling Coronagraph (VNC).

Detection of long nulls in PSR B1706-16, a pulsar with large timing irregularities

Science.gov (United States)

Naidu, Arun; Joshi, Bhal Chandra; Manoharan, P. K.; Krishnakumar, M. A.

2018-04-01

Single pulse observations, characterizing in detail, the nulling behaviour of PSR B1706-16 are being reported for the first time in this paper. Our regular long duration monitoring of this pulsar reveals long nulls of 2-5 h with an overall nulling fraction of 31 ± 2 per cent. The pulsar shows two distinct phases of emission. It is usually in an active phase, characterized by pulsations interspersed with shorter nulls, with a nulling fraction of about 15 per cent, but it also rarely switches to an inactive phase, consisting of long nulls. The nulls in this pulsar are concurrent between 326.5 and 610 MHz. Profile mode changes accompanied by changes in fluctuation properties are seen in this pulsar, which switches from mode A before a null to mode B after the null. The distribution of null durations in this pulsar is bimodal. With its occasional long nulls, PSR B1706-16 joins the small group of intermediate nullers, which lie between the classical nullers and the intermittent pulsars. Similar to other intermediate nullers, PSR B1706-16 shows high timing noise, which could be due to its rare long nulls if one assumes that the slowdown rate during such nulls is different from that during the bursts.

Euclidean null controllability of nonlinear infinite delay systems with ...

African Journals Online (AJOL)

Sufficient conditions for the Euclidean null controllability of non-linear delay systems with time varying multiple delays in the control and implicit derivative are derived. If the uncontrolled system is uniformly asymptotically stable and if the control system is controllable, then the non-linear infinite delay system is Euclidean null ...

Visual and Plastic Arts in Teaching Literacy: Null Curricula?

Science.gov (United States)

Wakeland, Robin Gay

2010-01-01

Visual and plastic arts in contemporary literacy instruction equal null curricula. Studies show that painting and sculpture facilitate teaching reading and writing (literacy), yet such pedagogy has not been formally adopted into USA curriculum. An example of null curriculum can be found in late 19th - early 20th century education the USA…

On the Robinson theorem and shearfree geodesic null congruences

International Nuclear Information System (INIS)

Tafel, J.

1985-01-01

Null electromagnetic fields and shearfree geodesic null congruences in curved and flat spacetimes are studied. We point out some mathematical problems connected with the validity of the Robinson theorem. The problem of finding nonanalytic twisting congruences in the Minkowski space is reduced to the construction of holomorphic functions with specific boundary conditions. (orig.)

Regional expression of aquaporins 1, 4, and 9 in the brain during pregnancy

NARCIS (Netherlands)

Wiegman, Marchien J.; Bullinger, Lisa V.; Kohlmeyer, Meghan M.; Hunter, Timothy C.; Cipolla, Marilyn J.

Pregnancy is a state of physiologic adaptation, with significant changes in cardiovascular, renal, and hemodynamic systems. Aquaporins (AQPs) may play a role in facilitating these changes. Mile AQP expression has been assessed in several organs during pregnancy, little is known about its expression

Losses at magnetic nulls in pulsed-power transmission line systems

International Nuclear Information System (INIS)

Mendel, C.W. Jr.; Pointon, T.D.; Savage, M.E.; Seidel, D.B.; Magne, I.; Vezinet, R.

2006-01-01

Pulsed-power systems operating in the terawatt regime must deal with large electron flows in vacuum transmission lines. In most parts of these transmission lines the electrons are constrained by the self-magnetic field to flow parallel to the conductors. In very low impedance systems, such as those used to drive Z-pinch radiation sources, the currents from multiple transmission lines are added together. This addition necessarily involves magnetic nulls that connect the positive and negative electrodes. The resultant local loss of magnetic insulation results in electron losses at the anode in the vicinity of the nulls. The lost current due to the magnetic null might or might not be appreciable. In some cases the lost current due to the null is not large, but is spatially localized, and may create a gas and plasma release from the anode that can lead to an excessive loss, and possibly to catastrophic damage to the hardware. In this paper we describe an analytic model that uses one geometric parameter (aside from straightforward hardware size measurements) that determines the loss to the anode, and the extent of the loss region when the driving source and load are known. The parameter can be calculated in terms of the magnetic field in the region of the null calculated when no electron flow is present. The model is compared to some experimental data, and to simulations of several different hardware geometries, including some cases with multiple nulls, and unbalanced feeds

Current singularities at finitely compressible three-dimensional magnetic null points

International Nuclear Information System (INIS)

Pontin, D.I.; Craig, I.J.D.

2005-01-01

The formation of current singularities at line-tied two- and three-dimensional (2D and 3D, respectively) magnetic null points in a nonresistive magnetohydrodynamic environment is explored. It is shown that, despite the different separatrix structures of 2D and 3D null points, current singularities may be initiated in a formally equivalent manner. This is true no matter whether the collapse is triggered by flux imbalance within closed, line-tied null points or driven by externally imposed velocity fields in open, incompressible geometries. A Lagrangian numerical code is used to investigate the finite amplitude perturbations that lead to singular current sheets in collapsing 2D and 3D null points. The form of the singular current distribution is analyzed as a function of the spatial anisotropy of the null point, and the effects of finite gas pressure are quantified. It is pointed out that the pressure force, while never stopping the formation of the singularity, significantly alters the morphology of the current distribution as well as dramatically weakening its strength. The impact of these findings on 2D and 3D magnetic reconnection models is discussed

Null but not void: considerations for hypothesis testing.

Science.gov (United States)

Shaw, Pamela A; Proschan, Michael A

2013-01-30

Standard statistical theory teaches us that once the null and alternative hypotheses have been defined for a parameter, the choice of the statistical test is clear. Standard theory does not teach us how to choose the null or alternative hypothesis appropriate to the scientific question of interest. Neither does it tell us that in some cases, depending on which alternatives are realistic, we may want to define our null hypothesis differently. Problems in statistical practice are frequently not as pristinely summarized as the classic theory in our textbooks. In this article, we present examples in statistical hypothesis testing in which seemingly simple choices are in fact rich with nuance that, when given full consideration, make the choice of the right hypothesis test much less straightforward. Published 2012. This article is a US Government work and is in the public domain in the USA.

Vacuum non-expanding horizons and shear-free null geodesic congruences

International Nuclear Information System (INIS)

Adamo, T M; Newman, E T

2009-01-01

We investigate the geometry of a particular class of null surfaces in spacetime called vacuum non-expanding horizons (NEHs). Using the spin-coefficient equation, we provide a complete description of the horizon geometry, as well as fixing a canonical choice of null tetrad and coordinates on a NEH. By looking for particular classes of null geodesic congruences which live exterior to NEHs but have the special property that their shear vanishes at the intersection with the horizon, a good cut formalism for NEHs is developed which closely mirrors asymptotic theory. In particular, we show that such null geodesic congruences are generated by arbitrary choice of a complex worldline in a complex four-dimensional space, each such choice induces a CR structure on the horizon, and a particular worldline (and hence CR structure) may be chosen by transforming to a privileged tetrad frame.

High-contrast Nulling Interferometry Techniques Project

Data.gov (United States)

National Aeronautics and Space Administration — "We are developing rotating-baseline nulling-interferometry techniques and algorithms on the single-aperture Hale and Keck telescopes at near-infrared wavelengths,...

A model for electron currents near a field null

International Nuclear Information System (INIS)

Stark, R.A.; Miley, G.H.

1987-01-01

The fluid approximation is invalid near a field null, since the local electron orbit size and the magnetic scale length are comparable. To model the electron currents in this region we propose a single equation of motion describing the bulk electron dynamics. The equation applies to the plasma within one thermal orbit size of the null. The region is treated as unmagnetized; electrons are accelerated by the inductive electric field and drag on ions; damping is provided by viscosity due to electrons and collisions with ions. Through variational calculations and a particle tracking code for electrons, the size of the terms in the equation of motion have been estimated. The resulting equation of motion combines with Faraday's Law to produce a governing equation which implicitly contains the self inductive field of the electrons. This governing equation predicts that viscosity prevents complete cancellation of the ion current density by the electrons in the null region. Thus electron dynamics near the field null should not prevent the formation and deepening of field reversal using neutral-beam injection

ISCO and Principal Null Congruences in Extremal Kerr Spacetime

International Nuclear Information System (INIS)

Pradhan, Parthapratim

2012-01-01

The effective potential in universal like coordinates(U, V, θ, φ), which are smooth across the event horizon is derived and investigated the ISCO(Innermost Stable Circular Orbits) explicitly in these coordinates for extremal Kerr spacetime. Extremization of the effective potential for timelike circular orbit shows that the existence of a stable circular geodesics in the extremal spacetime for direct orbit, precisely on the event horizon in terms of the radial coordinate which coincides with the principal null geodesic congruences of the event horizon. These null geodesic congruences mold themselves to the spacetime curvature in such a way that Weyl conformal tensor and its dual are vanished, that is why they are in-fact doubly degenerate principal null congruences.

Increased trabecular bone and improved biomechanics in an osteocalcin-null rat model created by CRISPR/Cas9 technology

Directory of Open Access Journals (Sweden)

Laura J. Lambert

2016-10-01

Full Text Available Osteocalcin, also known as bone γ-carboxyglutamate protein (Bglap, is expressed by osteoblasts and is commonly used as a clinical marker of bone turnover. A mouse model of osteocalcin deficiency has implicated osteocalcin as a mediator of changes to the skeleton, endocrine system, reproductive organs and central nervous system. However, differences between mouse and human osteocalcin at both the genome and protein levels have challenged the validity of extrapolating findings from the osteocalcin-deficient mouse model to human disease. The rat osteocalcin (Bglap gene locus shares greater synteny with that of humans. To further examine the role of osteocalcin in disease, we created a rat model with complete loss of osteocalcin using the CRISPR/Cas9 system. Rat osteocalcin was modified by injection of CRISPR/Cas9 mRNA into the pronuclei of fertilized single cell Sprague-Dawley embryos, and animals were bred to homozygosity and compound heterozygosity for the mutant alleles. Dual-energy X-ray absorptiometry (DXA, glucose tolerance testing (GTT, insulin tolerance testing (ITT, microcomputed tomography (µCT, and a three-point break biomechanical assay were performed on the excised femurs at 5 months of age. Complete loss of osteocalcin resulted in bones with significantly increased trabecular thickness, density and volume. Cortical bone volume and density were not increased in null animals. The bones had improved functional quality as evidenced by an increase in failure load during the biomechanical stress assay. Differences in glucose homeostasis were observed between groups, but there were no differences in body weight or composition. This rat model of complete loss of osteocalcin provides a platform for further understanding the role of osteocalcin in disease, and it is a novel model of increased bone formation with potential utility in osteoporosis and osteoarthritis research.

Glutathione S-transferase M1-null genotype as risk factor for SOS in oxaliplatin-treated patients with metastatic colorectal cancer.

Science.gov (United States)

Vreuls, C P H; Olde Damink, S W M; Koek, G H; Winstanley, A; Wisse, E; Cloots, R H E; van den Broek, M A J; Dejong, C H C; Bosman, F T; Driessen, A

2013-02-19

Oxaliplatin is used as a neo-adjuvant therapy in hepatic colorectal carcinoma metastasis. This treatment has significant side effects, as oxaliplatin is toxic to the sinusoidal endothelial cells and can induce sinusoidal obstruction syndrome (SOS), which is related to decreased overall survival. Glutathione has an important role in the defence system, catalysed by glutathione S-transferase (GST), including two non-enzyme producing polymorphisms (GSTM1-null and GSTT1-null). We hypothesise that patients with a non-enzyme producing polymorphism have a higher risk of developing toxic injury owing to oxaliplatin. In the nontumour-bearing liver, the presence of SOS was studied histopathologically. The genotype was determined by a semi-nested PCR. Thirty-two of the 55 (58%) patients showed SOS lesions, consisting of 27% mild, 22% moderate and 9% severe lesions. The GSTM1-null genotype was present in 25 of the 55 (46%). Multivariate analysis showed that the GSTM1-null genotype significantly correlated with the presence of (moderate-severe) SOS (P=0.026). The GSTM1-null genotype is an independent risk factor for SOS. This finding allows us, in association with other risk factors, to conceive a potential risk profile predicting whether the patient is at risk of developing SOS, before starting oxaliplatin, and subsequently might result in adjustment of treatment.

Contribution of aquaporin 9 and multidrug resistance-associated protein 2 to differential sensitivity to arsenite between primary cultured chorion and amnion cells prepared from human fetal membranes

International Nuclear Information System (INIS)

Yoshino, Yuta; Yuan, Bo; Kaise, Toshikazu; Takeichi, Makoto; Tanaka, Sachiko; Hirano, Toshihiko; Kroetz, Deanna L.; Toyoda, Hiroo

2011-01-01

Arsenic trioxide (arsenite, As III ) has shown a remarkable clinical efficacy, whereas its side effects are still a serious concern. Therefore, it is critical to understand the effects of As III on human-derived normal cells for revealing the mechanisms underlying these side effects. We examined the effects of As III on primary cultured chorion (C) and amnion (A) cells prepared from human fetal membranes. A significant dose-dependent As III -mediated cytotoxicity was observed in the C-cells accompanied with an increase of lactate dehydrogenase (LDH) release. Higher concentrations of As III were required for the A-cells to show cytotoxicity and LDH release, suggesting that the C-cells were more sensitive to As III than the A-cells. The expression levels of aquaporin 9 (AQP9) were approximately 2 times higher in the C-cells than those in the A-cells. Both intracellular arsenic accumulation and its cytotoxicity in the C-cells were significantly abrogated by sorbitol, a competitive AQP9 inhibitor, in a dose-dependent manner. The protein expression levels of multidrug resistance-associated protein (MRP) 2 were downregulated by As III in the C-cells, but not in the A-cells. No significant differences in the expression levels of MRP1 were observed between C- and A-cells. The protein expression of P-glycoprotein (P-gp) was hardly detected in both cells, although a detectable amount of its mRNA was observed. Cyclosporine A, a broad-spectrum inhibitor for ABC transporters, and MK571, a MRP inhibitor, but not PGP-4008, a P-gp specific inhibitor, potently sensitized both cells to As III -mediated cytotoxicity. These results suggest that AQP9 and MRP2 are involved in controlling arsenic accumulation in these normal cells, which then contribute to differential sensitivity to As III cytotoxicity between these cells. -- Highlights: ► Examination of effect of As III on primary cultured chorion (C) and amnion (A) cells. ► Dose-dependent As III -mediated cytotoxicity in C

Singular Null Hypersurfaces in General Relativity

International Nuclear Information System (INIS)

Dray, T

2006-01-01

Null hypersurfaces are a mathematical consequence of the Lorentzian signature of general relativity; singularities in mathematical models usually indicate where the interesting physics takes place. This book discusses what happens when you combine these ideas. Right from the preface, this is a no-nonsense book. There are two principal approaches to singular shells, one distributional and the other 'cut and paste'; both are treated in detail. A working knowledge of GR is assumed, including familiarity with null tetrads, differential forms, and 3 + 1 decompositions. Despite my own reasonably extensive, closely related knowledge, there was material unfamiliar to me already in chapter 3, although I was reunited with some old friends in later chapters. The exposition is crisp, with a minimum of transition from chapter to chapter. In fact, my main criticism is that there is no clear statement of the organization of the book, nor is there an index. Everything is here, and the story is compelling if you know what to look for, although it is less easy to follow the story if you are not already familiar with it. But this is really a book for experts, and the authors certainly qualify, having played a significant role in developing and extending the results they describe. It is also entirely appropriate that the book is dedicated to Werner Israel, who pioneered the thin-shell approach to (non-null) singular surfaces and later championed the use of similar methods for analysing null shells. After an introductory chapter on impulsive signals, the authors show how the Bianchi identities can be used to classify spacetimes with singular null hypersurfaces. This approach, due to the authors, generalizes the framework originally proposed by Penrose. While astrophysical applications are discussed only briefly, the authors point out that detailed physical characteristics of signals from isolated sources can be determined in this manner. In particular, they describe the behaviour of

Megalin-mediated specific uptake of chitosan/siRNA nanoparticles in mouse kidney proximal tubule epithelial cells enables AQP1 gene silencing.

Science.gov (United States)

Gao, Shan; Hein, San; Dagnæs-Hansen, Frederik; Weyer, Kathrin; Yang, Chuanxu; Nielsen, Rikke; Christensen, Erik I; Fenton, Robert A; Kjems, Jørgen

2014-01-01

RNAi-based strategies provide a great therapeutic potential for treatment of various human diseases including kidney disorders, but face the challenge of in vivo delivery and specific targeting. The chitosan delivery system has previously been shown to target siRNA specifically to the kidneys in mice when administered intravenously. Here we confirm by 2D and 3D bioimaging that chitosan formulated siRNA is retained in the kidney for more than 48 hours where it accumulates in proximal tubule epithelial cells (PTECs), a process that was strongly dependent on the molecular weight of chitosan. Chitosan/siRNA nanoparticles, administered to chimeric mice with conditional knockout of the megalin gene, distributed almost exclusively in cells that expressed megalin, implying that the chitosan/siRNA particle uptake was mediated by a megalin-dependent endocytotic pathway. Knockdown of the water channel aquaporin 1 (AQP1) by up to 50% in PTECs was achieved utilizing the systemic i.v. delivery of chitosan/AQP1 siRNA in mice. In conclusion, specific targeting PTECs with the chitosan nanoparticle system may prove to be a useful strategy for knockdown of specific genes in PTECs, and provides a potential therapeutic strategy for treating various kidney diseases.

Averaged null energy condition and difference inequalities in quantum field theory

International Nuclear Information System (INIS)

Yurtsever, U.

1995-01-01

For a large class of quantum states, all local (pointwise) energy conditions widely used in relativity are violated by the renormalized stress-energy tensor of a quantum field. In contrast, certain nonlocal positivity constraints on the quantum stress-energy tensor might hold quite generally, and this possibility has received considerable attention in recent years. In particular, it is now known that the averaged null energy condition, the condition that the null-null component of the stress-energy tensor integrated along a complete null geodesic is non-negative for all states, holds quite generally in a wide class of spacetimes for a minimally coupled scalar field. Apart from the specific class of spacetimes considered (mainly two-dimensional spacetimes and four-dimensional Minkowski space), the most significant restriction on this result is that the null geodesic over which the average is taken must be achronal. Recently, Ford and Roman have explored this restriction in two-dimensional flat spacetime, and discovered that in a flat cylindrical space, although the stress energy tensor itself fails to satisfy the averaged null energy condition (ANEC) along the (nonachronal) null geodesics, when the ''Casimir-vacuum'' contribution is subtracted from the stress-energy the resulting tensor does satisfy the ANEC inequality. Ford and Roman name this class of constraints on the quantum stress-energy tensor ''difference inequalities.'' Here I give a proof of the difference inequality for a minimally coupled massless scalar field in an arbitrary (globally hyperbolic) two-dimensional spacetime, using the same techniques as those we relied on to prove the ANEC in an earlier paper with Wald. I begin with an overview of averaged energy conditions in quantum field theory

Sequential weak continuity of null Lagrangians at the boundary

Czech Academy of Sciences Publication Activity Database

Kalamajska, A.; Kraemer, S.; Kružík, Martin

2014-01-01

Roč. 49, 3/4 (2014), s. 1263-1278 ISSN 0944-2669 R&D Projects: GA ČR GAP201/10/0357 Institutional support: RVO:67985556 Keywords : null Lagrangians * nonhomogeneous nonlinear mappings * sequential weak/in measure continuity Subject RIV: BA - General Mathematics Impact factor: 1.518, year: 2014 http://library.utia.cas.cz/separaty/2013/MTR/kruzik-sequential weak continuity of null lagrangians at the boundary.pdf

A parameter set for a double-null DEMO reactor

International Nuclear Information System (INIS)

Cooke, P.I.H.

1987-01-01

The present study is aimed at commenting on the reactor-relevance of the design principles and technology being proposed for NET. The authors propose that a double-null device serve as a basis for a NET-based demonstration reactor. Calculations are carried out to determine the parameter set for reactors based on the double-null NET design, and the results are presented in tabular form. (U.K.)

Are eikonal quasinormal modes linked to the unstable circular null geodesics?

Directory of Open Access Journals (Sweden)

R.A. Konoplya

2017-08-01

Full Text Available In Cardoso et al. [6] it was claimed that quasinormal modes which any stationary, spherically symmetric and asymptotically flat black hole emits in the eikonal regime are determined by the parameters of the circular null geodesic: the real and imaginary parts of the quasinormal mode are multiples of the frequency and instability timescale of the circular null geodesics respectively. We shall consider asymptotically flat black hole in the Einstein–Lovelock theory, find analytical expressions for gravitational quasinormal modes in the eikonal regime and analyze the null geodesics. Comparison of the both phenomena shows that the expected link between the null geodesics and quasinormal modes is violated in the Einstein–Lovelock theory. Nevertheless, the correspondence exists for a number of other cases and here we formulate its actual limits.

Are eikonal quasinormal modes linked to the unstable circular null geodesics?

Science.gov (United States)

Konoplya, R. A.; Stuchlík, Z.

2017-08-01

In Cardoso et al. [6] it was claimed that quasinormal modes which any stationary, spherically symmetric and asymptotically flat black hole emits in the eikonal regime are determined by the parameters of the circular null geodesic: the real and imaginary parts of the quasinormal mode are multiples of the frequency and instability timescale of the circular null geodesics respectively. We shall consider asymptotically flat black hole in the Einstein-Lovelock theory, find analytical expressions for gravitational quasinormal modes in the eikonal regime and analyze the null geodesics. Comparison of the both phenomena shows that the expected link between the null geodesics and quasinormal modes is violated in the Einstein-Lovelock theory. Nevertheless, the correspondence exists for a number of other cases and here we formulate its actual limits.

Modular Hamiltonians on the null plane and the Markov property of the vacuum state

Science.gov (United States)

Casini, Horacio; Testé, Eduardo; Torroba, Gonzalo

2017-09-01

We compute the modular Hamiltonians of regions having the future horizon lying on a null plane. For a CFT this is equivalent to regions with a boundary of arbitrary shape lying on the null cone. These Hamiltonians have a local expression on the horizon formed by integrals of the stress tensor. We prove this result in two different ways, and show that the modular Hamiltonians of these regions form an infinite dimensional Lie algebra. The corresponding group of unitary transformations moves the fields on the null surface locally along the null generators with arbitrary null line dependent velocities, but act non-locally outside the null plane. We regain this result in greater generality using more abstract tools on the algebraic quantum field theory. Finally, we show that modular Hamiltonians on the null surface satisfy a Markov property that leads to the saturation of the strong sub-additive inequality for the entropies and to the strong super-additivity of the relative entropy.

sirt1-null mice develop an autoimmune-like condition

International Nuclear Information System (INIS)

Sequeira, Jedon; Boily, Gino; Bazinet, Stephanie; Saliba, Sarah; He Xiaohong; Jardine, Karen; Kennedy, Christopher; Staines, William; Rousseaux, Colin; Mueller, Rudi; McBurney, Michael W.

2008-01-01

The sirt1 gene encodes a protein deacetylase with a broad spectrum of reported substrates. Mice carrying null alleles for sirt1 are viable on outbred genetic backgrounds so we have examined them in detail to identify the biological processes that are dependent on SIRT1. Sera from adult sirt1-null mice contain antibodies that react with nuclear antigens and immune complexes become deposited in the livers and kidneys of these animals. Some of the sirt1-null animals develop a disease resembling diabetes insipidus when they approach 2 years of age although the relationship to the autoimmunity remains unclear. We interpret these observations as consistent with a role for SIRT1 in sustaining normal immune function and in this way delaying the onset of autoimmune disease

Null point of discrimination in crustacean polarisation vision.

Science.gov (United States)

How, Martin J; Christy, John; Roberts, Nicholas W; Marshall, N Justin

2014-07-15

The polarisation of light is used by many species of cephalopods and crustaceans to discriminate objects or to communicate. Most visual systems with this ability, such as that of the fiddler crab, include receptors with photopigments that are oriented horizontally and vertically relative to the outside world. Photoreceptors in such an orthogonal array are maximally sensitive to polarised light with the same fixed e-vector orientation. Using opponent neural connections, this two-channel system may produce a single value of polarisation contrast and, consequently, it may suffer from null points of discrimination. Stomatopod crustaceans use a different system for polarisation vision, comprising at least four types of polarisation-sensitive photoreceptor arranged at 0, 45, 90 and 135 deg relative to each other, in conjunction with extensive rotational eye movements. This anatomical arrangement should not suffer from equivalent null points of discrimination. To test whether these two systems were vulnerable to null points, we presented the fiddler crab Uca heteropleura and the stomatopod Haptosquilla trispinosa with polarised looming stimuli on a modified LCD monitor. The fiddler crab was less sensitive to differences in the degree of polarised light when the e-vector was at -45 deg than when the e-vector was horizontal. In comparison, stomatopods showed no difference in sensitivity between the two stimulus types. The results suggest that fiddler crabs suffer from a null point of sensitivity, while stomatopods do not. © 2014. Published by The Company of Biologists Ltd.

Logarithmic corrections to gravitational entropy and the null energy condition

Energy Technology Data Exchange (ETDEWEB)

Parikh, Maulik, E-mail: maulik.parikh@asu.edu; Svesko, Andrew

2016-10-10

Using a relation between the thermodynamics of local horizons and the null energy condition, we consider the effects of quantum corrections to the gravitational entropy. In particular, we find that the geometric form of the null energy condition is not affected by the inclusion of logarithmic corrections to the Bekenstein–Hawking entropy.

Yang-Mills theory in null path space

International Nuclear Information System (INIS)

Kent, S.L.

1982-01-01

A reformulation of classical GL(n,c) Yang-Mills theory is presented. The reformulation is in terms of a single matrix-valued function G on a six-dimensional subspace of the space of paths in Minkowski space, M. This subspace is defined as the null paths beginning at each point, (X/sup a/), of M and ending at future null infinity. A convenient parametrization of these paths is to give the Minkowski coordinates x/sup a/ of the starting point and the (complex) stereographic coordinates (xi, antixi) on S 2 which label the light cone generators of x/sup a/. A path is thus labeled by (x/sup a/,xi, antixi). The function G(x/sup a/,xi, antixi) is defined by the parallel propagation (with a given connection) of n linearly independent fiber vectors from x/sup a/ to null infinity along the (xi, antixi) generator. From knowledge of G(x/sup a/,xi, antixi) the connection one-form γ/sub a/ at the point x/sup a/ can be obtained is shown. Furthermore how the vacuum Yang-Mills equations can be imposed on the G is shown. This results in a rather complicated integro-differential equation for G which involves the characteristic initial data (essentially the radiation field) acting as the driving term. Two simple special cases are immediately obtainable; in the case of self-dual (or anti-self dual) fields the author obtains a simple derivation of the Sparling equation, namely delta G = -GA, while for Abelian (Maxwell) theories obtained the equation delta anti delta log G = -anti delta A-anti delta A, where A and its conjugate anti A are the characteristic free data given on null infinity. The latter equation is equivalent to the vacuum Maxwell equations

Logarithmic corrections to gravitational entropy and the null energy condition

Directory of Open Access Journals (Sweden)

Maulik Parikh

2016-10-01

Full Text Available Using a relation between the thermodynamics of local horizons and the null energy condition, we consider the effects of quantum corrections to the gravitational entropy. In particular, we find that the geometric form of the null energy condition is not affected by the inclusion of logarithmic corrections to the Bekenstein–Hawking entropy.

Maxwell fields and shear-free null geodesic congruences

International Nuclear Information System (INIS)

Newman, Ezra T

2004-01-01

We study and report on the class of vacuum Maxwell fields in Minkowski space that possess a non-degenerate, diverging, principal null vector field (null eigenvector field of the Maxwell tensor) that is tangent to a shear-free null geodesics congruence. These congruences can be either surface forming (the tangent vectors being proportional to gradients) or not, i.e., the twisting congruences. In the non-twisting case, the associated Maxwell fields are precisely the Lienard-Wiechert fields, i.e., those Maxwell fields arising from an electric monopole moving on an arbitrary worldline. The null geodesic congruence is given by the generators of the light-cones with apex on the worldline. The twisting case is much richer, more interesting and far more complicated. In a twisting subcase, where our main interests lie, the following strange interpretation can be given. If we allow the real Minkowski space to be complexified so that the real Minkowski coordinates x a take complex values, i.e., x a → z a = x a + iy a with complex metric g η ab dz a dz b , the real vacuum Maxwell equations can be extended into the complex space and rewritten as curl W=i W radical, div W=0 with W=E+iB. This subcase of Maxwell fields can then be extended into the complex space so as to have as source, a complex analytic worldline, i.e., to now become complex Lienard-Wiechart fields. When viewed as real fields on the real Minkowski space (z a = x a ), they possess a real principal null vector that is shear-free but twisting and diverging. The twist is a measure of how far the complex worldline is from the real 'slice'. Most Maxwell fields in this subcase are asymptotically flat with a time-varying set of electric and magnetic moments, all depending on the complex displacements and the complex velocities

The data-driven null models for information dissemination tree in social networks

Science.gov (United States)

Zhang, Zhiwei; Wang, Zhenyu

2017-10-01

For the purpose of detecting relatedness and co-occurrence between users, as well as the distribution features of nodes in spreading path of a social network, this paper explores topological characteristics of information dissemination trees (IDT) that can be employed indirectly to probe the information dissemination laws within social networks. Hence, three different null models of IDT are presented in this article, including the statistical-constrained 0-order IDT null model, the random-rewire-broken-edge 0-order IDT null model and the random-rewire-broken-edge 2-order IDT null model. These null models firstly generate the corresponding randomized copy of an actual IDT; then the extended significance profile, which is developed by adding the cascade ratio of information dissemination path, is exploited not only to evaluate degree correlation of two nodes associated with an edge, but also to assess the cascade ratio of different length of information dissemination paths. The experimental correspondences of the empirical analysis for several SinaWeibo IDTs and Twitter IDTs indicate that the IDT null models presented in this paper perform well in terms of degree correlation of nodes and dissemination path cascade ratio, which can be better to reveal the features of information dissemination and to fit the situation of real social networks.

NH3 and NH4+ permeability in aquaporin-expressing Xenopus oocytes

DEFF Research Database (Denmark)

Holm, Lars M.; Jahn, Thomas Paul; Møller, Anders Laurell Blom

2005-01-01

We have shown recently, in a yeast expression system, that some aquaporins are permeable to ammonia. In the present study, we expressed the mammalian aquaporins AQP8, AQQP9, AQP3, AQP1 and a plant aquaporin TIP2;1 in Xenopus oocytes to study the transport of ammonia (NH3) and ammonium (NH4+) under...... inwards currents carried by NH4+. This conductivity increased as a sigmoid function of external [NH3]: for AQP8 at a bath pH (pH(e)) of 6.5, the conductance was abolished, at pH(e) 7.4 it was half maximal and at pH(e) 7.8 it saturated. NY4+ influx was associated with oocyte swelling. In comparison, native...... oocytes as well as AQP1 and tip2;1-expressing oocytes showed small currents that were associated with small and even negative volume changes. We conclude that AQP8, AQP9, AQP3, and TIP2;1, apart from being water channels, also support significant fluxes of NH3. These aquaporins could support NH4...

Effects of dietary nitrogen concentration on messenger RNA expression and protein abundance of urea transporter-B and aquaporins in ruminal papillae from lactating Holstein cows

DEFF Research Database (Denmark)

Røjen, Betina Amdisen; Poulsen, Søren Brandt; Theil, Peter Kappel

2011-01-01

To test the hypothesis that dietary N concentrations affect gut epithelial urea transport by modifying the expression of urea transporter B (UT-B) and aquaporins (AQP), the mRNA expression and protein abundance of UT-B and AQP3, AQP7, AQP8, and AQP10 were investigated in ruminal papillae from 9...... lactating dairy cows. Ruminal papillae were harvested from cows fed low N (12.9% crude protein) and high N (17.1% crude protein) diets in a crossover design with 21-d periods. The mRNA expression was determined by real-time reverse transcription-PCR and protein abundance by immunoblotting. The m......RNA expression of UT-B was not affected by dietary treatment, whereas mRNA expression of AQP3, 7, and 10 were greater in the high N compared with the low N fed cows. Using peptide-derived rabbit antibodies to cow AQP3, 7, and 8, immunoblotting revealed bands of approximately 27, 27, and 24 kDa in ruminal...

Water fluxes through aquaporin-9 prime epithelial cells for rapid wound healing

DEFF Research Database (Denmark)

Karlsson, T.; Lagerholm, B. C.; Vikstrom, E.

2013-01-01

Cells move along surfaces both as single cells and multi-cellular units. Recent research points toward pivotal roles for water flux through aquaporins (AQPs) in single cell migration. Their expression is known to facilitate this process by promoting rapid shape changes. However, little is known...... wound healing based on AQP-induced swelling and expansion of the monolayer. (C) 2012 Elsevier Inc. All rights reserved....

On the geometry of null congruences in general relativity

International Nuclear Information System (INIS)

Ahsan, Zafar; Malik, N.P.

1977-01-01

Some theorems for the null congruences within the framework of general theory of relativity are given. These theorems are important in themselves as they illustrate the geometric meaning of the spin coefficients. The newly developed Geroch-Held-Penrose (GHP) formalism has been used throughout the investigations. The salient features of GHP formalism that are necessary for the present work are given and these techniques are applied to a pair of null congruences C(l) and C(n). (author)

pyNSMC: A Python Module for Null-Space Monte Carlo Uncertainty Analysis

Science.gov (United States)

White, J.; Brakefield, L. K.

2015-12-01

The null-space monte carlo technique is a non-linear uncertainty analyses technique that is well-suited to high-dimensional inverse problems. While the technique is powerful, the existing workflow for completing null-space monte carlo is cumbersome, requiring the use of multiple commandline utilities, several sets of intermediate files and even a text editor. pyNSMC is an open-source python module that automates the workflow of null-space monte carlo uncertainty analyses. The module is fully compatible with the PEST and PEST++ software suites and leverages existing functionality of pyEMU, a python framework for linear-based uncertainty analyses. pyNSMC greatly simplifies the existing workflow for null-space monte carlo by taking advantage of object oriented design facilities in python. The core of pyNSMC is the ensemble class, which draws and stores realized random vectors and also provides functionality for exporting and visualizing results. By relieving users of the tedium associated with file handling and command line utility execution, pyNSMC instead focuses the user on the important steps and assumptions of null-space monte carlo analysis. Furthermore, pyNSMC facilitates learning through flow charts and results visualization, which are available at many points in the algorithm. The ease-of-use of the pyNSMC workflow is compared to the existing workflow for null-space monte carlo for a synthetic groundwater model with hundreds of estimable parameters.

Positive, negative, or null? The effects of maternal incarceration on children's behavioral problems.

Science.gov (United States)

Wildeman, Christopher; Turney, Kristin

2014-06-01

We use data from the Fragile Families and Child Wellbeing Study to consider the effects of maternal incarceration on 21 caregiver- and teacher-reported behavioral problems among 9-year-old children. The results suggest three primary conclusions. First, children of incarcerated mothers are a disadvantaged group that exhibit high levels of caregiver- and teacher-reported behavioral problems. Second, after we adjust for selection, the effects of maternal incarceration on children's behavioral problems are consistently null (for 19 of 21 outcomes) and rarely positive (1 of 21) or negative (1 of 21), suggesting that the poor outcomes of these children are driven by disadvantages preceding maternal incarceration rather than incarceration. These effects, however, vary across race/ethnicity, with maternal incarceration diminishing caregiver-reported behavioral problems among non-Hispanic whites. Finally, in models considering both maternal and paternal incarceration, paternal incarceration is associated with more behavioral problems, which is consistent with previous research and suggests that the null effects of maternal incarceration are not artifacts of our sample or analytic decisions.

Contribution of aquaporin 9 and multidrug resistance-associated protein 2 to differential sensitivity to arsenite between primary cultured chorion and amnion cells prepared from human fetal membranes

Energy Technology Data Exchange (ETDEWEB)

Yoshino, Yuta [Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Yuan, Bo, E-mail: yuanbo@toyaku.ac.jp [Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, 1550 4th St, RH584E Box 2911 San Francisco, CA 94158-2911 (United States); Kaise, Toshikazu [Laboratory of Environmental Chemodynamics, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Takeichi, Makoto [Yoneyama Maternity Hospital, 2-12 Shin-machi, Hachioji, Tokyo 192-0065 (Japan); Tanaka, Sachiko; Hirano, Toshihiko [Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Kroetz, Deanna L. [Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, 1550 4th St, RH584E Box 2911 San Francisco, CA 94158-2911 (United States); Toyoda, Hiroo [Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan)

2011-12-15

Arsenic trioxide (arsenite, As{sup III}) has shown a remarkable clinical efficacy, whereas its side effects are still a serious concern. Therefore, it is critical to understand the effects of As{sup III} on human-derived normal cells for revealing the mechanisms underlying these side effects. We examined the effects of As{sup III} on primary cultured chorion (C) and amnion (A) cells prepared from human fetal membranes. A significant dose-dependent As{sup III}-mediated cytotoxicity was observed in the C-cells accompanied with an increase of lactate dehydrogenase (LDH) release. Higher concentrations of As{sup III} were required for the A-cells to show cytotoxicity and LDH release, suggesting that the C-cells were more sensitive to As{sup III} than the A-cells. The expression levels of aquaporin 9 (AQP9) were approximately 2 times higher in the C-cells than those in the A-cells. Both intracellular arsenic accumulation and its cytotoxicity in the C-cells were significantly abrogated by sorbitol, a competitive AQP9 inhibitor, in a dose-dependent manner. The protein expression levels of multidrug resistance-associated protein (MRP) 2 were downregulated by As{sup III} in the C-cells, but not in the A-cells. No significant differences in the expression levels of MRP1 were observed between C- and A-cells. The protein expression of P-glycoprotein (P-gp) was hardly detected in both cells, although a detectable amount of its mRNA was observed. Cyclosporine A, a broad-spectrum inhibitor for ABC transporters, and MK571, a MRP inhibitor, but not PGP-4008, a P-gp specific inhibitor, potently sensitized both cells to As{sup III}-mediated cytotoxicity. These results suggest that AQP9 and MRP2 are involved in controlling arsenic accumulation in these normal cells, which then contribute to differential sensitivity to As{sup III} cytotoxicity between these cells. -- Highlights: Black-Right-Pointing-Pointer Examination of effect of As{sup III} on primary cultured chorion (C) and amnion

Testing the null hypothesis: the forgotten legacy of Karl Popper?

Science.gov (United States)

Wilkinson, Mick

2013-01-01

Testing of the null hypothesis is a fundamental aspect of the scientific method and has its basis in the falsification theory of Karl Popper. Null hypothesis testing makes use of deductive reasoning to ensure that the truth of conclusions is irrefutable. In contrast, attempting to demonstrate the new facts on the basis of testing the experimental or research hypothesis makes use of inductive reasoning and is prone to the problem of the Uniformity of Nature assumption described by David Hume in the eighteenth century. Despite this issue and the well documented solution provided by Popper's falsification theory, the majority of publications are still written such that they suggest the research hypothesis is being tested. This is contrary to accepted scientific convention and possibly highlights a poor understanding of the application of conventional significance-based data analysis approaches. Our work should remain driven by conjecture and attempted falsification such that it is always the null hypothesis that is tested. The write up of our studies should make it clear that we are indeed testing the null hypothesis and conforming to the established and accepted philosophical conventions of the scientific method.

Null controllability of a cascade system of Schrodinger equations

Directory of Open Access Journals (Sweden)

Marcos Lopez-Garcia

2016-03-01

Full Text Available This article presents a control problem for a cascade system of two linear N-dimensional Schrodinger equations. We address the problem of null controllability by means of a control supported in a region not satisfying the classical geometrical control condition. The proof is based on the application of a Carleman estimate with degenerate weights to each one of the equations and a careful analysis of the system in order to prove null controllability with only one control force.

Increased occurrence of anti-AQP4 seropositivity and unique HLA Class II associations with neuromyelitis optica (NMO), among Muslim Arabs in Israel.

Science.gov (United States)

Brill, Livnat; Mandel, Micha; Karussis, Dimitrios; Petrou, Panayiota; Miller, Keren; Ben-Hur, Tamir; Karni, Arnon; Paltiel, Ora; Israel, Shoshana; Vaknin-Dembinsky, Adi

2016-04-15

Previous studies have revealed different human leukocyte antigen (HLA) associations in multiple sclerosis (MS) and neuromyelitis optica (NMO), further discriminating these two demyelinating pathological conditions. In worldwide analyses, NMO and opticospinal MS are represented at higher proportions among demyelinating conditions in African, East-Asian and Latin American populations. There are currently no data regarding the prevalence of NMO in Middle East Muslims. The population in Israel is diverse in many ways, and includes subpopulations, based on religion and ethnicity; some exhibit genetic homogeneity. In Israel, the incidence of MS is lower in the Muslim population than the Jewish population and Muslims carry different allele frequency distribution of HLA haplotypes. To evaluate the occurrence of anti-AQP4 seropositivity in the Israeli Muslim population among patients with central nervous system (CNS) demyelinating conditions; and to identify the HLA DR and DQ profiles of Muslim Arab Israeli patients with NMO spectrum of diseases (NMOSD). The prevalence of anti-AQP4 seropositivity was analyzed in 342 samples, obtained from patients with various CNS demyelinating conditions and in a validation set of 310 samples. HLA class II alleles (HLA-DRB1 and DQB1) were examined in DNA samples from 35 Israeli Muslim Arabs NMO patients and compared to available data from 74 Israeli Muslim controls. Our data reveal a significantly increased prevalence of anti-AQP4 seropositivity, indicative of NMOSD, in Muslim Arab Israeli patients with initial diagnosis of a CNS demyelinating syndrome. In this population, there was a positive association with the HLA-DRB1*04:04 and HLA-DRB1*10:01 alleles (p=0.03), and a strong negative association with the HLA-DRB1*07 and HLA-DQB1*02:02 alleles (p=0.003, p=0.002). Our findings indicate a possibly increased prevalence of NMOSD in Muslim Arabs in Israel with distinct (positive and negative) HLA associations. Further studies in patients with

THE NATURE OF FLARE RIBBONS IN CORONAL NULL-POINT TOPOLOGY

International Nuclear Information System (INIS)

Masson, S.; Aulanier, G.; Pariat, E.; Schrijver, C. J.

2009-01-01

Flare ribbons are commonly attributed to the low-altitude impact, along the footprints of separatrices or quasi-separatrix layers (QSLs), of particle beams accelerated through magnetic reconnection. If reconnection occurs at a three-dimensional coronal magnetic null point, the footprint of the dome-shaped fan surface would map a closed circular ribbon. This paper addresses the following issues: does the entire circular ribbon brighten simultaneously, as expected because all fan field lines pass through the null point? And since the spine separatrices are singular field lines, do spine-related ribbons look like compact kernels? What can we learn from these observations about current sheet formation and magnetic reconnection in a null-point topology? The present study addresses these questions by analyzing Transition Region and Coronal Explorer and Solar and Heliospheric Observatory/Michelson Doppler Imager observations of a confined flare presenting a circular ribbon. Using a potential field extrapolation, we linked the circular shape of the ribbon with the photospheric mapping of the fan field lines originating from a coronal null point. Observations show that the flare ribbon outlining the fan lines brightens sequentially along the counterclockwise direction and that the spine-related ribbons are elongated. Using the potential field extrapolation as initial condition, we conduct a low-β resistive magnetohydrodynamics simulation of this observed event. We drive the coronal evolution by line-tied diverging boundary motions, so as to emulate the observed photospheric flow pattern associated with some magnetic flux emergence. The numerical analysis allows us to explain several observed features of the confined flare. The vorticity induced in the fan by the prescribed motions causes the spines to tear apart along the fan. This leads to formation of a thin current sheet and induces null-point reconnection. We also find that the null point and its associated topological

The (2, 0) superalgebra, null M-branes and Hitchin's system

Science.gov (United States)

Kucharski, P.; Lambert, N.; Owen, M.

2017-10-01

We present an interacting system of equations with sixteen supersymmetries and an SO(2) × SO(6) R-symmetry where the fields depend on two space and one null dimensions that is derived from a representation of the six-dimensional (2, 0) superalgebra. The system can be viewed as two M5-branes compactified on {S}-^1× T^2 or equivalently as M2-branes on R+× R^2 , where ± refer to null directions. We show that for a particular choice of fields the dynamics can be reduced to motion on the moduli space of solutions to the Hitchin system. We argue that this provides a description of intersecting null M2-branes and is also related by U-duality to a DLCQ description of four-dimensional maximally supersymmetric Yang-Mills.

Vacuum nuller testbed (VNT) performance, characterization and null control: progress report

Science.gov (United States)

Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Madison, Timothy; Bolcar, Matthew R.; Noecker, M. Charley; Kendrick, Stephen; Helmbrecht, Michael

2011-10-01

Herein we report on the development, sensing and control and our first results with the Vacuum Nuller Testbed to realize a Visible Nulling Coronagraph (VNC) for exoplanet coronagraphy. The VNC is one of the few approaches that works with filled, segmented and sparse or diluted-aperture telescope systems. It thus spans a range of potential future NASA telescopes and could be flown as a separate instrument on such a future mission. NASA/Goddard Space Flight Center (GSFC) has a well-established effort to develop VNC technologies, and has developed an incremental sequence of VNC testbeds to advance this approach and the enabling technologies associated with it. We discuss the continued development of the vacuum Visible Nulling Coronagraph testbed (VNT). The VNT is an ultra-stable vibration isolated testbed that operates under closed-loop control within a vacuum chamber. It will be used to achieve an incremental sequence of three visible-light nulling milestones with sequentially higher contrasts of 108, 109, and ideally 1010 at an inner working angle of 2*λ/D. The VNT is based on a modified Mach-Zehnder nulling interferometer, with a "W" configuration to accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters. We discuss the initial laboratory results, the optical configuration, critical technologies and the null sensing and control approach.

Nulling tomography with weak gravitational lensing

International Nuclear Information System (INIS)

Huterer, Dragan; White, Martin

2005-01-01

We explore several strategies of eliminating (or nulling) the small-scale information in weak lensing convergence power spectrum measurements in order to protect against undesirable effects, for example, the effects of baryonic cooling and pressure forces on the distribution of large-scale structures. We selectively throw out the small-scale information in the convergence power spectrum that is most sensitive to the unwanted bias, while trying to retain most of the sensitivity to cosmological parameters. The strategies are effective in the difficult but realistic situations when we are able to guess the form of the contaminating effect only approximately. However, we also find that the simplest scheme of simply not using information from the largest multipoles works about as well as the proposed techniques in most, although not all, realistic cases. We advocate further exploration of nulling techniques and believe that they will find important applications in the weak lensing data mining

Aquaporin expression in the fetal porcine urinary tract changes during gestation

DEFF Research Database (Denmark)

Jakobsen, L K; Trelborg, K; Kingo, P S

2018-01-01

The expression of aquaporins (AQPs) in the fetal porcine urinary tract and its relation to gestational age has not been established. Tissue samples from the renal pelvis, ureter, bladder and urethra were obtained from porcine fetuses. Samples were examined by RT-PCR (AQPs 1-11), QPCR (AQPs positive....... Immunohistochemistry showed AQP1 staining in sub-urothelial vessels at all locations. Western blotting analysis confirmed increased AQP1 protein levels in bladder samples during gestation. Expression levels of AQP1, 3, 5, 9 and 11 in the urinary tract change during gestation, and further studies are needed to provide...

An improved null model for assessing the net effects of multiple stressors on communities.

Science.gov (United States)

Thompson, Patrick L; MacLennan, Megan M; Vinebrooke, Rolf D

2018-01-01

Ecological stressors (i.e., environmental factors outside their normal range of variation) can mediate each other through their interactions, leading to unexpected combined effects on communities. Determining whether the net effect of stressors is ecologically surprising requires comparing their cumulative impact to a null model that represents the linear combination of their individual effects (i.e., an additive expectation). However, we show that standard additive and multiplicative null models that base their predictions on the effects of single stressors on community properties (e.g., species richness or biomass) do not provide this linear expectation, leading to incorrect interpretations of antagonistic and synergistic responses by communities. We present an alternative, the compositional null model, which instead bases its predictions on the effects of stressors on individual species, and then aggregates them to the community level. Simulations demonstrate the improved ability of the compositional null model to accurately provide a linear expectation of the net effect of stressors. We simulate the response of communities to paired stressors that affect species in a purely additive fashion and compare the relative abilities of the compositional null model and two standard community property null models (additive and multiplicative) to predict these linear changes in species richness and community biomass across different combinations (both positive, negative, or opposite) and intensities of stressors. The compositional model predicts the linear effects of multiple stressors under almost all scenarios, allowing for proper classification of net effects, whereas the standard null models do not. Our findings suggest that current estimates of the prevalence of ecological surprises on communities based on community property null models are unreliable, and should be improved by integrating the responses of individual species to the community level as does our

Self-Nulling Beam Combiner Using No External Phase Inverter

Science.gov (United States)

Bloemhof, Eric E.

2010-01-01

A self-nulling beam combiner is proposed that completely eliminates the phase inversion subsystem from the nulling interferometer, and instead uses the intrinsic phase shifts in the beam splitters. Simplifying the flight instrument in this way will be a valuable enhancement of mission reliability. The tighter tolerances on R = T (R being reflection and T being transmission coefficients) required by the self-nulling configuration actually impose no new constraints on the architecture, as two adaptive nullers must be situated between beam splitters to correct small errors in the coatings. The new feature is exploiting the natural phase shifts in beam combiners to achieve the 180 phase inversion necessary for nulling. The advantage over prior art is that an entire subsystem, the field-flipping optics, can be eliminated. For ultimate simplicity in the flight instrument, one might fabricate coatings to very high tolerances and dispense with the adaptive nullers altogether, with all their moving parts, along with the field flipper subsystem. A single adaptive nuller upstream of the beam combiner may be required to correct beam train errors (systematic noise), but in some circumstances phase chopping reduces these errors substantially, and there may be ways to further reduce the chop residuals. Though such coatings are beyond the current state of the art, the mechanical simplicity and robustness of a flight system without field flipper or adaptive nullers would perhaps justify considerable effort on coating fabrication.

Null cone superspace supergravity

International Nuclear Information System (INIS)

Downes-Martin, S.G.

1980-03-01

The null cone formalism is used to derive a 2(N-1) parameter family of constraints for O(N) extended superspace supergravity. The invariance groups of these constraints is analysed and is found to be [subgroup U submanifold] contains GL(4,R) for N = 1, the submanifold being eliminated for N > 1. The invariance group defines non-Weyl rotations on the superbein which combine to form Weyl transformations on the supertangent space metric. The invariance of the supergravity Lagrangian under these transformations is discussed. (Auth.)

High Contrast Vacuum Nuller Testbed (VNT) Contrast, Performance and Null Control

Science.gov (United States)

Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Madison, Timothy; Bolcar, Matthew R.

2012-01-01

Herein we report on our Visible Nulling Coronagraph high-contrast result of 109 contrast averaged over a focal planeregion extending from 14 D with the Vacuum Nuller Testbed (VNT) in a vibration isolated vacuum chamber. TheVNC is a hybrid interferometriccoronagraphic approach for exoplanet science. It operates with high Lyot stopefficiency for filled, segmented and sparse or diluted-aperture telescopes, thereby spanning the range of potential futureNASA flight telescopes. NASAGoddard Space Flight Center (GSFC) has a well-established effort to develop the VNCand its technologies, and has developed an incremental sequence of VNC testbeds to advance this approach and itsenabling technologies. These testbeds have enabled advancement of high-contrast, visible light, nulling interferometry tounprecedented levels. The VNC is based on a modified Mach-Zehnder nulling interferometer, with a W configurationto accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters.We give an overview of the VNT and discuss the high-contrast laboratory results, the optical configuration, criticaltechnologies and null sensing and control.

High contrast vacuum nuller testbed (VNT) contrast, performance, and null control

Science.gov (United States)

Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Madison, Timothy; Bolcar, Matthew R.

2012-09-01

Herein we report on our Visible Nulling Coronagraph high-contrast result of 109 contrast averaged over a focal plane region extending from 1 - 4 λ/D with the Vacuum Nuller Testbed (VNT) in a vibration isolated vacuum chamber. The VNC is a hybrid interferometric/coronagraphic approach for exoplanet science. It operates with high Lyot stop efficiency for filled, segmented and sparse or diluted-aperture telescopes, thereby spanning the range of potential future NASA flight telescopes. NASA/Goddard Space Flight Center (GSFC) has a well-established effort to develop the VNC and its technologies, and has developed an incremental sequence of VNC testbeds to advance this approach and its enabling technologies. These testbeds have enabled advancement of high-contrast, visible light, nulling interferometry to unprecedented levels. The VNC is based on a modified Mach-Zehnder nulling interferometer, with a “W” configuration to accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters. We give an overview of the VNT and discuss the high-contrast laboratory results, the optical configuration, critical technologies and null sensing and control.

Spatial and null infinity via advanced and retarded conformal factors

International Nuclear Information System (INIS)

Hayward, Sean A.

2003-01-01

A new approach to space-time asymptotics is presented, refining Penrose's idea of conformal transformations with infinity represented by the conformal boundary of space-time. It is proposed that the Penrose conformal factor be a product of advanced and retarded conformal factors, which asymptotically relate physical and conformal null coordinates and vanish at future and past null infinity respectively. A refined definition of asymptotic flatness at both spatial and null infinity is given, including that the conformal boundary is locally a light cone, with spatial infinity as the vertex. It is shown how to choose the conformal factors so that this asymptotic light cone is locally a metric light cone. The theory is implemented in the spin-coefficient (or null-tetrad) formalism by a joint transformation of the spin-metric and spin-basis (or metric and tetrad). Asymptotic regularity conditions are proposed, based on the conformal boundary locally being a smoothly embedded metric light cone. These conditions ensure that the Bondi-Sachs energy-flux integrals of ingoing and outgoing gravitational radiation decay at spatial infinity such that the total radiated energy is finite, and that the Bondi-Sachs energy-momentum has a unique limit at spatial infinity, coinciding with the uniquely rendered ADM energy-momentum

Unicorns do exist: a tutorial on "proving" the null hypothesis.

Science.gov (United States)

Streiner, David L

2003-12-01

Introductory statistics classes teach us that we can never prove the null hypothesis; all we can do is reject or fail to reject it. However, there are times when it is necessary to try to prove the nonexistence of a difference between groups. This most often happens within the context of comparing a new treatment against an established one and showing that the new intervention is not inferior to the standard. This article first outlines the logic of "noninferiority" testing by differentiating between the null hypothesis (that which we are trying to nullify) and the "nill" hypothesis (there is no difference), reversing the role of the null and alternate hypotheses, and defining an interval within which groups are said to be equivalent. We then work through an example and show how to calculate sample sizes for noninferiority studies.

Causal null hypotheses of sustained treatment strategies: What can be tested with an instrumental variable?

Science.gov (United States)

Swanson, Sonja A; Labrecque, Jeremy; Hernán, Miguel A

2018-05-02

Sometimes instrumental variable methods are used to test whether a causal effect is null rather than to estimate the magnitude of a causal effect. However, when instrumental variable methods are applied to time-varying exposures, as in many Mendelian randomization studies, it is unclear what causal null hypothesis is tested. Here, we consider different versions of causal null hypotheses for time-varying exposures, show that the instrumental variable conditions alone are insufficient to test some of them, and describe additional assumptions that can be made to test a wider range of causal null hypotheses, including both sharp and average causal null hypotheses. Implications for interpretation and reporting of instrumental variable results are discussed.

Measurement of high-departure aspheres using subaperture stitching with the Variable Optical Null (VON)

Science.gov (United States)

Kulawiec, Andrew; Murphy, Paul; DeMarco, Michael

2010-10-01

Aspheric surfaces are proven to provide significant benefits to a wide variety of optical systems, but the ability to produce high-precision aspheric surfaces has historically been limited by the ability (or lack thereof) to measure them. Traditionally, aspheric measurements have required dedicated null optics, but the cost, lead time, and calibration difficulty of using null optics has made the use of aspheres more challenging and less attractive. In the past three years, QED has developed the Subaperture Stitching Interferometer for Aspheres (SSI-A®) to help address this limitation, providing flexible aspheric measurement capability of up to 200 waves of aspheric departure from best-fit sphere. Some aspheres, however, have thousands of waves of departure. We have recently developed Variable Optical Null (VON) technology that can null much of the aspheric departure in a subaperture. The VON is automatically configurable and is adjusted to nearly null each specific subaperture of an asphere. This ability to nearly null a local subaperture of an asphere provides a significant boost in aspheric measurement capability, enabling aspheres with up to 1000 waves of departure to be measured, without the use of dedicated null optics. We outline the basic principles of subaperture stitching and VON technology, demonstrate the extended capability provided by the VON, and present measurement results from the new Aspheric Stitching Interferometer (ASI®).

Broadband Active Segmented Aperture and Radial Shear Nulling

Data.gov (United States)

National Aeronautics and Space Administration — The Visible Nulling Coronagraph (VNC) is a starlight suppression system for enabling exoplanet detectionand atmospheric measurement. Conceptual space telescope...

Null canonical formalism 1, Maxwell field. [Poisson brackets, boundary conditions

Energy Technology Data Exchange (ETDEWEB)

Wodkiewicz, K [Warsaw Univ. (Poland). Inst. Fizyki Teoretycznej

1975-01-01

The purpose of this paper is to formulate the canonical formalism on null hypersurfaces for the Maxwell electrodynamics. The set of the Poisson brackets relations for null variables of the Maxwell field is obtained. The asymptotic properties of the theory are investigated. The Poisson bracket relations for the news-functions of the Maxwell field are computed. The Hamiltonian form of the asymptotic Maxwell equations in terms of these news-functions is obtained.

Spherical null geodesics of rotating Kerr black holes

International Nuclear Information System (INIS)

Hod, Shahar

2013-01-01

The non-equatorial spherical null geodesics of rotating Kerr black holes are studied analytically. Unlike the extensively studied equatorial circular orbits whose radii are known analytically, no closed-form formula exists in the literature for the radii of generic (non-equatorial) spherical geodesics. We provide here an approximate formula for the radii r ph (a/M;cosi) of these spherical null geodesics, where a/M is the dimensionless angular momentum of the black hole and cos i is an effective inclination angle (with respect to the black-hole equatorial plane) of the orbit. It is well-known that the equatorial circular geodesics of the Kerr spacetime (the prograde and the retrograde orbits with cosi=±1) are characterized by a monotonic dependence of their radii r ph (a/M;cosi=±1) on the dimensionless spin-parameter a/M of the black hole. We use here our novel analytical formula to reveal that this well-known property of the equatorial circular geodesics is actually not a generic property of the Kerr spacetime. In particular, we find that counter-rotating spherical null orbits in the range (3√(3)−√(59))/4≲cosi ph (a/M;cosi=const) on the dimensionless rotation-parameter a/M of the black hole. Furthermore, it is shown that spherical photon orbits of rapidly-rotating black holes are characterized by a critical inclination angle, cosi=√(4/7), above which the coordinate radii of the orbits approach the black-hole radius in the extremal limit. We prove that this critical inclination angle signals a transition in the physical properties of the spherical null geodesics: in particular, it separates orbits which are characterized by finite proper distances to the black-hole horizon from orbits which are characterized by infinite proper distances to the horizon.

A Null Space Control of Two Wheels Driven Mobile Manipulator Using Passivity Theory

Science.gov (United States)

Shibata, Tsuyoshi; Murakami, Toshiyuki

This paper describes a control strategy of null space motion of a two wheels driven mobile manipulator. Recently, robot is utilized in various industrial fields and it is preferable for the robot manipulator to have multiple degrees of freedom motion. Several studies of kinematics for null space motion have been proposed. However stability analysis of null space motion is not enough. Furthermore, these approaches apply to stable systems, but they do not apply unstable systems. Then, in this research, base of manipulator equips with two wheels driven mobile robot. This robot is called two wheels driven mobile manipulator, which becomes unstable system. In the proposed approach, a control design of null space uses passivity based stabilizing. A proposed controller is decided so that closed-loop system of robot dynamics satisfies passivity. This is passivity based control. Then, control strategy is that stabilizing of the robot system applies to work space observer based approach and null space control while keeping end-effector position. The validity of the proposed approach is verified by simulations and experiments of two wheels driven mobile manipulator.

Standard and Null Weak Values

OpenAIRE

Zilberberg, Oded; Romito, Alessandro; Gefen, Yuval

2013-01-01

Weak value (WV) is a quantum mechanical measurement protocol, proposed by Aharonov, Albert, and Vaidman. It consists of a weak measurement, which is weighed in, conditional on the outcome of a later, strong measurement. Here we define another two-step measurement protocol, null weak value (NVW), and point out its advantages as compared to WV. We present two alternative derivations of NWVs and compare them to the corresponding derivations of WVs.

Anti-optic-null medium: Achieving the optic-null medium effect by enclosing an air region with relatively low-anisotropy media

Science.gov (United States)

Sun, Fei; Liu, Yichao; He, Sailing

2016-07-01

A so-called anti-optic-null medium (anti-ONM), which can be utilized to cancel the optic-null medium (ONM) and create many novel optical illusions, is introduced and designed by transformation optics (TO). Optical separation illusions can be achieved with an anti-ONM. With the help of the anti-ONM, we can achieve the same optical illusions where ONM is required via a shelled structure filled with low anisotropic medium, which is easier to realize for some novel optical devices designed by TO and optical surface transformation. The special function of the anti-ONM will lead to a new way to design optical devices or simplify the material requirements. Overlapping illusions, and wave-front reshapers are designed to demonstrate the function of the proposed method.

Instabilities and the null energy condition

International Nuclear Information System (INIS)

Buniy, Roman V.; Hsu, Stephen D.H.

2006-01-01

We show that violation of the null energy condition implies instability in a broad class of models, including gauge theories with scalar and fermionic matter as well as any perfect fluid. When applied to the dark energy, our results imply that w=p/ρ is unlikely to be less than -1. than -1

OBSERVATION OF MAGNETIC RECONNECTION AT A 3D NULL POINT ASSOCIATED WITH A SOLAR ERUPTION

International Nuclear Information System (INIS)

Sun, J. Q.; Yang, K.; Cheng, X.; Ding, M. D.; Zhang, J.

2016-01-01

Magnetic null has long been recognized as a special structure serving as a preferential site for magnetic reconnection (MR). However, the direct observational study of MR at null-points is largely lacking. Here, we show the observations of MR around a magnetic null associated with an eruption that resulted in an M1.7 flare and a coronal mass ejection. The Geostationary Operational Environmental Satellites X-ray profile of the flare exhibited two peaks at ∼02:23 UT and ∼02:40 UT on 2012 November 8, respectively. Based on the imaging observations, we find that the first and also primary X-ray peak was originated from MR in the current sheet (CS) underneath the erupting magnetic flux rope (MFR). On the other hand, the second and also weaker X-ray peak was caused by MR around a null point located above the pre-eruption MFR. The interaction of the null point and the erupting MFR can be described as a two-step process. During the first step, the erupting and fast expanding MFR passed through the null point, resulting in a significant displacement of the magnetic field surrounding the null. During the second step, the displaced magnetic field started to move back, resulting in a converging inflow and subsequently the MR around the null. The null-point reconnection is a different process from the current sheet reconnection in this flare; the latter is the cause of the main peak of the flare, while the former is the cause of the secondary peak of the flare and the conspicuous high-lying cusp structure.

Parallel-propagated frame along null geodesics in higher-dimensional black hole spacetimes

International Nuclear Information System (INIS)

Kubiznak, David; Frolov, Valeri P.; Connell, Patrick; Krtous, Pavel

2009-01-01

In [arXiv:0803.3259] the equations describing the parallel transport of orthonormal frames along timelike (spacelike) geodesics in a spacetime admitting a nondegenerate principal conformal Killing-Yano 2-form h were solved. The construction employed is based on studying the Darboux subspaces of the 2-form F obtained as a projection of h along the geodesic trajectory. In this paper we demonstrate that, although slightly modified, a similar construction is possible also in the case of null geodesics. In particular, we explicitly construct the parallel-transported frames along null geodesics in D=4, 5, 6 Kerr-NUT-(A)dS spacetimes. We further discuss the parallel transport along principal null directions in these spacetimes. Such directions coincide with the eigenvectors of the principal conformal Killing-Yano tensor. Finally, we show how to obtain a parallel-transported frame along null geodesics in the background of the 4D Plebanski-Demianski metric which admits only a conformal generalization of the Killing-Yano tensor.

On the geometry of null cones to infinity under curvature flux bounds

International Nuclear Information System (INIS)

Alexakis, Spyros; Shao, Arick

2014-01-01

The main objective of this paper is to control the geometry of a future outgoing truncated null cone extending smoothly toward infinity in an Einstein-vacuum spacetime. In particular, we wish to do this under minimal regularity assumptions, namely, at the (weighted) L 2 -curvature level. We show that if the curvature flux and the data on an initial sphere of the cone are sufficiently close to the corresponding values in a standard Minkowski or Schwarzschild null cone, then we can obtain quantitative bounds on the geometry of the entire infinite cone. The same bounds also imply the existence of limits at infinity, along the null cone, of naturally scaled geometric quantities. In Alexakis and Shao (2013 Bounds on the Bondi energy by a flux of curvature arXiv:1308.4170), we will apply these results in order to control various physical quantities—e.g., the Bondi energy and (linear and angular) momenta—associated with such infinite null cones in vacuum spacetimes. (paper)

Simple Fourier optics formalism for high-angular-resolution systems and nulling interferometry.

Science.gov (United States)

Hénault, François

2010-03-01

Reviewed are various designs of advanced, multiaperture optical systems dedicated to high-angular-resolution imaging or to the detection of exoplanets by nulling interferometry. A simple Fourier optics formalism applicable to both imaging arrays and nulling interferometers is presented, allowing their basic theoretical relationships to be derived as convolution or cross-correlation products suitable for fast and accurate computation. Several unusual designs, such as a "superresolving telescope" utilizing a mosaicking observation procedure or a free-flying, axially recombined interferometer are examined, and their performance in terms of imaging and nulling capacity are assessed. In all considered cases, it is found that the limiting parameter is the diameter of the individual telescopes. A final section devoted to nulling interferometry shows an apparent superiority of axial versus multiaxial recombining schemes. The entire study is valid only in the framework of first-order geometrical optics and scalar diffraction theory. Furthermore, it is assumed that all entrance subapertures are optically conjugated with their associated exit pupils.

Abnormal Activation of BMP Signaling Causes Myopathy in Fbn2 Null Mice.

Directory of Open Access Journals (Sweden)

Gerhard Sengle

2015-06-01

Full Text Available Fibrillins are large extracellular macromolecules that polymerize to form the backbone structure of connective tissue microfibrils. Mutations in the gene for fibrillin-1 cause the Marfan syndrome, while mutations in the gene for fibrillin-2 cause Congenital Contractural Arachnodactyly. Both are autosomal dominant disorders, and both disorders affect musculoskeletal tissues. Here we show that Fbn2 null mice (on a 129/Sv background are born with reduced muscle mass, abnormal muscle histology, and signs of activated BMP signaling in skeletal muscle. A delay in Myosin Heavy Chain 8, a perinatal myosin, was found in Fbn2 null forelimb muscle tissue, consistent with the notion that muscle defects underlie forelimb contractures in these mice. In addition, white fat accumulated in the forelimbs during the early postnatal period. Adult Fbn2 null mice are already known to demonstrate persistent muscle weakness. Here we measured elevated creatine kinase levels in adult Fbn2 null mice, indicating ongoing cycles of muscle injury. On a C57Bl/6 background, Fbn2 null mice showed severe defects in musculature, leading to neonatal death from respiratory failure. These new findings demonstrate that loss of fibrillin-2 results in phenotypes similar to those found in congenital muscular dystrophies and that FBN2 should be considered as a candidate gene for recessive congenital muscular dystrophy. Both in vivo and in vitro evidence associated muscle abnormalities and accumulation of white fat in Fbn2 null mice with abnormally activated BMP signaling. Genetic rescue of reduced muscle mass and accumulation of white fat in Fbn2 null mice was accomplished by deleting a single allele of Bmp7. In contrast to other reports that activated BMP signaling leads to muscle hypertrophy, our findings demonstrate the exquisite sensitivity of BMP signaling to the fibrillin-2 extracellular environment during early postnatal muscle development. New evidence presented here suggests that

Purification and functional characterization of nine human Aquaporins produced in Saccharomyces cerevisiae for the purpose of biophysical characterization

DEFF Research Database (Denmark)

Pedersen, Per Amstrup; Gourdon, Pontus Emanuel; Gotfryd, Kamil

2017-01-01

investigated the capacity of S. cerevisiae to deliver high yields of prime quality human AQPs, focusing on poorly characterized members including some previously shown to be difficult to isolate. Exploiting GFP labeled forms we comprehensively optimized production and purification procedures resulting...... in satisfactory yields of all nine AQP targets. We applied the obtained knowledge to successfully upscale purification of histidine tagged human AQP10 produced in large bioreactors. Glycosylation analysis revealed that AQP7 and 12 were O-glycosylated, AQP10 was N-glycosylated while the other AQPs were...... not glycosylated. We furthermore performed functional characterization and found that AQP 2, 6 and 8 allowed flux of water whereas AQP3, 7, 9, 10, 11 and 12 also facilitated a glycerol flux. In conclusion, our S. cerevisiae platform emerges as a powerful tool for isolation of functional, difficult-to-express human...

Pattern Nulling of Linear Antenna Arrays Using Backtracking Search Optimization Algorithm

Directory of Open Access Journals (Sweden)

Kerim Guney

2015-01-01

Full Text Available An evolutionary method based on backtracking search optimization algorithm (BSA is proposed for linear antenna array pattern synthesis with prescribed nulls at interference directions. Pattern nulling is obtained by controlling only the amplitude, position, and phase of the antenna array elements. BSA is an innovative metaheuristic technique based on an iterative process. Various numerical examples of linear array patterns with the prescribed single, multiple, and wide nulls are given to illustrate the performance and flexibility of BSA. The results obtained by BSA are compared with the results of the following seventeen algorithms: particle swarm optimization (PSO, genetic algorithm (GA, modified touring ant colony algorithm (MTACO, quadratic programming method (QPM, bacterial foraging algorithm (BFA, bees algorithm (BA, clonal selection algorithm (CLONALG, plant growth simulation algorithm (PGSA, tabu search algorithm (TSA, memetic algorithm (MA, nondominated sorting GA-2 (NSGA-2, multiobjective differential evolution (MODE, decomposition with differential evolution (MOEA/D-DE, comprehensive learning PSO (CLPSO, harmony search algorithm (HSA, seeker optimization algorithm (SOA, and mean variance mapping optimization (MVMO. The simulation results show that the linear antenna array synthesis using BSA provides low side-lobe levels and deep null levels.

Partial null astigmatism-compensated interferometry for a concave freeform Zernike mirror

Science.gov (United States)

Dou, Yimeng; Yuan, Qun; Gao, Zhishan; Yin, Huimin; Chen, Lu; Yao, Yanxia; Cheng, Jinlong

2018-06-01

Partial null interferometry without using any null optics is proposed to measure a concave freeform Zernike mirror. Oblique incidence on the freeform mirror is used to compensate for astigmatism as the main component in its figure, and to constrain the divergence of the test beam as well. The phase demodulated from the partial nulled interferograms is divided into low-frequency phase and high-frequency phase by Zernike polynomial fitting. The low-frequency surface figure error of the freeform mirror represented by the coefficients of Zernike polynomials is reconstructed from the low-frequency phase, applying the reverse optimization reconstruction technology in the accurate model of the interferometric system. The high-frequency surface figure error of the freeform mirror is retrieved from the high-frequency phase adopting back propagating technology, according to the updated model in which the low-frequency surface figure error has been superimposed on the sag of the freeform mirror. Simulations verified that this method is capable of testing a wide variety of astigmatism-dominated freeform mirrors due to the high dynamic range. The experimental result using our proposed method for a concave freeform Zernike mirror is consistent with the null test result employing the computer-generated hologram.

Red hair is the null phenotype of MC1R.

Science.gov (United States)

Beaumont, Kimberley A; Shekar, Sri N; Cook, Anthony L; Duffy, David L; Sturm, Richard A

2008-08-01

The Melanocortin-1 Receptor (MC1R) is a G-protein coupled receptor, which is responsible for production of the darker eumelanin pigment and the tanning response. The MC1R gene has many polymorphisms, some of which have been linked to variation in pigmentation phenotypes within human populations. In particular, the p.D84E, p.R151C, p.R160W and p.D294 H alleles have been strongly associated with red hair, fair skin and increased skin cancer risk. These red hair colour (RHC) variants are relatively well described and are thought to result in altered receptor function, while still retaining varying levels of signaling ability in vitro. The mouse Mc1r null phenotype is yellow fur colour, the p.R151C, p.R160W and p.D294 H alleles were able to partially rescue this phenotype, leading to the question of what the true null phenotype of MC1R would be in humans. Due to the rarity of MC1R null alleles in human populations, they have only been found in the heterozygous state until now. We report here the first case of a homozygous MC1R null individual, phenotypic analysis indicates that red hair and fair skin is found in the absence of MC1R function.

Apoptosis in spermatogonia irradiated P53 null mice

International Nuclear Information System (INIS)

Streit-Bianchi, M.; Hendry, J.H.; Roberts, S.A.; Morris, J.D.; Durgaryan, A.A.

2007-01-01

Complete text of publication follows. The exposure of germ cells to ionizing radiations is of concern both from high-dose therapeutic exposures and from low doses causing deleterious trans-generational mutations. P53 protein plays an important role in cellular damage and is expressed in the testis normally during meiosis, its expression being localised to the preleptotene and early/mid pachytene spermatocytes. P53 null mice, heterozygotes possessing a 129 Sv/C57BL6 genetic background and B6D2F1 mice have been irradiated to 1 and 2 Gy single doses. Fractionated exposures of 1+1 Gy at 4 hours interval were also carried out. Apoptosis induction, spermatogonia and spermatocytes survival were assessed by microscope analysis of histological samples at 4 to 96 hours after irradiation in time-course experiments. The same end-points were also assessed at 72 and 96 hours after irradiation to single doses in the region between 20cGy to 2Gy. A dose dependent level of p53 expression was observed at 4 hours after irradiation to 1 and 2 Gy which returned to normal level by 24 hours. Our data support a two process mode of apoptosis with a first wave around 12 hours followed by a second wave at 2-3 days. The first wave apoptosis is substantially reduced in p53 null mice whereas the second wave is reduced in B6D2F1 mice. The initial increase in apoptosis was delayed in some stages of the of germ cells development which were identified by the spermatids shape. Clear correlation exists between apoptosis and survival assessed in stage XI-XII Tubules 72 hours after irradiation. The data are in agreement with other data in literature indicating that irradiated spermatogonia die through apoptosis. The lack of apoptosis observed in p53 null mice results in a very high survival rate of daughter cells assessed later. Theses spermatocytes and the following progenitor cells are likely to carry mutations as most will not die in the smaller second wave of apoptosis observed 3 days after

Vortical null orbits, repulsive barriers, energy confinement in Kerr metric

Energy Technology Data Exchange (ETDEWEB)

Calvani, M [Padua Univ. (Italy). Ist. di Astronomia; De Felice, F

1978-10-01

The complete analytical description of the null trajectories in the field of a Kerr naked singularity is given. Two peculiar phenomena are described: the existence of repulsive barriers in the r < O world and the existence of null circular bound orbits which surround the singularity in 'shells'. They distribute around the surface at r = m, which is the position of the horizon in the extreme black-hole case; this suggests that a naked singularity 'remembers' the position of the last horizon.

Future null infinity of Robertson-Walker spacetimes

International Nuclear Information System (INIS)

Moreschi, O.M.

1988-08-01

The future null infinity for all non-contracting Robertson-Walker space time is studied systematically. A theorem is proved which establishes the expected relation between the nature of J + and the appearance or absence of cosmic event horizons. (author). 7 refs, 1 tab

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) produces edema due to BBB disruption induced by MMP-9 activation in rat hippocampus.

Science.gov (United States)

Pérez-Hernández, Mercedes; Fernández-Valle, María Encarnación; Rubio-Araiz, Ana; Vidal, Rebeca; Gutiérrez-López, María Dolores; O'Shea, Esther; Colado, María Isabel

2017-05-15

The recreational drug of abuse, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier (BBB) integrity in rats through an early P2X 7 receptor-mediated event which induces MMP-9 activity. Increased BBB permeability often causes plasma proteins and water to access cerebral tissue leading to vasogenic edema formation. The current study was performed to examine the effect of a single neurotoxic dose of MDMA (12.5 mg/kg, i.p.) on in vivo edema development associated with changes in the expression of the perivascular astrocytic water channel, AQP4, as well as in the expression of the tight-junction (TJ) protein, claudin-5 and Evans Blue dye extravasation in the hippocampus of adult male Dark Agouti rats. We also evaluated the ability of the MMP-9 inhibitor, SB-3CT (25 mg/kg, i.p.), to prevent these changes in order to validate the involvement of MMP-9 activation in MDMA-induced BBB disruption. The results show that MDMA produces edema of short duration temporally associated with changes in AQP4 expression and a reduction in claudin-5 expression, changes which are prevented by SB-3CT. In addition, MDMA induces a short-term increase in both tPA activity and expression, a serine-protease which is involved in BBB disruption and upregulation of MMP-9 expression. In conclusion, this study provides evidence enough to conclude that MDMA induces edema of short duration due to BBB disruption mediated by MMP-9 activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of choice of null network on small-world parameters of structural correlation networks.

Directory of Open Access Journals (Sweden)

S M Hadi Hosseini

Full Text Available In recent years, coordinated variations in brain morphology (e.g., volume, thickness have been employed as a measure of structural association between brain regions to infer large-scale structural correlation networks. Recent evidence suggests that brain networks constructed in this manner are inherently more clustered than random networks of the same size and degree. Thus, null networks constructed by randomizing topology are not a good choice for benchmarking small-world parameters of these networks. In the present report, we investigated the influence of choice of null networks on small-world parameters of gray matter correlation networks in healthy individuals and survivors of acute lymphoblastic leukemia. Three types of null networks were studied: 1 networks constructed by topology randomization (TOP, 2 networks matched to the distributional properties of the observed covariance matrix (HQS, and 3 networks generated from correlation of randomized input data (COR. The results revealed that the choice of null network not only influences the estimated small-world parameters, it also influences the results of between-group differences in small-world parameters. In addition, at higher network densities, the choice of null network influences the direction of group differences in network measures. Our data suggest that the choice of null network is quite crucial for interpretation of group differences in small-world parameters of structural correlation networks. We argue that none of the available null models is perfect for estimation of small-world parameters for correlation networks and the relative strengths and weaknesses of the selected model should be carefully considered with respect to obtained network measures.

Influence of Choice of Null Network on Small-World Parameters of Structural Correlation Networks

Science.gov (United States)

Hosseini, S. M. Hadi; Kesler, Shelli R.

2013-01-01

In recent years, coordinated variations in brain morphology (e.g., volume, thickness) have been employed as a measure of structural association between brain regions to infer large-scale structural correlation networks. Recent evidence suggests that brain networks constructed in this manner are inherently more clustered than random networks of the same size and degree. Thus, null networks constructed by randomizing topology are not a good choice for benchmarking small-world parameters of these networks. In the present report, we investigated the influence of choice of null networks on small-world parameters of gray matter correlation networks in healthy individuals and survivors of acute lymphoblastic leukemia. Three types of null networks were studied: 1) networks constructed by topology randomization (TOP), 2) networks matched to the distributional properties of the observed covariance matrix (HQS), and 3) networks generated from correlation of randomized input data (COR). The results revealed that the choice of null network not only influences the estimated small-world parameters, it also influences the results of between-group differences in small-world parameters. In addition, at higher network densities, the choice of null network influences the direction of group differences in network measures. Our data suggest that the choice of null network is quite crucial for interpretation of group differences in small-world parameters of structural correlation networks. We argue that none of the available null models is perfect for estimation of small-world parameters for correlation networks and the relative strengths and weaknesses of the selected model should be carefully considered with respect to obtained network measures. PMID:23840672

On Bäcklund transformation and vortex filament equation for null Cartan curve in Minkowski 3-space

Energy Technology Data Exchange (ETDEWEB)

Grbović, Milica, E-mail: milica.grbovic@kg.ac.rs; Nešović, Emilija, E-mail: nesovickg@sbb.rs [University of Kragujevac, Faculty of Science, Department of Mathematics and Informatics (Serbia)

2016-12-15

In this paper we introduce Bäcklund transformation of a null Cartan curve in Minkowski 3-space as a transformation which maps a null Cartan helix to another null Cartan helix, congruent to the given one. We also give the sufficient conditions for a transformation between two null Cartan curves in the Minkowski 3-space such that these curves have equal constant torsions. By using the Da Rios vortex filament equation, based on localized induction approximation, we derive the vortex filament equation for a null Cartan curve and obtain evolution equation for it’s torsion. As an application, we show that Cartan’s frame vectors generate new solutions of the Da Rios vortex filament equation.

Left cardiac isomerism in the Sonic hedgehog null mouse.

Science.gov (United States)

Hildreth, Victoria; Webb, Sandra; Chaudhry, Bill; Peat, Jonathan D; Phillips, Helen M; Brown, Nigel; Anderson, Robert H; Henderson, Deborah J

2009-06-01

Sonic hedgehog (Shh) is a secreted morphogen necessary for the production of sidedness in the developing embryo. In this study, we describe the morphology of the atrial chambers and atrioventricular junctions of the Shh null mouse heart. We demonstrate that the essential phenotypic feature is isomerism of the left atrial appendages, in combination with an atrioventricular septal defect and a common atrioventricular junction. These malformations are known to be frequent in humans with left isomerism. To confirm the presence of left isomerism, we show that Pitx2c, a recognized determinant of morphological leftness, is expressed in the Shh null mutants on both the right and left sides of the inflow region, and on both sides of the solitary arterial trunk exiting from the heart. It has been established that derivatives of the second heart field expressing Isl1 are asymmetrically distributed in the developing normal heart. We now show that this population is reduced in the hearts from the Shh null mutants, likely contributing to the defects. To distinguish the consequences of reduced contributions from the second heart field from those of left-right patterning disturbance, we disrupted the movement of second heart field cells into the heart by expressing dominant-negative Rho kinase in the population of cells expressing Isl1. This resulted in absence of the vestibular spine, and presence of atrioventricular septal defects closely resembling those seen in the hearts from the Shh null mutants. The primary atrial septum, however, was well formed, and there was no evidence of isomerism of the atrial appendages, suggesting that these features do not relate to disruption of the contributions made by the second heart field. We demonstrate, therefore, that the Shh null mouse is a model of isomerism of the left atrial appendages, and show that the recognized associated malformations found at the venous pole of the heart in the setting of left isomerism are likely to arise from

[Mechanism of potassium channel in hypoxia-ischemic brain edema: experiment with neonatal rat astrocyte].

Science.gov (United States)

Fu, Xue-mei; Xiang, Long; Liao, Da-qing; Feng, Zhi-chun; Mu, De-zhi

2008-11-04

To investigate the mechanism of potassium channel in brain edema caused by hypoxia-ischemia (HI). Astrocytes were obtained from 3-day-old SD rats, cultured, and randomly divided into 2 groups: normoxia group, cultured under normoxic condition, and hypoxic-ischemic group, cultured under hypoxic-ischemic condition. The cell volume was measured by radiologic method. Patch-clamp technique was used to observe the electric physiological properties of the voltage-gated potassium channels (Kv) in a whole cell configuration, and the change of voltage-gated potassium channel current (IKv) was recorded in cultured neonatal rat astrocyte during HI. Aquaporin 4 (AQP4) expression vector was constructed from pSUPER vector and transfected into the astrocytes (AQP4 RNAi) to construct AQP4 knockdown (AQP4-/-) cells. cellular volume was determined using [3H]-3-O-methyl-D-glucose uptake in both AQP4-/- and AQP4+/+ cells under the condition of HI. Real time PCR and Western blotting were used to detect the mRNA and protein expression of AQP4. The percentages of the AQP4+/+ and AQP4-/- astrocyte volumes in the condition of HI for 0.5, 1, 2, and 4 h were 104+/-7, 109+/-6, 126+/-12, and 152+/-9 times, and 97+/-7, 105+/-9, 109+/-7, and 132+/-6 times as those of their corresponding control groups (all Pastrocytes significantly increased during HI and the degrees of edema mediated by AQP4 knockdown at different time points were all significantly milder (all Pastrocytes via aquaporin-4 and then cell swelling.

Kastor-Traschen black holes, null geodesics and conformal circles

International Nuclear Information System (INIS)

Casey, Stephen

2012-01-01

The Kastor-Traschen metric is a time-dependent solution of the Einstein-Maxwell equations with positive cosmological constant Λ which can be used to describe an arbitrary number of charged dynamical black holes. In this paper, we consider the null geodesic structure of this solution, in particular, focusing on the projection to the space of orbits of the timelike conformal retraction. It is found that these projected light rays arise as integral curves of a system of third-order ordinary differential equations. This system is not uniquely defined, however, and we use the inherent freedom to construct a new system whose integral curves coincide with the projection of distinguished null curves of Kastor-Traschen arising from a magnetic flow. We discuss our results in the one-centre case and demonstrate a link to conformal circles in the limit Λ → 0. We also show how to construct analytic expressions for the projected null geodesics of this metric by exploiting a well-known diffeomorphism between the K-T metric and extremal Reissner-Nordstrom-de Sitter. We make some remarks about the two-centre solution and demonstrate a link with the one-centre case. (paper)

The quantum null energy condition in curved space

Science.gov (United States)

Fu, Zicao; Koeller, Jason; Marolf, Donald

2017-11-01

The quantum null energy condition (QNEC) is a conjectured bound on components (Tkk = Tab ka k^b) of the stress tensor along a null vector k a at a point p in terms of a second k-derivative of the von Neumann entropy S on one side of a null congruence N through p generated by k a . The conjecture has been established for super-renormalizeable field theories at points p that lie on a bifurcate Killing horizon with null tangent k a and for large-N holographic theories on flat space. While the Koeller-Leichenauer holographic argument clearly yields an inequality for general ( p, k^a) , more conditions are generally required for this inequality to be a useful QNEC. For d≤slant 3 , for arbitrary backgroud metric we show that the QNEC is naturally finite and independent of renormalization scheme when the expansion θ of N at the point p vanishes. This is consistent with the original QNEC conjecture which required θ and the shear σab to satisfy θ \\vert _p= \\dotθ\\vert p =0 , σab\\vert _p=0 . But for d=4, 5 more conditions than even these are required. In particular, we also require the vanishing of additional derivatives and a dominant energy condition. In the above cases the holographic argument does indeed yield a finite QNEC, though for d≥slant6 we argue these properties to fail even for weakly isolated horizons (where all derivatives of θ, σab vanish) that also satisfy a dominant energy condition. On the positive side, a corrollary to our work is that, when coupled to Einstein-Hilbert gravity, d ≤slant 3 holographic theories at large N satisfy the generalized second law (GSL) of thermodynamics at leading order in Newton’s constant G. This is the first GSL proof which does not require the quantum fields to be perturbations to a Killing horizon.

Noncolocated Time-Reversal MUSIC: High-SNR Distribution of Null Spectrum

Science.gov (United States)

Ciuonzo, Domenico; Rossi, Pierluigi Salvo

2017-04-01

We derive the asymptotic distribution of the null spectrum of the well-known Multiple Signal Classification (MUSIC) in its computational Time-Reversal (TR) form. The result pertains to a single-frequency non-colocated multistatic scenario and several TR-MUSIC variants are here investigated. The analysis builds upon the 1st-order perturbation of the singular value decomposition and allows a simple characterization of null-spectrum moments (up to the 2nd order). This enables a comparison in terms of spectrums stability. Finally, a numerical analysis is provided to confirm the theoretical findings.

Hypersensitivities for acetaldehyde and other agents among cancer cells null for clinically relevant Fanconi anemia genes.

Science.gov (United States)

Ghosh, Soma; Sur, Surojit; Yerram, Sashidhar R; Rago, Carlo; Bhunia, Anil K; Hossain, M Zulfiquer; Paun, Bogdan C; Ren, Yunzhao R; Iacobuzio-Donahue, Christine A; Azad, Nilofer A; Kern, Scott E

2014-01-01

Large-magnitude numerical distinctions (>10-fold) among drug responses of genetically contrasting cancers were crucial for guiding the development of some targeted therapies. Similar strategies brought epidemiological clues and prevention goals for genetic diseases. Such numerical guides, however, were incomplete or low magnitude for Fanconi anemia pathway (FANC) gene mutations relevant to cancer in FANC-mutation carriers (heterozygotes). We generated a four-gene FANC-null cancer panel, including the engineering of new PALB2/FANCN-null cancer cells by homologous recombination. A characteristic matching of FANCC-null, FANCG-null, BRCA2/FANCD1-null, and PALB2/FANCN-null phenotypes was confirmed by uniform tumor regression on single-dose cross-linker therapy in mice and by shared chemical hypersensitivities to various inter-strand cross-linking agents and γ-radiation in vitro. Some compounds, however, had contrasting magnitudes of sensitivity; a strikingly high (19- to 22-fold) hypersensitivity was seen among PALB2-null and BRCA2-null cells for the ethanol metabolite, acetaldehyde, associated with widespread chromosomal breakage at a concentration not producing breaks in parental cells. Because FANC-defective cancer cells can share or differ in their chemical sensitivities, patterns of selective hypersensitivity hold implications for the evolutionary understanding of this pathway. Clinical decisions for cancer-relevant prevention and management of FANC-mutation carriers could be modified by expanded studies of high-magnitude sensitivities. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Dall-Null tester for spaceborne applications

Science.gov (United States)

Wingler, R. L.

1984-12-01

This is a study to design a self correcting primary mirror system for a space telescope. The design is centered around a Dall-Null tester (a Foucault knife-edge tester with compensating lens). An indepth study of the theory of the Foucault test from Foucault's original publications to current work is presented. Also short comings of the diffraction approach are shown. The findings of a simple experiment showed the way to the correct explanation as to the workings of the test. Based on this new explanation, a computer program to find the error in the surface of the mirror from the irradiance pattern provided by the Dall-Null tester was developed. The computer program with a sample run is included in the appendixes A and B. The basic design of an adaptive optic system for a spaceborne application is also presented in the paper. This design has the desired quality of being able to correct the mirror while the telescope is in use. The equations being independent of wavelength allows for the design to be applied to systems working outside of the visible spectrum as well as the systems working in the visible.

Averaged null energy condition from causality

Science.gov (United States)

Hartman, Thomas; Kundu, Sandipan; Tajdini, Amirhossein

2017-07-01

Unitary, Lorentz-invariant quantum field theories in flat spacetime obey mi-crocausality: commutators vanish at spacelike separation. For interacting theories in more than two dimensions, we show that this implies that the averaged null energy, ∫ duT uu , must be non-negative. This non-local operator appears in the operator product expansion of local operators in the lightcone limit, and therefore contributes to n-point functions. We derive a sum rule that isolates this contribution and is manifestly positive. The argument also applies to certain higher spin operators other than the stress tensor, generating an infinite family of new constraints of the form ∫ duX uuu··· u ≥ 0. These lead to new inequalities for the coupling constants of spinning operators in conformal field theory, which include as special cases (but are generally stronger than) the existing constraints from the lightcone bootstrap, deep inelastic scattering, conformal collider methods, and relative entropy. We also comment on the relation to the recent derivation of the averaged null energy condition from relative entropy, and suggest a more general connection between causality and information-theoretic inequalities in QFT.

CHIP regulates aquaporin-2 quality control and body water homeostasis

DEFF Research Database (Denmark)

Wu, Qi; Moeller, Hanne B.; Stevens, Donté A.

2018-01-01

The importance of the kidney distal convoluted tubule (DCT) and cortical collecting duct (CCD) is highlighted by various water and electrolyte disorders that arise when the unique transport properties of these segments are disturbed. Despite this critical role, little is known about which proteins...... by vasopressin; interacts with aquaporin-2 (AQP2), Hsp70, and Hsc70; and can directly ubiquitylate the water channel AQP2 in vitro. shRNA knockdown of CHIP in CCD cells increased AQP2 protein t1/2 and reduced AQP2 ubiquitylation, resulting in greater levels of AQP2 andphosphorylatedAQP2.CHIP knockdown increased...... the plasma membrane abundance of AQP2 in these cells. Compared with wild-type controls, CHIP knockout mice or novel CRISPR/Cas9 mice without CHIPE3 ligase activity had greater AQP2 abundance and altered renal water handling, with decreased water intake and urine volume, alongside higher urine osmolality. We...

Null-point titration measurements of free magnesium in stored erythrocytes

International Nuclear Information System (INIS)

Bock, J.L.; Yusuf, Y.; Puntillo, E.

1987-01-01

Free intracellular magnesium concentration (Mg/sub i/) was measured in stored human erythrocytes, using null-point titration with ionophore A23187. For cells stored 31 P NMR spectroscopy, which showed a decrease in Mg/sub i/ with storage. However, the NMR measurements are performed with no pretreatment of the cells, while the null-point method requires an initial washing step, which alters pH/sub i/ and may also alter Mg/sub i/. The titration-measured Mg/sub i/ values are still surprisingly low for long-stored cells, considering that depletion of ATP and 2,3-DPG should release bound Mg. Using the titration-measured Mg/sub i/ values along with measurements of total Mg, ATP, and 2,3-DPG, they estimate that an additional buffer contains about 47% of total Mg in cells stored 21 days. Mg/sub i/ determinations by both 31 P NMR and null-point titration thus indicate that erythrocyte Mg is largely bound to a high-capacity, low-affinity buffer whose relative importance increases during cell storage. Discrepancies between the methods require further investigation

PERSEE: a nulling interferometer with dynamic correction of external perturbations

Science.gov (United States)

Jacquinod, S.; Houairi, K.; Le Duigou, J.-M.; Barillot, M.; Cassaing, F.; Réess, J.-M.; Hénault, F.; Sorrente, B.; Morinaud, G.; Amans, J.-P.; Coudé du Foresto, V.; Ollivier, M.

2017-11-01

Nulling interferometry is one of the direct detection methods assessed to find and characterize extrasolar planets and particularly telluric ones. Several projects such as Darwin [1;2], TPF-I [3;4], PEGASE [5;6] or FKSI [7], are currently considered. One of the main issues is the feasibility of a stable polychromatic null despite the presence of significant disturbances, induced by vibrations, atmospheric turbulence on the ground or satellite drift. Satisfying all these requirements is a great challenge and a key issue of these missions. In the context of the PEGASE mission, it was decided (in 2006), to build a laboratory demonstrator named PERSEE. It is the first laboratory setup which couples deep nulling interferometry with a free flying GNC simulator [8]. It is developed by a consortium composed of CNES, IAS, LESIA, OCA, ONERA, and TAS. In this paper, we detail the main objectives, the set-up and the function of the bench. We describe all the subsystems and we focus particularly on two key points of PERSEE: the beam combiner and the Fringe tracker.

Reversing hypomyelination in BACE1-null mice with Akt-DD overexpression.

Science.gov (United States)

Hu, Xiangyou; Schlanger, Rita; He, Wanxia; Macklin, Wendy B; Yan, Riqiang

2013-05-01

β-Site amyloid precursor protein convertase enzyme 1 (BACE1), a type I transmembrane aspartyl protease required to cleave amyloid precursor protein for releasing a toxic amyloid peptide, also cleaves type I and type III neuregulin-1 (Nrg-1). BACE1 deficiency in mice causes hypomyelination during development and impairs remyelination if injured. In BACE1-null mice, the abolished cleavage of neuregulin-1 by BACE1 is speculated to cause reduced myelin sheath thickness in both the central nervous system and peripheral nervous system because reduced cleavage of Nrg-1 correlates with reduced Akt phosphorylation, a downstream signaling molecule of the Nrg-1/ErbB pathway. Here we tested specifically whether increasing Akt activity alone in oligodendrocytes would be sufficient to reverse the hypomyelination phenotype in BACE1-null mice. BACE1-null mice were bred with transgenic mice expressing constitutively active Akt (Akt-DD; mutations with D(308)T and D(473)S) in oligodendrocytes. Relative to littermate BACE1-null controls, BACE1(-/-)/Akt-DD mice exhibited enhanced expression of myelin basic protein and promoter of proteolipid protein. The elevated expression of myelin proteins correlated with a thicker myelin sheath in optic nerves; comparison of quantified g ratios with statistic significance was used to confirm this reversion. However, it appeared that myelin sheath thickness in the sciatic nerves was not increased in BACE1(-/-)/Akt-DD mice, as the g ratio was not significantly different from the control. Hence, increased Akt activity in BACE1-null myelinating cells only compensates for the loss of BACE1 activity in the central nervous system, which is consistent with the observation that overexpression of Akt-DD in Schwann cells did not induce hypermyelination. Our results suggest that signaling activity other than Akt may also contribute to proper myelination in peripheral nerves.

The Quantum Focussing Conjecture and Quantum Null Energy Condition

Science.gov (United States)

Koeller, Jason

Evidence has been gathering over the decades that spacetime and gravity are best understood as emergent phenomenon, especially in the context of a unified description of quantum mechanics and gravity. The Quantum Focussing Conjecture (QFC) and Quantum Null Energy Condition (QNEC) are two recently-proposed relationships between entropy and geometry, and energy and entropy, respectively, which further strengthen this idea. In this thesis, we study the QFC and the QNEC. We prove the QNEC in a variety of contexts, including free field theories on Killing horizons, holographic theories on Killing horizons, and in more general curved spacetimes. We also consider the implications of the QFC and QNEC in asymptotically flat space, where they constrain the information content of gravitational radiation arriving at null infinity, and in AdS/CFT, where they are related to other semiclassical inequalities and properties of boundary-anchored extremal area surfaces. It is shown that the assumption of validity and vacuum-state saturation of the QNEC for regions of flat space defined by smooth cuts of null planes implies a local formula for the modular Hamiltonian of these regions. We also demonstrate that the QFC as originally conjectured can be violated in generic theories in d ≥ 5, which led the way to an improved formulation subsequently suggested by Stefan Leichenauer.

Zero emission city. Preliminary study; Null-Emissions-Stadt. Sondierungsstudie

Energy Technology Data Exchange (ETDEWEB)

Diefenbach, N; Enseling, A; Werner, P; Flade, A; Greiff, R; Hennings, D; Muehlich, E; Wullkopf, U; Sturm, P; Kieslich, W; Born, R; Grossklos, M; Hatteh, R; Mueller, K; Ratschow, A; Valouch-Fornoff, C

2002-10-01

The idea of a 'zero emission city' is investigated by the Institut Wohnen und Umwelt on behalf of the Federal Minister of Education and Research. After describing the current situation and defining the key parameters of a 'zero emission city', settlement structures, power supply, production processes and transportation are analyzed and linked with the communal action level to obtain a framework for research, activities and actions. The study ends with recommendations for a research programme 'zero emission city'. (orig.) [German] Die von den Staedten der Industrielaender ausgehenden Emissionen stellen im Hinblick auf die globalen Belastungen wie z.B. Treibhauseffekt, Ozonabbau und Versauerung das Hauptproblem dar. Aus diesem Grunde bietet es sich an, den Gedanken der 'Null-Emissions-Stadt', der Vision einer moeglichst emissionsfreien Stadt, aufzugreifen und auf seine Tragfaehigkeit fuer innovative Handlungsmodelle forschungsstrategisch zu ueberpruefen. Das Bundesministerium fuer Bildung und Forschung hat das Institut Wohnen und Umwelt beauftragt, in einer Sondierungsstudie dieser Fragestellung nachzugehen. Nach der Festlegung der Ausgangsbedingungen und Eckpunkte der Vision 'Null-Emissions-Stadt' und der Analyse der vier Handlungsfelder Siedlungsstrukturen, Energieversorgung, Produktionsprozesse (Kreislaufwirtschaft) und Verkehr werden diese aufgegriffen und mit der kommunalen Handlungsebene verknuepft und zu einem Forschungs-, Handlungs- und moeglichen Aktionsrahmen zusammengefuegt. Die Studie schliesst mit Hinweisen fuer die Gestaltung eines Forschungsprogramms 'Null-Emissions-Stadt'. (orig.)

Glymphatic fluid transport controls paravascular clearance of AAV vectors from the brain

Science.gov (United States)

Murlidharan, Giridhar; Crowther, Andrew; Reardon, Rebecca A.; Song, Juan

2016-01-01

Adeno-associated viruses (AAV) are currently being evaluated in clinical trials for gene therapy of CNS disorders. However, host factors that influence the spread, clearance, and transduction efficiency of AAV vectors in the brain are not well understood. Recent studies have demonstrated that fluid flow mediated by aquaporin-4 (AQP4) channels located on astroglial end feet is essential for exchange of solutes between interstitial and cerebrospinal fluid. This phenomenon, which is essential for interstitial clearance of solutes from the CNS, has been termed glial-associated lymphatic transport or glymphatic transport. In the current study, we demonstrate that glymphatic transport profoundly affects various aspects of AAV gene transfer in the CNS. Altered localization of AQP4 in aged mouse brains correlated with significantly increased retention of AAV vectors in the parenchyma and reduced systemic leakage following ventricular administration. We observed a similar increase in AAV retention and transgene expression upon i.c.v. administration in AQP4–/– mice. Consistent with this observation, fluorophore-labeled AAV vectors showed markedly reduced flux from the ventricles of AQP4–/– mice compared with WT mice. These results were further corroborated by reduced AAV clearance from the AQP4-null brain, as demonstrated by reduced transgene expression and vector genome accumulation in systemic organs. We postulate that deregulation of glymphatic transport in aged and diseased brains could markedly affect the parenchymal spread, clearance, and gene transfer efficiency of AAV vectors. Assessment of biomarkers that report the kinetics of CSF flux in prospective gene therapy patients might inform variable treatment outcomes and guide future clinical trial design. PMID:27699236

Axial compartmentation of descending and ascending thin limbs of Henle's loops.

Science.gov (United States)

Westrick, Kristen Y; Serack, Bradley; Dantzler, William H; Pannabecker, Thomas L

2013-02-01

In the inner medulla, radial organization of nephrons and blood vessels around collecting duct (CD) clusters leads to two lateral interstitial regions and preferential intersegmental fluid and solute flows. As the descending (DTLs) and ascending thin limbs (ATLs) pass through these regions, their transepithelial fluid and solute flows are influenced by variable transepithelial solute gradients and structure-to-structure interactions. The goal of this study was to quantify structure-to-structure interactions, so as to better understand compartmentation and flows of transepithelial water, NaCl, and urea and generation of the axial osmotic gradient. To accomplish this, we determined lateral distances of AQP1-positive and AQP1-negative DTLs and ATLs from their nearest CDs, so as to gauge interactions with intercluster and intracluster lateral regions and interactions with interstitial nodal spaces (INSs). DTLs express reduced AQP1 and low transepithelial water permeability along their deepest segments. Deep AQP1-null segments, prebend segments, and ATLs lie equally near to CDs. Prebend segments and ATLs abut CDs and INSs throughout much of their descent and ascent, respectively; however, the distal 30% of ATLs of the longest loops lie distant from CDs as they approach the outer medullary boundary and have minimal interaction with INSs. These relationships occur regardless of loop length. Finally, we show that ascending vasa recta separate intercluster AQP1-positive DTLs from descending vasa recta, thereby minimizing dilution of gradients that drive solute secretion. We hypothesize that DTLs and ATLs enter and exit CD clusters in an orchestrated fashion that is important for generation of the corticopapillary solute gradient by minimizing NaCl and urea loss.

A class of algebraically general solutions of the Einstein-Maxwell equations for non-null electromagnetic fields

International Nuclear Information System (INIS)

Tupper, B.O.J.

1976-01-01

In a previous article (Gen. Rel. Grav.; 6 : 345 (1975)) the Einstein-Maxwell field equations for non-null electromagnetic fields were studied under the conditions that the null tetrad is parallel-propagated along both principal null congruences. A solution with twist and shear, but no expansion, was found and was conjectured to be the only expansion-free solution. Here it is shown that this conjecture is false; the general expansion-free solution is found to be a family of space-times depending on a single constant parameter which is the ratio of the (constant) twists of the two principal null congruences. (author)

Urea recycling contributes to nitrogen retention in calves fed milk replacer and low-protein solid feed.

Science.gov (United States)

Berends, Harma; van den Borne, Joost J G C; Røjen, Betina A; van Baal, Jürgen; Gerrits, Walter J J

2014-07-01

Urea recycling, with urea originating from catabolism of amino acids and hepatic detoxification of ammonia, is particularly relevant for ruminant animals, in which microbial protein contributes substantially to the metabolizable protein supply. However, the quantitative contribution of urea recycling to protein anabolism in calves during the transition from preruminants (milk-fed calves) to ruminants [solid feed (SF)-fed calves] is unknown. The aim of this study was to quantify urea recycling in milk-fed calves when provided with low-protein SF. Forty-eight calves [164 ± 1.6 kg body weight (BW)] were assigned to 1 of 4 SF levels [0, 9, 18, and 27 g of dry matter (DM) SF · kg BW(-0.75) · d⁻¹] provided in addition to an identical amount of milk replacer. Urea recycling was quantified after a 24-h intravenous infusion of [¹⁵N₂]urea by analyzing urea isotopomers in 68-h fecal and urinary collections. Real-time qPCR was used to measure gene expression levels of bovine urea transporter B (bUTB) and aquaglyceroporin-3 and aquaglyceroporin-7 in rumen wall tissues. For every incremental gram of DM SF intake (g DM · kg(0.75)), nitrogen intake increased by 0.70 g, and nitrogen retention increased by 0.55 g (P intake, but aquaglyceroporin-7 expression did not. We conclude that in addition to the increase in digested nitrogen, urea recycling contributes to the observed increase in nitrogen retention with increasing SF intake in milk-fed calves. Furthermore, ruminal bUTB and aquaglyceroporin-3 expression are upregulated with SF intake, which might be associated with urea recycling. © 2014 American Society for Nutrition.

IMPROVING INTERFEROMETRIC NULL DEPTH MEASUREMENTS USING STATISTICAL DISTRIBUTIONS: THEORY AND FIRST RESULTS WITH THE PALOMAR FIBER NULLER

International Nuclear Information System (INIS)

Hanot, C.; Riaud, P.; Absil, O.; Mennesson, B.; Martin, S.; Liewer, K.; Loya, F.; Mawet, D.; Serabyn, E.

2011-01-01

A new 'self-calibrated' statistical analysis method has been developed for the reduction of nulling interferometry data. The idea is to use the statistical distributions of the fluctuating null depth and beam intensities to retrieve the astrophysical null depth (or equivalently the object's visibility) in the presence of fast atmospheric fluctuations. The approach yields an accuracy much better (about an order of magnitude) than is presently possible with standard data reduction methods, because the astrophysical null depth accuracy is no longer limited by the magnitude of the instrumental phase and intensity errors but by uncertainties on their probability distributions. This approach was tested on the sky with the two-aperture fiber nulling instrument mounted on the Palomar Hale telescope. Using our new data analysis approach alone-and no observations of calibrators-we find that error bars on the astrophysical null depth as low as a few 10 -4 can be obtained in the near-infrared, which means that null depths lower than 10 -3 can be reliably measured. This statistical analysis is not specific to our instrument and may be applicable to other interferometers.

An equation satisfied by the tangent to a shear-free, geodesic, null congruence

International Nuclear Information System (INIS)

Hogan, P.A.; Dublin Inst. for Advanced Studies

1987-01-01

A tensorial equation satisfied by the tangent to a shear-free geodesic, null congruence is presented. If the congruence is neither twist-free nor expansion-free then the equation defines a second, unique, null direction previously obtained, using the spinor formalism, by Somers. Some further properties of the equation are discussed. (orig.)

ON THE NATURE OF RECONNECTION AT A SOLAR CORONAL NULL POINT ABOVE A SEPARATRIX DOME

International Nuclear Information System (INIS)

Pontin, D. I.; Priest, E. R.; Galsgaard, K.

2013-01-01

Three-dimensional magnetic null points are ubiquitous in the solar corona and in any generic mixed-polarity magnetic field. We consider magnetic reconnection at an isolated coronal null point whose fan field lines form a dome structure. Using analytical and computational models, we demonstrate several features of spine-fan reconnection at such a null, including the fact that substantial magnetic flux transfer from one region of field line connectivity to another can occur. The flux transfer occurs across the current sheet that forms around the null point during spine-fan reconnection, and there is no separator present. Also, flipping of magnetic field lines takes place in a manner similar to that observed in the quasi-separatrix layer or slip-running reconnection

Clausius entropy for arbitrary bifurcate null surfaces

International Nuclear Information System (INIS)

Baccetti, Valentina; Visser, Matt

2014-01-01

Jacobson’s thermodynamic derivation of the Einstein equations was originally applied only to local Rindler horizons. But at least some parts of that construction can usefully be extended to give meaningful results for arbitrary bifurcate null surfaces. As presaged in Jacobson’s original article, this more general construction sharply brings into focus the questions: is entropy objectively ‘real’? Or is entropy in some sense subjective and observer-dependent? These innocent questions open a Pandora’s box of often inconclusive debate. A consensus opinion, though certainly not universally held, seems to be that Clausius entropy (thermodynamic entropy, defined via a Clausius relation dS=đQ/T) should be objectively real, but that the ontological status of statistical entropy (Shannon or von Neumann entropy) is much more ambiguous, and much more likely to be observer-dependent. This question is particularly pressing when it comes to understanding Bekenstein entropy (black hole entropy). To perhaps further add to the confusion, we shall argue that even the Clausius entropy can often be observer-dependent. In the current article we shall conclusively demonstrate that one can meaningfully assign a notion of Clausius entropy to arbitrary bifurcate null surfaces—effectively defining a ‘virtual Clausius entropy’ for arbitrary ‘virtual (local) causal horizons’. As an application, we see that we can implement a version of the generalized second law (GSL) for this virtual Clausius entropy. This version of GSL can be related to certain (nonstandard) integral variants of the null energy condition. Because the concepts involved are rather subtle, we take some effort in being careful and explicit in developing our framework. In future work we will apply this construction to generalize Jacobson’s derivation of the Einstein equations. (paper)

Null vectors in superconformal quantum field theory

International Nuclear Information System (INIS)

Huang Chaoshang

1993-01-01

The superspace formulation of the N=1 superconformal field theory and superconformal Ward identities are used to give a precise definition of fusion. Using the fusion procedure, superconformally covariant differential equations are derived and consequently a complete and straightforward algorithm for finding null vectors in Verma modules of the Neveu-Schwarz algebra is given. (orig.)

Prognostic implication of aquaporin 1 overexpression in resected lung adenocarcinoma.

Science.gov (United States)

Bellezza, Guido; Vannucci, Jacopo; Bianconi, Fortunato; Metro, Giulio; Del Sordo, Rachele; Andolfi, Marco; Ferri, Ivana; Siccu, Paola; Ludovini, Vienna; Puma, Francesco; Sidoni, Angelo; Cagini, Lucio

2017-12-01

Aquaporins (AQPs) are a group of transmembrane water-selective channel proteins thought to play a role in the regulation of water permeability for plasma membranes. Indeed, high AQP levels have been suggested to promote the progression, invasion and metastasis of tumours. Specifically, AQP1 and AQP5 overexpression in lung adenocarcinoma (AC) have been suggested to be involved in molecular mechanisms in lung cancer. The aim of this retrospective cohort single-centre study was to assess both the levels of expression and therein the prognostic significance, regarding outcome of AQP1 and AQP5 in resected AC patients. Patients with histological diagnoses of lung AC submitted to pulmonary resection were included in this cohort study. Tissue microarrays containing cores from 185 ACs were prepared. AQP1 and AQP5 expressions were assessed by immunohistochemistry. Results were scored as either low (Score 0-2) or high (Score 3-9). Clinical data, pathological tumour-node-metastasis staging and follow-up were recorded. Multivariate Cox survival analysis and Fisher's t-test were performed. AQP1 overexpression was detected in 85 (46%) patients, while AQP5 overexpression was observed in 45 (24%) patients. AQP1 did not result being significantly correlated with clinical and pathological parameters, while AQP5 resulted more expressed in AC with mucinous and papillary predominant patterns. Patients with AQP1 overexpression had shorter disease-free survival (P = 0.001) compared with patients without AQP1 overexpression. Multivariate analysis confirmed that AQP1 overexpression was significantly associated with shorter disease-free survival (P = 0.001). Our results evidenced that AQP1 overexpression resulted in a shorter disease-free survival in lung AC patients. Being so, AQP1 overexpression might be an important prognostic marker in lung AC. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights

Covariant quantum mechanics on a null plane

International Nuclear Information System (INIS)

Leutwyler, H.; Stern, J.

1977-03-01

Lorentz invariance implies that the null plane wave functions factorize into a kinematical part describing the motion of the system as a whole and an inner wave function that involves the specific dynamical properties of the system - in complete correspondence with the non-relativistic situation. Covariance is equivalent to an angular condition which admits non-trivial solutions

Collapse and bounce of null fluids

OpenAIRE

Creelman, Bradley; Booth, Ivan

2016-01-01

Exact solutions describing the spherical collapse of null fluids can contain regions which violate the energy conditions. Physically the violations occur when the infalling matter continues to move inwards even when non-gravitational repulsive forces become stronger than gravity. In 1991 Ori proposed a resolution for these violations: spacetime surgery should be used to replace the energy condition violating region with an outgoing solution. The matter bounces. We revisit and implement this p...

Null balance type electrostatic generating voltmeters

International Nuclear Information System (INIS)

Mahant, A.K.; Sidhu, N.P.S.; Gupta, U.C.

1977-01-01

A description is given of a null balance type generating voltmeter for measuring high D.C. voltage upto about 400 kV. The paper discusses the principle of operation, design, calibration and performance of the instrument. Main advantages of the device are: (1) it does not load the high voltage source, (2) no physical connection is required with the H.T. terminal and (3) calibration is independent of the rotor's frequency and amplifier's gain. (author)

Zero emission city. Preliminary study; Null-Emissions-Stadt. Sondierungsstudie

Energy Technology Data Exchange (ETDEWEB)

Diefenbach, N.; Enseling, A.; Werner, P.; Flade, A.; Greiff, R.; Hennings, D.; Muehlich, E.; Wullkopf, U.; Sturm, P.; Kieslich, W.; Born, R.; Grossklos, M.; Hatteh, R.; Mueller, K.; Ratschow, A.; Valouch-Fornoff, C.

2002-10-01

The idea of a 'zero emission city' is investigated by the Institut Wohnen und Umwelt on behalf of the Federal Minister of Education and Research. After describing the current situation and defining the key parameters of a 'zero emission city', settlement structures, power supply, production processes and transportation are analyzed and linked with the communal action level to obtain a framework for research, activities and actions. The study ends with recommendations for a research programme 'zero emission city'. (orig.) [German] Die von den Staedten der Industrielaender ausgehenden Emissionen stellen im Hinblick auf die globalen Belastungen wie z.B. Treibhauseffekt, Ozonabbau und Versauerung das Hauptproblem dar. Aus diesem Grunde bietet es sich an, den Gedanken der 'Null-Emissions-Stadt', der Vision einer moeglichst emissionsfreien Stadt, aufzugreifen und auf seine Tragfaehigkeit fuer innovative Handlungsmodelle forschungsstrategisch zu ueberpruefen. Das Bundesministerium fuer Bildung und Forschung hat das Institut Wohnen und Umwelt beauftragt, in einer Sondierungsstudie dieser Fragestellung nachzugehen. Nach der Festlegung der Ausgangsbedingungen und Eckpunkte der Vision 'Null-Emissions-Stadt' und der Analyse der vier Handlungsfelder Siedlungsstrukturen, Energieversorgung, Produktionsprozesse (Kreislaufwirtschaft) und Verkehr werden diese aufgegriffen und mit der kommunalen Handlungsebene verknuepft und zu einem Forschungs-, Handlungs- und moeglichen Aktionsrahmen zusammengefuegt. Die Studie schliesst mit Hinweisen fuer die Gestaltung eines Forschungsprogramms 'Null-Emissions-Stadt'. (orig.)

A Model of Oxidative Stress Management: Moderation of Carbohydrate Metabolizing Enzymes in SOD1-Null Drosophila melanogaster

Science.gov (United States)

Bernard, Kristine E.; Parkes, Tony L.; Merritt, Thomas J. S.

2011-01-01

The response to oxidative stress involves numerous genes and mutations in these genes often manifest in pleiotropic ways that presumably reflect perturbations in ROS-mediated physiology. The Drosophila melanogaster SOD1-null allele (cSODn108) is proposed to result in oxidative stress by preventing superoxide breakdown. In SOD1-null flies, oxidative stress management is thought to be reliant on the glutathione-dependent antioxidants that utilize NADPH to cycle between reduced and oxidized form. Previous studies suggest that SOD1-null Drosophila rely on lipid catabolism for energy rather than carbohydrate metabolism. We tested these connections by comparing the activity of carbohydrate metabolizing enzymes, lipid and triglyceride concentration, and steady state NADPH:NADP+ in SOD1-null and control transgenic rescue flies. We find a negative shift in the activity of carbohydrate metabolizing enzymes in SOD1-nulls and the NADP+-reducing enzymes were found to have significantly lower activity than the other enzymes assayed. Little evidence for the catabolism of lipids as preferential energy source was found, as the concentration of lipids and triglycerides were not significantly lower in SOD1-nulls compared with controls. Using a starvation assay to impact lipids and triglycerides, we found that lipids were indeed depleted in both genotypes when under starvation stress, suggesting that oxidative damage was not preventing the catabolism of lipids in SOD1-null flies. Remarkably, SOD1-nulls were also found to be relatively resistant to starvation. Age profiles of enzyme activity, triglyceride and lipid concentration indicates that the trends observed are consistent over the average lifespan of the SOD1-nulls. Based on our results, we propose a model of physiological response in which organisms under oxidative stress limit the production of ROS through the down-regulation of carbohydrate metabolism in order to moderate the products exiting the electron transport chain. PMID

Vlasov Fluid stability of a 2-D plasma with a linear magnetic field null

International Nuclear Information System (INIS)

Kim, J.S.

1984-01-01

Vlasov Fluid stability of a 2-dimensional plasma near an O type magnetic null is investigated. Specifically, an elongated Z-pinch is considered, and applied to Field Reversed Configurations at Los Alamos National Laboratory by making a cylindrical approximation of the compact torus. The orbits near an elliptical O type null are found to be very complicated; the orbits are large and some are stochastic. The kinetic corrections to magnetohydrodynamics (MHD) are investigated by evaluating the expectation values of the growth rates of a Vlasov Fluid dispersion functional by using a set of trial functions based on ideal MHD. The dispersion functional involves fluid parts and orbit dependent parts. The latter involves phase integral of two time correlations. The phase integral is replaced by the time integral both for the regular and for the stochastic orbits. Two trial functions are used; one has a large displacement near the null and the other away from the null

[Effects of aquaporin-4 gene knockout on behavior changes and cerebral morphology during aging in mice].

Science.gov (United States)

Su, Shengan; Lu, Yunbi; Zhang, Weiping

2013-05-01

To investigate the effects of aquaporin-4 (AQP4) gene knockout on the behavior changes and cerebral morphology during aging in mice,and to compare that of young and aged mice between AQP4 knockout mice (AQP4(-/-)) and wild type mice (AQP4(+/+)). Fifty-eight CD-1 mice were divided into four groups: young (2-3 months old) AQP4(-/-), aged (17-19 months old) AQP4(-/-), young AQP4(+/+) and aged AQP4(+/+). The activity levels and exploring behavior of mice were tested in open field. The neurons were stained with toluidine blue and NeuN, the astrocytes and microglia were stained with GFAP and Iba-1, respectively. The morphological changes of neuron, astrocyte and microglia were then analyzed. Compared with young mice, the total walking distance in open field of aged AQP4(+/+) mice and aged AQP4(-/-) mice decreased 41.2% and 44.1%, respectively (Ptime in the central area of open field. The density of neuron in cortex of aged AQP4(+/+) mice and aged AQP4(-/-) mice decreased 19.6% and 15.8%, respectively (P<0.05), while there was no difference in the thickness of neuron cell body in hippocampus CA1 region. The density of astrocyte in hippocampus CA3 region of aged AQP4(+/+) mice and aged AQP4(-/-) mice increased 57.7% and 64.3%, respectively (P<0.001), while there was no difference in the area of astrocyte. The area of microglia in hippocampus CA3 region of aged AQP4(+/+) mice and aged AQP4(-/-) mice increased 46.9% and 52.0%, respectively (P<0.01), while there was no difference in the density of microglia. Compared with AQP4(+/+) mice, the young and aged AQP4(-/-) mice showed smaller area of astrocyte in hippocampus CA3 region, reduced 18.0% in young mice and 23.6% in aged mice. There was no difference between AQP4(+/+) mice and AQP4(-/-) mice for other observed indexes. AQP4 may be involved in change of astrocyte and astrocyte-related behaviors during aging. AQP4 gene knockout may have limited effects on the change of neuron, microglia and most neuronal behaviors in aging

The role of aquaporins in polycystic ovary syndrome - A way towards a novel drug target in PCOS.

Science.gov (United States)

Wawrzkiewicz-Jałowiecka, Agata; Kowalczyk, Karolina; Pluta, Dagmara; Blukacz, Łukasz; Madej, Paweł

2017-05-01

Aquaporins (AQPs) are transmembrane proteins, able to transport water (and in some cases also small solutes, e. g. glycerol) through the cell membrane. There are twelve types of aquaporins (AQP1-AQP12) expressed in mammalian reproductive systems. According to literature, many diseases of the reproductive organs are correlated with changes of AQPs expression and their malfunction. That is the case in the polycystic ovary syndrome (PCOS), where dysfunctions of AQPs 7-9 and alterations in its levels occur. In this work, we postulate how AQPs are involved in PCOS-related disorders, in order to emphasize their potential therapeutic meaning as a drug target. Our research allows for a surprising inference, that genetic mutation causing malfunction and/or decreased expression of aquaporins, may be incorporated in the popular insulin-dependent hypothesis of PCOS pathogenesis. What is more, changes in AQP's expression may affect the folliculogenesis and follicular atresia in PCOS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Null geodesics and embedding diagrams of the interior Schwarzschild--de Sitter spacetimes with uniform density

International Nuclear Information System (INIS)

Stuchlik, Zdenek; Hledik, Stanislav; Soltes, Jiri; Ostgaard, Erlend

2001-01-01

Null geodesics and embedding diagrams of central planes in the ordinary space geometry and the optical reference geometry of the interior Schwarzschild--de Sitter spacetimes with uniform density are studied. For completeness, both positive and negative values of the cosmological constant are considered. The null geodesics are restricted to the central planes of these spacetimes, and their properties can be reflected by an 'effective potential.' If the interior spacetime is extremely compact, the effective potential has a local maximum corresponding to a stable circular null geodesic around which bound null geodesics are concentrated. The upper limit on the size of the interior spacetimes containing bound null geodesics is R=3M, independently of the value of the cosmological constant. The embedding diagrams of the central planes of the ordinary geometry into three-dimensional Euclidean space are well defined for the complete interior of all spacetimes with a repulsive cosmological constant, but the planes cannot be embedded into the Euclidean space in the case of spacetimes with subcritical values of an attractive cosmological constant. On the other hand, the embedding diagrams of the optical geometry are well defined for all of the spacetimes, and the turning points of these diagrams correspond to the radii of the circular null geodesics. All the embedding diagrams, for both the ordinary and optical geometry, are smoothly matched to the corresponding embedding diagrams of the external vacuum Schwarzschild--de Sitter spacetimes

Nonparametric Regression Estimation for Multivariate Null Recurrent Processes

Directory of Open Access Journals (Sweden)

Biqing Cai

2015-04-01

Full Text Available This paper discusses nonparametric kernel regression with the regressor being a \\(d\\-dimensional \\(\\beta\\-null recurrent process in presence of conditional heteroscedasticity. We show that the mean function estimator is consistent with convergence rate \\(\\sqrt{n(Th^{d}}\\, where \\(n(T\\ is the number of regenerations for a \\(\\beta\\-null recurrent process and the limiting distribution (with proper normalization is normal. Furthermore, we show that the two-step estimator for the volatility function is consistent. The finite sample performance of the estimate is quite reasonable when the leave-one-out cross validation method is used for bandwidth selection. We apply the proposed method to study the relationship of Federal funds rate with 3-month and 5-year T-bill rates and discover the existence of nonlinearity of the relationship. Furthermore, the in-sample and out-of-sample performance of the nonparametric model is far better than the linear model.

Asymptotic symmetries of Rindler space at the horizon and null infinity

International Nuclear Information System (INIS)

Chung, Hyeyoun

2010-01-01

We investigate the asymptotic symmetries of Rindler space at null infinity and at the event horizon using both systematic and ad hoc methods. We find that the approaches that yield infinite-dimensional asymptotic symmetry algebras in the case of anti-de Sitter and flat spaces only give a finite-dimensional algebra for Rindler space at null infinity. We calculate the charges corresponding to these symmetries and confirm that they are finite, conserved, and integrable, and that the algebra of charges gives a representation of the asymptotic symmetry algebra. We also use relaxed boundary conditions to find infinite-dimensional asymptotic symmetry algebras for Rindler space at null infinity and at the event horizon. We compute the charges corresponding to these symmetries and confirm that they are finite and integrable. We also determine sufficient conditions for the charges to be conserved on-shell, and for the charge algebra to give a representation of the asymptotic symmetry algebra. In all cases, we find that the central extension of the charge algebra is trivial.

Null Geodesic Congruences, Asymptotically-Flat Spacetimes and Their Physical Interpretation

Directory of Open Access Journals (Sweden)

Timothy M. Adamo

2009-09-01

Full Text Available A priori, there is nothing very special about shear-free or asymptotically shear-free null geodesic congruences. Surprisingly, however, they turn out to possess a large number of fascinating geometric properties and to be closely related, in the context of general relativity, to a variety of physically significant effects. It is the purpose of this paper to try to fully develop these issues. This work starts with a detailed exposition of the theory of shear-free and asymptotically shear-free null geodesic congruences, i.e., congruences with shear that vanishes at future conformal null infinity. A major portion of the exposition lies in the analysis of the space of regular shear-free and asymptotically shear-free null geodesic congruences. This analysis leads to the space of complex analytic curves in complex Minkowski space. They in turn play a dominant role in the applications. The applications center around the problem of extracting interior physical properties of an asymptotically-flat spacetime directly from the asymptotic gravitational (and Maxwell field itself, in analogy with the determination of total charge by an integral over the Maxwell field at infinity or the identification of the interior mass (and its loss by (Bondi’s integrals of the Weyl tensor, also at infinity. More specifically, we will see that the asymptotically shear-free congruences lead us to an asymptotic definition of the center-of-mass and its equations of motion. This includes a kinematic meaning, in terms of the center-of-mass motion, for the Bondi three-momentum. In addition, we obtain insights into intrinsic spin and, in general, angular momentum, including an angular-momentum–conservation law with well-defined flux terms. When a Maxwell field is present, the asymptotically shear-free congruences allow us to determine/define at infinity a center-of-charge world line and intrinsic magnetic dipole moment.

Null Geodesic Congruences, Asymptotically-Flat Spacetimes and Their Physical Interpretation

Directory of Open Access Journals (Sweden)

Timothy M. Adamo

2012-01-01

Full Text Available A priori, there is nothing very special about shear-free or asymptotically shear-free null geodesic congruences. Surprisingly, however, they turn out to possess a large number of fascinating geometric properties and to be closely related, in the context of general relativity, to a variety of physically significant effects. It is the purpose of this paper to try to fully develop these issues. This work starts with a detailed exposition of the theory of shear-free and asymptotically shear-free null geodesic congruences, i.e., congruences with shear that vanishes at future conformal null infinity. A major portion of the exposition lies in the analysis of the space of regular shear-free and asymptotically shear-free null geodesic congruences. This analysis leads to the space of complex analytic curves in an auxiliary four-complex dimensional space, H-space. They in turn play a dominant role in the applications. The applications center around the problem of extracting interior physical properties of an asymptotically-flat spacetime directly from the asymptotic gravitational (and Maxwell field itself, in analogy with the determination of total charge by an integral over the Maxwell field at infinity or the identification of the interior mass (and its loss by (Bondi's integrals of the Weyl tensor, also at infinity. More specifically, we will see that the asymptotically shear-free congruences lead us to an asymptotic definition of the center-of-mass and its equations of motion. This includes a kinematic meaning, in terms of the center-of-mass motion, for the Bondi three-momentum. In addition, we obtain insights into intrinsic spin and, in general, angular momentum, including an angular-momentum--conservation law with well-defined flux terms. When a Maxwell field is present, the asymptotically shear-free congruences allow us to determine/define at infinity a center-of-charge world line and intrinsic magnetic dipole moment.

Null Geodesic Congruences, Asymptotically-Flat Spacetimes and Their Physical Interpretation.

Science.gov (United States)

Adamo, Timothy M; Newman, Ezra T; Kozameh, Carlos

2012-01-01

A priori, there is nothing very special about shear-free or asymptotically shear-free null geodesic congruences. Surprisingly, however, they turn out to possess a large number of fascinating geometric properties and to be closely related, in the context of general relativity, to a variety of physically significant effects. It is the purpose of this paper to try to fully develop these issues. This work starts with a detailed exposition of the theory of shear-free and asymptotically shear-free null geodesic congruences, i.e., congruences with shear that vanishes at future conformal null infinity. A major portion of the exposition lies in the analysis of the space of regular shear-free and asymptotically shear-free null geodesic congruences. This analysis leads to the space of complex analytic curves in an auxiliary four-complex dimensional space, [Formula: see text]-space. They in turn play a dominant role in the applications. The applications center around the problem of extracting interior physical properties of an asymptotically-flat spacetime directly from the asymptotic gravitational (and Maxwell) field itself, in analogy with the determination of total charge by an integral over the Maxwell field at infinity or the identification of the interior mass (and its loss) by (Bondi's) integrals of the Weyl tensor, also at infinity. More specifically, we will see that the asymptotically shear-free congruences lead us to an asymptotic definition of the center-of-mass and its equations of motion. This includes a kinematic meaning, in terms of the center-of-mass motion, for the Bondi three-momentum. In addition, we obtain insights into intrinsic spin and, in general, angular momentum, including an angular-momentum-conservation law with well-defined flux terms. When a Maxwell field is present, the asymptotically shear-free congruences allow us to determine/define at infinity a center-of-charge world line and intrinsic magnetic dipole moment.

Bi-dimensional null model analysis of presence-absence binary matrices.

Science.gov (United States)

Strona, Giovanni; Ulrich, Werner; Gotelli, Nicholas J

2018-01-01

Comparing the structure of presence/absence (i.e., binary) matrices with those of randomized counterparts is a common practice in ecology. However, differences in the randomization procedures (null models) can affect the results of the comparisons, leading matrix structural patterns to appear either "random" or not. Subjectivity in the choice of one particular null model over another makes it often advisable to compare the results obtained using several different approaches. Yet, available algorithms to randomize binary matrices differ substantially in respect to the constraints they impose on the discrepancy between observed and randomized row and column marginal totals, which complicates the interpretation of contrasting patterns. This calls for new strategies both to explore intermediate scenarios of restrictiveness in-between extreme constraint assumptions, and to properly synthesize the resulting information. Here we introduce a new modeling framework based on a flexible matrix randomization algorithm (named the "Tuning Peg" algorithm) that addresses both issues. The algorithm consists of a modified swap procedure in which the discrepancy between the row and column marginal totals of the target matrix and those of its randomized counterpart can be "tuned" in a continuous way by two parameters (controlling, respectively, row and column discrepancy). We show how combining the Tuning Peg with a wise random walk procedure makes it possible to explore the complete null space embraced by existing algorithms. This exploration allows researchers to visualize matrix structural patterns in an innovative bi-dimensional landscape of significance/effect size. We demonstrate the rational and potential of our approach with a set of simulated and real matrices, showing how the simultaneous investigation of a comprehensive and continuous portion of the null space can be extremely informative, and possibly key to resolving longstanding debates in the analysis of ecological

Impact of null genotypes of GSTT1 and GSTM1 with uterine leiomyoma risk in Iranian population.

Science.gov (United States)

Mostafavi, Salva Sadat; Ebrahimi, Ahmad; Sadat, Seyed Mehdi; Davari Tanha, Fatemeh; Aghasadeghi, Mohammad Reza; Bahramali, Golnaz; Abbasi Ranjbar, Parinaz; Sadeghifard, Vida; Javadi, Foozieh

2016-04-01

Few studies have investigated the role of the GSTM1 and GSTT1 genes in uterine leiomyoma. Therefore, in the current study the distribution of these genotypes in Iranian women and susceptibility to uterine leiomyoma was investigated. Blood samples of 50 patients with uterine leiomyoma and 50 healthy individual controls were collected in this cross-sectional study. Genomic DNA was extracted, and subsequently GSTM1 and GSTT1 null genotypes were detected by the Gap-polymerase chain reaction method. A total of 42% of patients appeared to lack GSTM1 enzyme activity due to the presence of an extended deletion (GSTM1 0/0 genotype), compared with 18% in a control group (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.35-9.37; P leiomyoma and null GSTM1 and GSTT1 genotypes among Iranian patients. Our data support the involvement of GSTM1 and GSTT1 in uterine leiomyoma liability, and especially its role as a genetic factor in the occurrence of this disease. © 2016 Japan Society of Obstetrics and Gynecology.

Expression Profiling of Differentiating Emerin-Null Myogenic Progenitor Identifies Molecular Pathways Implicated in Their Impaired Differentiation

Directory of Open Access Journals (Sweden)

Ashvin Iyer

2017-10-01

Full Text Available Mutations in the gene encoding emerin cause Emery-Dreifuss muscular dystrophy (EDMD, a disorder causing progressive skeletal muscle wasting, irregular heart rhythms and contractures of major tendons. RNA sequencing was performed on differentiating wildtype and emerin-null myogenic progenitors to identify molecular pathways implicated in EDMD, 340 genes were uniquely differentially expressed during the transition from day 0 to day 1 in wildtype cells. 1605 genes were uniquely expressed in emerin-null cells; 1706 genes were shared among both wildtype and emerin-null cells. One thousand and forty-seven transcripts showed differential expression during the transition from day 1 to day 2. Four hundred and thirty-one transcripts showed altered expression in both wildtype and emerin-null cells. Two hundred and ninety-five transcripts were differentially expressed only in emerin-null cells and 321 transcripts were differentially expressed only in wildtype cells. DAVID, STRING and Ingenuity Pathway Analysis identified pathways implicated in impaired emerin-null differentiation, including cell signaling, cell cycle checkpoints, integrin signaling, YAP/TAZ signaling, stem cell differentiation, and multiple muscle development and myogenic differentiation pathways. Functional enrichment analysis showed biological functions associated with the growth of muscle tissue and myogenesis of skeletal muscle were inhibited. The large number of differentially expressed transcripts upon differentiation induction suggests emerin functions during transcriptional reprograming of progenitors to committed myoblasts.

The Many Null Distributions of Person Fit Indices.

Science.gov (United States)

Molenaar, Ivo W.; Hoijtink, Herbert

1990-01-01

Statistical properties of person fit indices are reviewed as indicators of the extent to which a person's score pattern is in agreement with a measurement model. Distribution of a fit index and ability-free fit evaluation are discussed. The null distribution was simulated for a test of 20 items. (SLD)

Stitching interferometry of high numerical aperture cylindrical optics without using a fringe-nulling routine.

Science.gov (United States)

Peng, Junzheng; Wang, Qingquan; Peng, Xiang; Yu, Yingjie

2015-11-01

Stitching interferometry is a common method for measuring the figure error of high numerical aperture optics. However, subaperture measurement usually requires a fringe-nulling routine, thus making the stitching procedure complex and time-consuming. The challenge when measuring a surface without a fringe-nulling routine is that the rays no longer perpendicularly hit the surface. This violation of the null-test condition can lead to high fringe density and introduce high-order misalignment aberrations into the measurement result. This paper demonstrates that the high-order misalignment aberrations can be characterized by low-order misalignment aberrations; then, an efficient method is proposed to separate the high-order misalignment aberrations from subaperture data. With the proposed method, the fringe-nulling routine is not required. Instead, the subaperture data is measured under a nonzero fringe pattern. Then, all possible misalignment aberrations are removed with the proposed method. Finally, the full aperture map is acquired by connecting all subaperture data together. Experimental results showing the feasibility of the proposed procedure are presented.

Demonstrating Broadband Billion-to-One Contrast with the Visible Nulling Coronagraph

Science.gov (United States)

Hicks, Brian A.; Lyon, Richard G.; Petrone, Peter, III; Miller, Ian J.; Bolcar, Matthew R.; Clampin, Mark; Helmbrecht, Michael A.; Mallik, Udayan

2015-01-01

The key to broadband operation of the Visible Nulling Coronagraph (VNC) is achieving a condition of quasi- achromatic destructive interference between combined beams. Here we present efforts towards meeting this goal using Fresnel rhombs in each interferometric arm as orthogonally aligned half wave phase retarders. The milestone goal of the demonstration is to achieve 1 × 10-9 contrast at 2/D over a 40 nm bandpass centered at 633 nm. Rhombs have been designed and fabricated, and a multi-step approach to alignment using coarse positioners for each rhomb and pair has been developed to get within range of piezo stages used for fine positioning. The previously demonstrated narrowband VNC sensing and control approach that uses a segmented deformable mirror is being adapted to broadband to include fine positioning of the piezo-mounted rhombs, all demonstrated in a low-pressure environment.

Demonstrating broadband billion-to-one contrast with the Visible Nulling Coronagraph

Science.gov (United States)

Hicks, Brian A.; Lyon, Richard G.; Petrone, Peter; Miller, Ian J.; Bolcar, Matthew R.; Clampin, Mark; Helmbrecht, Michael A.; Mallik, Udayan

2015-09-01

The key to broadband operation of the Visible Nulling Coronagraph (VNC) is achieving a condition of quasi-achromatic destructive interference between combined beams. Here we present efforts towards meeting this goal using Fresnel rhombs in each interferometric arm as orthogonally aligned half wave phase retarders. The milestone goal of the demonstration is to achieve 1 × 10-9 contrast at 2λ/D over a 40 nm bandpass centered at 633 nm. Rhombs have been designed and fabricated, and a multi-step approach to alignment using coarse positioners for each rhomb and pair has been developed to get within range of piezo stages used for fine positioning. The previously demonstrated narrowband VNC sensing and control approach that uses a segmented deformable mirror is being adapted to broadband to include fine positioning of the piezo-mounted rhombs, all demonstrated in a low-pressure environment.

The Harm Done to Reproducibility by the Culture of Null Hypothesis Significance Testing.

Science.gov (United States)

Lash, Timothy L

2017-09-15

In the last few years, stakeholders in the scientific community have raised alarms about a perceived lack of reproducibility of scientific results. In reaction, guidelines for journals have been promulgated and grant applicants have been asked to address the rigor and reproducibility of their proposed projects. Neither solution addresses a primary culprit, which is the culture of null hypothesis significance testing that dominates statistical analysis and inference. In an innovative research enterprise, selection of results for further evaluation based on null hypothesis significance testing is doomed to yield a low proportion of reproducible results and a high proportion of effects that are initially overestimated. In addition, the culture of null hypothesis significance testing discourages quantitative adjustments to account for systematic errors and quantitative incorporation of prior information. These strategies would otherwise improve reproducibility and have not been previously proposed in the widely cited literature on this topic. Without discarding the culture of null hypothesis significance testing and implementing these alternative methods for statistical analysis and inference, all other strategies for improving reproducibility will yield marginal gains at best. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Calculation of null points in SPAIR, FLAIR, and STIR. Part 2. Application to pelvic diffusion-weighted imaging with SPAIR at 3T

International Nuclear Information System (INIS)

Kita, Miho; Kawano, Kazuhiro; Kometani, Katsuya; Kondo, Toshihiko; Shimamoto, Kazuhiro; Tanaka, Humihiro; Oda, Hideyuki; Kojima, Akihiro; Sato, Morio

2013-01-01

Diffusion-weighted imaging (DWI) requires adequate fat suppression because of its sensitivity to chemical shift artifacts, especially at 3 Tesla (T). We investigated the utility of calculating the inversion time of the null point (TI null ) in pelvic DWI with spectral attenuated inversion recovery (SPAIR) at 3 T for obtaining adequate fat suppression. Thirteen volunteers underwent pelvic SPAIR-DWI using various SPAIR inversion delay times (TI) at 5-ms intervals in the range of the calculated TI null ±25 ms. The degree of fat suppression was evaluated into 3 grades and was compared among the various SPAIR-TIs with the calculated TI null . In 65 cases of prostatic disease, we evaluated the ratio of adequate fat suppression obtained using the calculated TI null . We obtained adequate fat suppression in all 13 volunteers and in 61 (94%) of the 65 patients using the calculated TI null . Fat suppression was best when the calculated TI null was used (P null (P null increased. In conclusion, this method of calculating the TI null may be useful for obtaining adequate fat suppression for pelvic SPAIR-DWI at 3T. (author)

Segmented Aperture Interferometric Nulling Testbed (SAINT) II: component systems update

Science.gov (United States)

Hicks, Brian A.; Bolcar, Matthew R.; Helmbrecht, Michael A.; Petrone, Peter; Burke, Elliot; Corsetti, James; Dillon, Thomas; Lea, Andrew; Pellicori, Samuel; Sheets, Teresa; Shiri, Ron; Agolli, Jack; DeVries, John; Eberhardt, Andrew; McCabe, Tyler

2017-09-01

This work presents updates to the coronagraph and telescope components of the Segmented Aperture Interferometric Nulling Testbed (SAINT). The project pairs an actively-controlled macro-scale segmented mirror with the Visible Nulling Coronagraph (VNC) towards demonstrating capabilities for the future space observatories needed to directly detect and characterize a significant sample of Earth-sized worlds around nearby stars in the quest for identifying those which may be habitable and possibly harbor life. Efforts to improve the VNC wavefront control optics and mechanisms towards repeating narrowband results are described. A narrative is provided for the design of new optical components aimed at enabling broadband performance. Initial work with the hardware and software interface for controlling the segmented telescope mirror is also presented.

Integrable structures and the quantization of free null initial data for gravity

Science.gov (United States)

Fuchs, Andreas; Reisenberger, Michael P.

2017-09-01

Variables for constraint free null canonical vacuum general relativity are presented which have simple Poisson brackets that facilitate quantization. Free initial data for vacuum general relativity on a pair of intersecting null hypersurfaces has been known since the 1960s. These consist of the ‘main’ data which are set on the bulk of the two null hypersurfaces, and additional ‘surface’ data set only on their intersection 2-surface. More recently the complete set of Poisson brackets of such data has been obtained. However the complexity of these brackets is an obstacle to their quantization. Part of this difficulty may be overcome using methods from the treatment of cylindrically symmetric gravity. Specializing from general to cylindrically symmetric solutions changes the Poisson algebra of the null initial data surprisingly little, but cylindrically symmetric vacuum general relativity is an integrable system, making powerful tools available. Here a transformation is constructed at the cylindrically symmetric level which maps the main initial data to new data forming a Poisson algebra for which an exact deformation quantization is known. (Although an auxiliary condition on the data has been quantized only in the asymptotically flat case, and a suitable representation of the algebra of quantum data by operators on a Hilbert space has not yet been found.) The definition of the new main data generalizes naturally to arbitrary, symmetryless gravitational fields, with the Poisson brackets retaining their simplicity. The corresponding generalization of the quantization is however ambiguous and requires further analysis.

Percentiles of the null distribution of 2 maximum lod score tests.

Science.gov (United States)

Ulgen, Ayse; Yoo, Yun Joo; Gordon, Derek; Finch, Stephen J; Mendell, Nancy R

2004-01-01

We here consider the null distribution of the maximum lod score (LOD-M) obtained upon maximizing over transmission model parameters (penetrance values, dominance, and allele frequency) as well as the recombination fraction. Also considered is the lod score maximized over a fixed choice of genetic model parameters and recombination-fraction values set prior to the analysis (MMLS) as proposed by Hodge et al. The objective is to fit parametric distributions to MMLS and LOD-M. Our results are based on 3,600 simulations of samples of n = 100 nuclear families ascertained for having one affected member and at least one other sibling available for linkage analysis. Each null distribution is approximately a mixture p(2)(0) + (1 - p)(2)(v). The values of MMLS appear to fit the mixture 0.20(2)(0) + 0.80chi(2)(1.6). The mixture distribution 0.13(2)(0) + 0.87chi(2)(2.8). appears to describe the null distribution of LOD-M. From these results we derive a simple method for obtaining critical values of LOD-M and MMLS. Copyright 2004 S. Karger AG, Basel

Alfvén wave dynamics at the neighborhood of a 2.5D magnetic null-point

Science.gov (United States)

Sabri, S.; Vasheghani Farahani, S.; Ebadi, H.; Hosseinpour, M.; Fazel, Z.

2018-05-01

The aim of the present study is to highlight the energy transfer via the interaction of magnetohydrodynamic waves with a 2.5D magnetic null-point in a finite plasma-β regime of the solar corona. An initially symmetric Alfvén pulse at a specific distance from a magnetic null-point is kicked towards the isothermal null-point. A shock-capturing Godunov-type PLUTO code is used to solve the ideal magnetohydrodynamic set equations in the context of wave-plasma energy transfer. As the Alfvén wave propagates towards the magnetic null-point it experiences speed lowering which ends up in releasing energy along the separatrices. In this line owing to the Alfvén wave, a series of events take place that contribute towards coronal heating. Nonlinear induced waves are by products of the torsional Alfvén interaction with magnetic null-points. The energy of these induced waves which are fast magnetoacoustic (transverse) and slow magnetoacoustic (longitudinal) waves are supplied by the Alfvén wave. The nonlinearly induced density perturbations are proportional to the Alfvén wave energy loss. This supplies energy for the propagation of fast and slow magnetoacoustic waves, where in contrast to the fast wave the slow wave experiences a continuous energy increase. As such, the slow wave may transfer its energy to the medium at later times, maintaining a continuous heating mechanism at the neighborhood of a magnetic null-point.

Limit structure of future null infinity tangent-topology of the event horizon and gravitational wave tail

International Nuclear Information System (INIS)

Tomizawa, Shinya; Siino, Masaru

2006-01-01

We investigated the relation between the behaviour of gravitational waves at late time and the limit structure of future null infinity tangent which will determine the topology of the event horizon far in the future. In the present paper, we mainly consider a spacetime with two black holes. Although in most cases, the black holes coalesce and the event horizon is topologically a single sphere far in the future, there are several possibilities that the black holes never coalesce and such exact solutions as examples. In our formulation, the tangent vector of future null infinity is, under conformal embedding, related to the number of black holes far in the future through the Poincare-Hopf theorem. Under the conformal embedding, the topology of the event horizon far in the future will be affected by the geometrical structure of the future null infinity. In this paper, we relate the behaviour of Weyl curvature to this limit behaviour of the generator vector of the future null infinity. We show if Weyl curvature decays sufficiently slowly at late time in the neighbourhood of future null infinity, two black holes never coalesce

Maxwell, Yang-Mills, Weyl and eikonal fields defined by any null shear-free congruence

Science.gov (United States)

Kassandrov, Vladimir V.; Rizcallah, Joseph A.

We show that (specifically scaled) equations of shear-free null geodesic congruences on the Minkowski space-time possess intrinsic self-dual, restricted gauge and algebraic structures. The complex eikonal, Weyl 2-spinor, SL(2, ℂ) Yang-Mills and complex Maxwell fields, the latter produced by integer-valued electric charges (“elementary” for the Kerr-like congruences), can all be explicitly associated with any shear-free null geodesic congruence. Using twistor variables, we derive the general solution of the equations of the shear-free null geodesic congruence (as a modification of the Kerr theorem) and analyze the corresponding “particle-like” field distributions, with bounded singularities of the associated physical fields. These can be obtained in a straightforward algebraic way and exhibit nontrivial collective dynamics simulating physical interactions.

From GLC to double-null coordinates and illustration with static black holes

Energy Technology Data Exchange (ETDEWEB)

Nugier, Fabien, E-mail: fnugier@ntu.edu.tw [Leung Center for Cosmology and Particle Astrophysics, National Taiwan University, Taipei, 10617 Taiwan (China)

2016-09-01

We present a system of coordinates deriving directly from the so-called Geodesic Light-Cone (GLC) coordinates and made of two null scalars intersecting on a 2-dimensional sphere parameterized by two constant angles along geodesics. These coordinates are shown to be equivalent to the well-known double-null coordinates. As GLC, they present interesting properties for cosmology and astrophysics. We discuss this latter topic for static black holes, showing simple descriptions for the metric or particles and photons trajectories. We also briefly comment on the time of flight of ultra-relativistic particles.

SwissProt search result: AK061782 [KOME

Lifescience Database Archive (English)

Full Text Available AK061782 001-039-E03 (P47865) Aquaporin-1 (AQP-1) (Aquaporin-CHIP) (Water channel p...rotein for red blood cells and kidney proximal tubule) (Water channel protein CHIP29) AQP1_BOVIN 9e-45 ...

SwissProt search result: AK104464 [KOME

Lifescience Database Archive (English)

Full Text Available AK104464 006-301-C06 (P47865) Aquaporin-1 (AQP-1) (Aquaporin-CHIP) (Water channel p...rotein for red blood cells and kidney proximal tubule) (Water channel protein CHIP29) AQP1_BOVIN 9e-28 ...

SwissProt search result: AK099616 [KOME

Lifescience Database Archive (English)

Full Text Available AK099616 J013050J20 (P47865) Aquaporin-1 (AQP-1) (Aquaporin-CHIP) (Water channel pr...otein for red blood cells and kidney proximal tubule) (Water channel protein CHIP29) AQP1_BOVIN 9e-28 ...

SwissProt search result: AK099141 [KOME

Lifescience Database Archive (English)

Full Text Available AK099141 J023055A02 (P47865) Aquaporin-1 (AQP-1) (Aquaporin-CHIP) (Water channel pr...otein for red blood cells and kidney proximal tubule) (Water channel protein CHIP29) AQP1_BOVIN 9e-28 ...

SwissProt search result: AK099015 [KOME

Lifescience Database Archive (English)

Full Text Available AK099015 J013116H02 (P47865) Aquaporin-1 (AQP-1) (Aquaporin-CHIP) (Water channel pr...otein for red blood cells and kidney proximal tubule) (Water channel protein CHIP29) AQP1_BOVIN 9e-28 ...

SwissProt search result: AK107700 [KOME

Lifescience Database Archive (English)

Full Text Available AK107700 002-132-C10 (P47865) Aquaporin-1 (AQP-1) (Aquaporin-CHIP) (Water channel p...rotein for red blood cells and kidney proximal tubule) (Water channel protein CHIP29) AQP1_BOVIN 9e-18 ...

Spectratyping analysis of the islet-reactive T cell repertoire in diabetic NOD Igμnull mice after polyclonal B cell reconstitution

Directory of Open Access Journals (Sweden)

Sercarz Eli E

2011-07-01

Full Text Available Abstract Background Non Obese Diabetic mice lacking B cells (NOD.Igμnull mice do not develop diabetes despite their susceptible background. Upon reconstitution of B cells using a chimera approach, animals start developing diabetes at 20 weeks of age. Methods We have used the spectratyping technique to follow the T cell receptor (TCR V beta repertoire of NOD.Igμnull mice following B cell reconstitution. This technique provides an unbiased approach to understand the kinetics of TCR expansion. We have also analyzed the TCR repertoire of reconstituted animals receiving cyclophosphamide treatment and following tissue transplants to identify common aggressive clonotypes. Results We found that B cell reconstitution of NOD.Igμnull mice induces a polyclonal TCR repertoire in the pancreas 10 weeks later, gradually diversifying to encompass most BV families. Interestingly, these clonotypic BV expansions are mainly confined to the pancreas and are absent from pancreatic lymph nodes or spleens. Cyclophosphamide-induced diabetes at 10 weeks post-B cell reconstitution reorganized the predominant TCR repertoires by removing potential regulatory clonotypes (BV1, BV8 and BV11 and increasing the frequency of others (BV4, BV5S2, BV9, BV16-20. These same clonotypes are more frequently present in neonatal pancreatic transplants under the kidney capsule of B-cell reconstituted diabetic NOD.Igμnull mice, suggesting their higher invasiveness. Phenotypic analysis of the pancreas-infiltrating lymphocytes during diabetes onset in B cell reconstituted animals show a predominance of CD19+ B cells with a B:T lymphocyte ratio of 4:1. In contrast, in other lymphoid organs (pancreatic lymph nodes and spleens analyzed by FACS, the B:T ratio was 1:1. Lymphocytes infiltrating the pancreas secrete large amounts of IL-6 and are of Th1 phenotype after CD3-CD28 stimulation in vitro. Conclusions Diabetes in NOD.Igμnull mice appears to be caused by a polyclonal repertoire of T cell

Diversity-Multiplexing-Nulling Trade-Off Analysis of Multiuser MIMO System for Intercell Interference Coordination

Directory of Open Access Journals (Sweden)

Jinwoo Kim

2017-01-01

Full Text Available A fundamental performance trade-off of multicell multiuser multiple-input multiple-output (MU-MIMO systems is explored for achieving intercell and intracell interference-free conditions. In particular, we analyze the three-dimensional diversity-multiplexing-nulling trade-off (DMNT among the diversity order (i.e., the slope of the error performance curve, multiplexing order (i.e., the number of users that are simultaneously served by MU-MIMO, and nulling order (i.e., the number of users with zero interference in a victim cell. This trade-off quantifies the performance of MU-MIMO in terms of its diversity and multiplexing order, while nulling the intercell interference toward the victim cell in the neighbor. First, we design a precoding matrix to mitigate both intercell and intracell interference for a linear precoding-based MU-MIMO system. Then, the trade-off relationship is obtained by analyzing the distribution of the signal-to-noise ratio (SNR at the user terminals. Furthermore, we demonstrate how DMNT can be applied to estimate the long-term throughput for each mobile station, which allows for determining the optimal number of multiplexing order and throughput loss due to the interference nulling.

Null Lens Assembly for X-Ray Mirror Segments

Science.gov (United States)

Robinson, David W.

2011-01-01

A document discusses a null lens assembly that allows laser interferometry of 60 deg. slumped glass mirror segments used in x-ray mirrors. The assembly consists of four lenses in precise alignment to each other, with incorporated piezoelectric nanometer stepping actuators to position the lenses in six degrees of freedom for positioning relative to each other.

Euclidean null controllability of perturbed infinite delay systems with ...

African Journals Online (AJOL)

Euclidean null controllability of perturbed infinite delay systems with limited control. ... Open Access DOWNLOAD FULL TEXT ... The results are established by placing conditions on the perturbation function which guarantee that, if the linear control base system is completely Euclidean controllable, then the perturbed system ...

Magnetic Reconnection at a Three-dimensional Solar Null Point

DEFF Research Database (Denmark)

Frederiksen, Jacob Trier; Baumann, Gisela; Galsgaard, Klaus

2012-01-01

Using a specific solar null point reconnection case studied by Masson et al (2009; ApJ 700, 559) we investigate the dependence of the reconnection rate on boundary driving speed, numerical resolution, type of resistivity (constant or numerical), and assumed stratification (constant density or sol...

Characterization of the Stabilized Test Bench of Nulling Interferometry PERSÉE

Science.gov (United States)

Lozi, Julien; Ollivier, M.; Cassaing, F.; Le Duigou, J.; CNES; Onera/Dota/HRA; IAS; LESIA; OCA; TAS

2013-01-01

There are two problems with the observation of exoplanets: the contrast between the planet and the star and their very low separation. One technique solving these problems is nulling interferometry: two pupils are recombined to make a destructive interference on the star, and their base is adjusted to create a constructive interference on the planet. However, to ensure a sufficient extinction of the star, the optical path difference between the beams must be around the nanometer, and the pointing must be better than one hundredth of Airy disk, despite the external disturbances.To validate the critical points of such a space mission, a laboratory demonstrator, PERSÉE, was defined by a consortium led by the french space agency CNES, including IAS, LESIA, ONERA, OCA and Thales Alenia Space and integrated in Paris Observatory. This bench simulates the entire space mission (interferometer and nanometric cophasing system). Its goal is to deliver and maintain an extinction of 10^-4 stable at better than 10^-5 over a few hours in the presence of typical injected disturbances.My thesis work consisted in integrating the bench in successive stages and to develop calibration procedures. This helped me to characterize the critical elements separately before grouping them. After having implemented the control loops of the cophasing system, their precise analysis helped me to reduce down to 0.3 nm rms the residual OPD, and 0.4 % of the Airy disk the residual tip/tilt, despite disturbances of tens of nanometers, consisting of several tens of vibrational frequencies between 1 and 100 Hz. This has been achieved by the implementation of a linear quadratic Gaussian controller, parameterized by the preliminary measurement of the disturbance to minimize. Thanks to these excellent results, I obtained on the band [1.65 - 2.45] µm a record null rate of 8.8x10^-6 stabilized at 9x10^-7 over a few hours, a decade better than the original specifications. An extrapolation of these results to

Orexin Receptor Antagonism Improves Sleep and Reduces Seizures in Kcna1-null Mice.

Science.gov (United States)

Roundtree, Harrison M; Simeone, Timothy A; Johnson, Chaz; Matthews, Stephanie A; Samson, Kaeli K; Simeone, Kristina A

2016-02-01

Comorbid sleep disorders occur in approximately one-third of people with epilepsy. Seizures and sleep disorders have an interdependent relationship where the occurrence of one can exacerbate the other. Orexin, a wake-promoting neuropeptide, is associated with sleep disorder symptoms. Here, we tested the hypothesis that orexin dysregulation plays a role in the comorbid sleep disorder symptoms in the Kcna1-null mouse model of temporal lobe epilepsy. Rest-activity was assessed using infrared beam actigraphy. Sleep architecture and seizures were assessed using continuous video-electroencephalography-electromyography recordings in Kcna1-null mice treated with vehicle or the dual orexin receptor antagonist, almorexant (100 mg/kg, intraperitoneally). Orexin levels in the lateral hypothalamus/perifornical region (LH/P) and hypothalamic pathology were assessed with immunohistochemistry and oxygen polarography. Kcna1-null mice have increased latency to rapid eye movement (REM) sleep onset, sleep fragmentation, and number of wake epochs. The numbers of REM and non-REM (NREM) sleep epochs are significantly reduced in Kcna1-null mice. Severe seizures propagate to the wake-promoting LH/P where injury is apparent (indicated by astrogliosis, blood-brain barrier permeability, and impaired mitochondrial function). The number of orexin-positive neurons is increased in the LH/P compared to wild-type LH/P. Treatment with a dual orexin receptor antagonist significantly increases the number and duration of NREM sleep epochs and reduces the latency to REM sleep onset. Further, almorexant treatment reduces the incidence of severe seizures and overall seizure burden. Interestingly, we report a significant positive correlation between latency to REM onset and seizure burden in Kcna1-null mice. Dual orexin receptor antagonists may be an effective sleeping aid in epilepsy, and warrants further study on their somnogenic and ant-seizure effects in other epilepsy models. © 2016 Associated

Regional and Large-Scale Climate Influences on Tree-Ring Reconstructed Null Zone Position in San Francisco Bay

Science.gov (United States)

Stahle, D.; Griffin, D.; Cleaveland, M.; Fye, F.; Meko, D.; Cayan, D.; Dettinger, M.; Redmond, K.

2007-05-01

A new network of 36 moisture sensitive tree-ring chronologies has been developed in and near the drainage basins of the Sacramento and San Joaquin Rivers. The network is based entirely on blue oak (Quercus douglasii), which is a California endemic found from the lower forest border up into the mixed conifer zone in the Coast Ranges, Sierra Nevada, and Cascades. These blue oak tree-ring chronologies are highly correlated with winter-spring precipitation totals, Sacramento and San Joaquin streamflow, and with seasonal variations in salinity and null zone position in San Francisco Bay. Null zone is the non-tidal bottom water location where density-driven salinity and river-driven freshwater currents balance (zero flow). It is the area of highest turbidity, water residence time, sediment accumulation, and net primary productivity in the estuary. Null zone position is measured by the distance from the Golden Gate of the 2 per mil bottom water isohaline and is primarily controlled by discharge from the Sacramento and San Joaquin Rivers (and ultimately by winter-spring precipitation). The location of the null zone is an estuarine habitat indicator, a policy variable used for ecosystem management, and can have a major impact on biological resources in the San Francisco estuary. Precipitation-sensitive blue oak chronologies can be used to estimate null zone position based on the strong biogeophysical interaction among terrestrial, aquatic, and estuarine ecosystems, orchestrated by precipitation. The null zone reconstruction is 626-years long and provides a unique long term perspective on the interannual to decadal variability of this important estuarine habitat indicator. Consecutive two-year droughts (or longer) allow the null zone to shrink into the confined upper reaches of Suisun Bay, causing a dramatic reduction in phytoplankton production and favoring colonization of the estuary by marine biota. The reconstruction indicates an approximate 10 year recurrence interval

Evidence of Positive Selection of Aquaporins Genes from Pontoporia blainvillei during the Evolutionary Process of Cetaceans.

Directory of Open Access Journals (Sweden)

Simone Lima São Pedro

Full Text Available Marine mammals are well adapted to their hyperosmotic environment. Several morphological and physiological adaptations for water conservation and salt excretion are known to be present in cetaceans, being responsible for regulating salt balance. However, most previous studies have focused on the unique renal physiology of marine mammals, but the molecular bases of these mechanisms remain poorly explored. Many genes have been identified to be involved in osmotic regulation, including the aquaporins. Considering that aquaporin genes were potentially subject to strong selective pressure, the aim of this study was to analyze the molecular evolution of seven aquaporin genes (AQP1, AQP2, AQP3, AQP4, AQP6, AQP7, and AQP9 comparing the lineages of cetaceans and terrestrial mammals.Our results demonstrated strong positive selection in cetacean-specific lineages acting only in the gene for AQP2 (amino acids 23, 83, 107,179, 180, 181, 182, whereas no selection was observed in terrestrial mammalian lineages. We also analyzed the changes in the 3D structure of the aquaporin 2 protein. Signs of strong positive selection in AQP2 sites 179, 180, 181, and 182 were unexpectedly identified only in the baiji lineage, which was the only river dolphin examined in this study. Positive selection in aquaporins AQP1 (45, AQP4 (74, AQP7 (342, 343, 356 was detected in cetaceans and artiodactyls, suggesting that these events are not related to maintaining water and electrolyte homeostasis in seawater.Our results suggest that the AQP2 gene might reflect different selective pressures in maintaining water balance in cetaceans, contributing to the passage from the terrestrial environment to the aquatic. Further studies are necessary, especially those including other freshwater dolphins, who exhibit osmoregulatory mechanisms different from those of marine cetaceans for the same essential task of maintaining serum electrolyte balance.

Relative controllability and null controllability of linear delay systems ...

African Journals Online (AJOL)

Necessary and sufficient conditions are established for the relative, absolute controllability and null controllability of the generalized linear delay system and its discrete prototype. The paper presents illuminating examples on previous controllability results by Manitius and Olbrot [7] and carries over the results of Onwuatu [8] ...

Local modular Hamiltonians from the quantum null energy condition

Science.gov (United States)

Koeller, Jason; Leichenauer, Stefan; Levine, Adam; Shahbazi-Moghaddam, Arvin

2018-03-01

The vacuum modular Hamiltonian K of the Rindler wedge in any relativistic quantum field theory is given by the boost generator. Here we investigate the modular Hamiltonian for more general half-spaces which are bounded by an arbitrary smooth cut of a null plane. We derive a formula for the second derivative of the modular Hamiltonian with respect to the coordinates of the cut which schematically reads K''=Tv v . This formula can be integrated twice to obtain a simple expression for the modular Hamiltonian. The result naturally generalizes the standard expression for the Rindler modular Hamiltonian to this larger class of regions. Our primary assumptions are the quantum null energy condition—an inequality between the second derivative of the von Neumann entropy of a region and the stress tensor—and its saturation in the vacuum for these regions. We discuss the validity of these assumptions in free theories and holographic theories to all orders in 1 /N .

"Time sweet time": circadian characterization of galectin-1 null mice

Directory of Open Access Journals (Sweden)

Rabinovich Gabriel A

2010-04-01

Full Text Available Abstract Background Recent evidence suggests a two-way interaction between the immune and circadian systems. Circadian control of immune factors, as well as the effect of immunological variables on circadian rhythms, might be key elements in both physiological and pathological responses to the environment. Among these relevant factors, galectin-1 is a member of a family of evolutionarily-conserved glycan-binding proteins with both extracellular and intracellular effects, playing important roles in immune cell processes and inflammatory responses. Many of these actions have been studied through the use of mice with a null mutation in the galectin-1 (Lgals1 gene. To further analyze the role of endogenous galectin-1 in vivo, we aimed to characterize the circadian behavior of galectin-1 null (Lgals1-/- mice. Methods We analyzed wheel-running activity in light-dark conditions, constant darkness, phase responses to light pulses (LP at circadian time 15, and reentrainment to 6 hour shifts in light-dark schedule in wild-type (WT and Lgals1-/- mice. Results We found significant differences in free-running period, which was longer in mutant than in WT mice (24.02 vs 23.57 h, p alpha (14.88 vs. 12.35 circadian h, p Conclusions Given the effect of a null mutation on circadian period and entrainment, we indicate that galectin-1 could be involved in the regulation of murine circadian rhythmicity. This is the first study implicating galectin-1 in the mammalian circadian system.

Relative null controllability of linear systems with multiple delays in ...

African Journals Online (AJOL)

varying multiple delays in state and control are developed. If the uncontrolled system is uniformly asymptotically stable, and if the linear system is controllable, then the linear system is null controllable. Journal of the Nigerian Association of ...

In vivo time-gated diffuse correlation spectroscopy at quasi-null source-detector separation.

Science.gov (United States)

Pagliazzi, M; Sekar, S Konugolu Venkata; Di Sieno, L; Colombo, L; Durduran, T; Contini, D; Torricelli, A; Pifferi, A; Mora, A Dalla

2018-06-01

We demonstrate time domain diffuse correlation spectroscopy at quasi-null source-detector separation by using a fast time-gated single-photon avalanche diode without the need of time-tagging electronics. This approach allows for increased photon collection, simplified real-time instrumentation, and reduced probe dimensions. Depth discriminating, quasi-null distance measurement of blood flow in a human subject is presented. We envision the miniaturization and integration of matrices of optical sensors of increased spatial resolution and the enhancement of the contrast of local blood flow changes.

Abnormal nociception and opiate sensitivity of STOP null mice exhibiting elevated levels of the endogenous alkaloid morphine

Directory of Open Access Journals (Sweden)

Aunis Dominique

2010-12-01

Full Text Available Abstract Background- Mice deficient for the stable tubule only peptide (STOP display altered dopaminergic neurotransmission associated with severe behavioural defects including disorganized locomotor activity. Endogenous morphine, which is present in nervous tissues and synthesized from dopamine, may contribute to these behavioral alterations since it is thought to play a role in normal and pathological neurotransmission. Results- In this study, we showed that STOP null brain structures, including cortex, hippocampus, cerebellum and spinal cord, contain high endogenous morphine amounts. The presence of elevated levels of morphine was associated with the presence of a higher density of mu opioid receptor with a higher affinity for morphine in STOP null brains. Interestingly, STOP null mice exhibited significantly lower nociceptive thresholds to thermal and mechanical stimulations. They also had abnormal behavioural responses to the administration of exogenous morphine and naloxone. Low dose of morphine (1 mg/kg, i.p. produced a significant mechanical antinociception in STOP null mice whereas it has no effect on wild-type mice. High concentration of naloxone (1 mg/kg was pronociceptive for both mice strain, a lower concentration (0.1 mg/kg was found to increase the mean mechanical nociceptive threshold only in the case of STOP null mice. Conclusions- Together, our data show that STOP null mice displayed elevated levels of endogenous morphine, as well as an increase of morphine receptor affinity and density in brain. This was correlated with hypernociception and impaired pharmacological sensitivity to mu opioid receptor ligands.

Twisting null geodesic congruences and the Einstein-Maxwell equations

International Nuclear Information System (INIS)

Newman, Ezra T; Silva-Ortigoza, Gilberto

2006-01-01

In a recent article, we returned to the study of asymptotically flat solutions of the vacuum Einstein equations with a rather unconventional point of view. The essential observation in that work was that from a given asymptotically flat vacuum spacetime with a given Bondi shear, one can find a class of asymptotically shear-free (but, in general, twisting) null geodesic congruences where the class was uniquely given up to the arbitrary choice of a complex analytic 'worldline' in a four-dimensional complex space. By imitating certain terms in the Weyl tensor that are found in the algebraically special type II metrics, this complex worldline could be made unique and given-or assigned-the physical meaning as the complex centre of mass. Equations of motion for this case were found. The purpose of the present work is to extend those results to asymptotically flat solutions of the Einstein-Maxwell equations. Once again, in this case, we get a class of asymptotically shear-free null geodesic congruences depending on a complex worldline in the same four-dimensional complex space. However in this case there will be, in general, two distinct but uniquely chosen worldlines, one of which can be assigned as the complex centre of charge while the other could be called the complex centre of mass. Rather than investigating the situation where there are two distinct complex worldlines, we study instead the special degenerate case where the two worldlines coincide, i.e., where there is a single unique worldline. This mimics the case of algebraically special Einstein-Maxwell fields where the degenerate principle null vector of the Weyl tensor coincides with a Maxwell principle null vector. Again we obtain equations of motion for this worldline-but explicitly found here only in an approximation. Though there are ambiguities in assigning physical meaning to different terms it appears as if reliance on the Kerr and charged Kerr metrics and classical electromagnetic radiation theory helps

Thrombospondin 2-null mice display an altered brain foreign body response to polyvinyl alcohol sponge implants

International Nuclear Information System (INIS)

Tian Weiming; Kyriakides, Themis R

2009-01-01

Thrombospondin (TSP)-2 is a matricellular protein that participates in the processes of tissue repair and the foreign body response. In addition, TSP2 has been shown to influence synaptogenesis and recovery of the brain following stroke. In the present study we investigated the response following the implantation of polyvinyl alcohol (PVA) sponges in the brain. PVA sponges were implanted into the brain cortex of wild type and TSP2-null mice for a period of 4 and 8 weeks and the response was analyzed by histochemistry and quantitative immunohistochemistry. TSP2 expression was detected in the interstices of the sponge and co-localized with the extracellular matrix and astrocytes. PVA sponge invasion in TSP2-null mice was characterized by dense deposition of extracellular matrix and increased invasion of reactive astrocytes and macrophages/microglia. Furthermore, the angiogenic response was elevated and the detection of mouse serum albumin (MSA) in the brain cortex indicated excessive vessel leakage, suggesting that TSP2 plays a role in the repair/maintenance of the blood brain barrier. Finally, immunostaining demonstrated an increase in the levels of matrix metalloproteinase (MMP)-2 and MMP-9. Taken together, our observations support a role for TSP2 as critical determinant of the brain response to biomaterials.

Genome-wide identification of Jatropha curcas aquaporin genes and the comparative analysis provides insights into the gene family expansion and evolution in Hevea brasiliensis

Directory of Open Access Journals (Sweden)

Zhi eZou

2016-03-01

Full Text Available Aquaporins (AQPs are channel-forming integral membrane proteins that transport water and other small solutes across biological membranes. Despite the vital role of AQPs, to date, little is known in physic nut (Jatropha curcas L., Euphorbiaceae, an important non-edible oilseed crop with great potential for the production of biodiesel. In this study, 32 AQP genes were identified from the physic nut genome and the family number is relatively small in comparison to 51 in another Euphorbiaceae plant, rubber tree (Hevea brasiliensis Muell. Arg.. Based on the phylogenetic analysis, the JcAQPs were assigned to five subfamilies, i.e., 9 plasma membrane intrinsic proteins (PIPs, 9 tonoplast intrinsic proteins (TIPs, 8 NOD26-like intrinsic proteins (NIPs, 2 X intrinsic proteins (XIPs and 4 small basic intrinsic proteins (SIPs. Like rubber tree and other plant species, functional prediction based on the aromatic/arginine selectivity filter, Froger’s positions and specificity-determining positions showed a remarkable difference in substrate specificity among subfamilies of JcAQPs. Genome-wide comparative analysis revealed the specific expansion of PIP and TIP subfamilies in rubber tree and the specific gene loss of the XIP subfamily in physic nut. Furthermore, by analyzing deep transcriptome sequencing data, the expression evolution especially the expression divergence of duplicated HbAQP genes was also investigated and discussed. Results obtained from this study not only provide valuable information for future functional analysis and utilization of Jc/HbAQP genes, but also provide a useful reference to survey the gene family expansion and evolution in Euphorbiaceae plants and other plant species.

Aquaporins 6-12 in the human eye

DEFF Research Database (Denmark)

Tran, Thuy Linh; Bek, Toke; Holm, Lars

2012-01-01

Purpose: Aquaporins (AQPs) are widely expressed and have diverse distribution patterns in the eye. AQPs 0-5 have been localized at the cellular level in human eyes. We investigated the presence of the more recently discovered AQPs 6-12 in the human eye. Methods: RT-PCR was performed on fresh tissue...... from two human eyes divided into the cornea, corneal limbus, ciliary body and iris, lens, choroid, optic nerve, retina and sclera. Each structure was examined to detect the mRNA of AQPs 6-12. Twenty-one human eyes were examined using immunohistochemical and immunofluorescence techniques to determine...... was detected in the corneal epithelium, corneal endothelium, trabecular meshwork endothelium, ciliary epithelia, lens epithelium, the inner and outer limiting membrane of the retina, the retinal pigment epithelium and the capillary endothelium of all parts of the eye. AQP9 immunolabelling was detected...

Lovelock vacua with a recurrent null vector field

Czech Academy of Sciences Publication Activity Database

Ortaggio, Marcello

2018-01-01

Roč. 97, č. 4 (2018), č. článku 044051. ISSN 2470-0010 R&D Projects: GA ČR GA13-10042S Institutional support: RVO:67985840 Keywords : Lovelock gravity * recurrent null vector field Subject RIV: BA - General Mathematics OBOR OECD: Applied mathematics Impact factor: 4.568, year: 2016 https://journals.aps.org/prd/abstract/10.1103/PhysRevD.97.044051

Lovelock vacua with a recurrent null vector field

Czech Academy of Sciences Publication Activity Database

Ortaggio, Marcello

2018-01-01

Roč. 97, č. 4 (2018), č. článku 044051. ISSN 2470-0010 R&D Projects: GA ČR GA13-10042S Institutional support: RVO:67985840 Keywords : Lovelock gravity * recurrent null vector field Subject RIV: BA - General Mathematics OBOR OECD: Applied mathematics Impact factor: 4.568, year: 2016 https://journals. aps .org/prd/abstract/10.1103/PhysRevD.97.044051

Shaping Up the Practice of Null Hypothesis Significance Testing.

Science.gov (United States)

Wainer, Howard; Robinson, Daniel H.

2003-01-01

Discusses criticisms of null hypothesis significance testing (NHST), suggesting that historical use of NHST was reasonable, and current users should read Sir Ronald Fisher's applied work. Notes that modifications to NHST and interpretations of its outcomes might better suit the needs of modern science. Concludes that NHST is most often useful as…

Luxembourg in the Early Days of the EEC: Null Player or Not?

Directory of Open Access Journals (Sweden)

Alexander Mayer

2018-05-01

Full Text Available Voters whose yes-or-no decision never makes a difference to the outcome in a simple voting game are known as “null players”. Luxembourg’s role in the Council of Ministers during the first period of the European Economic Community (EEC is often cited as a real-world case. The paper contrasts the textbook claim that Luxembourg was a null player with a more comprehensive picture of Luxembourg’s role in EEC’s voting system. The assessment of Luxembourg’s voting power is sensitive to the role played by the European Commission in the decision-making procedure and the measurement concepts underlying power evaluations.

Comparative proteomic analysis of normal and collagen IX null mouse cartilage reveals altered extracellular matrix composition and novel components of the collagen IX interactome.

Science.gov (United States)

Brachvogel, Bent; Zaucke, Frank; Dave, Keyur; Norris, Emma L; Stermann, Jacek; Dayakli, Münire; Koch, Manuel; Gorman, Jeffrey J; Bateman, John F; Wilson, Richard

2013-05-10

Collagen IX is an integral cartilage extracellular matrix component important in skeletal development and joint function. Proteomic analysis and validation studies revealed novel alterations in collagen IX null cartilage. Matrilin-4, collagen XII, thrombospondin-4, fibronectin, βig-h3, and epiphycan are components of the in vivo collagen IX interactome. We applied a proteomics approach to advance our understanding of collagen IX ablation in cartilage. The cartilage extracellular matrix is essential for endochondral bone development and joint function. In addition to the major aggrecan/collagen II framework, the interacting complex of collagen IX, matrilin-3, and cartilage oligomeric matrix protein (COMP) is essential for cartilage matrix stability, as mutations in Col9a1, Col9a2, Col9a3, Comp, and Matn3 genes cause multiple epiphyseal dysplasia, in which patients develop early onset osteoarthritis. In mice, collagen IX ablation results in severely disturbed growth plate organization, hypocellular regions, and abnormal chondrocyte shape. This abnormal differentiation is likely to involve altered cell-matrix interactions but the mechanism is not known. To investigate the molecular basis of the collagen IX null phenotype we analyzed global differences in protein abundance between wild-type and knock-out femoral head cartilage by capillary HPLC tandem mass spectrometry. We identified 297 proteins in 3-day cartilage and 397 proteins in 21-day cartilage. Components that were differentially abundant between wild-type and collagen IX-deficient cartilage included 15 extracellular matrix proteins. Collagen IX ablation was associated with dramatically reduced COMP and matrilin-3, consistent with known interactions. Matrilin-1, matrilin-4, epiphycan, and thrombospondin-4 levels were reduced in collagen IX null cartilage, providing the first in vivo evidence for these proteins belonging to the collagen IX interactome. Thrombospondin-4 expression was reduced at the mRNA level

Increased Oocyte Degeneration and Follicular Atresia during the Estrous Cycle in Anti-Müllerian Hormone Null Mice

NARCIS (Netherlands)

Visser, Jenny A.; Durlinger, Alexandra L.L.; Peters, Isolde J.J.; Heuvel, Edwin R. van den; Rose, Ursula M.; Kramer, Piet; Jong, Frank H. de; Themmen, Axel P.N.

2007-01-01

Anti-Müllerian hormone (AMH) plays an important role in folliculogenesis. AMH null mice display an increased recruitment of primordial follicles. Nevertheless, these mice do not have proportionally more preovulatory follicles. Therefore, AMH null mice provide an interesting genetic model to study

Pair of null gravitating shells: III. Algebra of Dirac's observables

International Nuclear Information System (INIS)

Kouletsis, I; Hajicek, P

2002-01-01

The study of the two-shell system started in 'pair of null gravitating shells I and II' is continued. The pull back of the Liouville form to the constraint surface, which contains complete information about the Poisson brackets of Dirac observables, is computed in the singular double-null Eddington-Finkelstein (DNEF) gauge. The resulting formula shows that the variables conjugate to the Schwarzschild masses of the intershell spacetimes are simple combinations of the values of the DNEF coordinates on these spacetimes at the shells. The formula is valid for any number of in- and outgoing shells. After applying it to the two-shell system, the symplectic form is calculated for each component of the physical phase space; regular coordinates are found, defining it as a symplectic manifold. The symplectic transformation between the initial and final values of observables for the shell-crossing case is given

Magnetic Nulls and Super-radial Expansion in the Solar Corona

Energy Technology Data Exchange (ETDEWEB)

Gibson, Sarah E.; Dalmasse, Kevin; Tomczyk, Steven; Toma, Giuliana de; Burkepile, Joan; Galloy, Michael [National Center for Atmospheric Research, 3080 Center Green Drive, Boulder, CO 80301 (United States); Rachmeler, Laurel A. [NASA Marshall Space Flight Center, Huntsville, AL 35811 (United States); Rosa, Marc L. De, E-mail: sgibson@ucar.edu [Lockheed Martin Solar and Astrophysics Laboratory, 3251 Hanover Street B/252, Palo Alto, CA 94304 (United States)

2017-05-10

Magnetic fields in the Sun’s outer atmosphere—the corona—control both solar-wind acceleration and the dynamics of solar eruptions. We present the first clear observational evidence of coronal magnetic nulls in off-limb linearly polarized observations of pseudostreamers, taken by the Coronal Multichannel Polarimeter (CoMP) telescope. These nulls represent regions where magnetic reconnection is likely to act as a catalyst for solar activity. CoMP linear-polarization observations also provide an independent, coronal proxy for magnetic expansion into the solar wind, a quantity often used to parameterize and predict the solar wind speed at Earth. We introduce a new method for explicitly calculating expansion factors from CoMP coronal linear-polarization observations, which does not require photospheric extrapolations. We conclude that linearly polarized light is a powerful new diagnostic of critical coronal magnetic topologies and the expanding magnetic flux tubes that channel the solar wind.

Altered extracellular matrix remodeling and angiogenesis in sponge granulomas of thrombospondin 2-null mice.

Science.gov (United States)

Kyriakides, T R; Zhu, Y H; Yang, Z; Huynh, G; Bornstein, P

2001-10-01

The matricellular angiogenesis inhibitor, thrombospondin (TSP) 2, has been shown to be an important modulator of wound healing and the foreign body response. Specifically, TSP2-null mice display improved healing with minimal scarring and form well-vascularized foreign body capsules. In this study we performed subcutaneous implantation of sponges and investigated the resulting angiogenic and fibrogenic responses. Histological and immunohistochemical analysis of sponges, excised at 7, 14, and 21 days after implantation, revealed significant differences between TSP2-null and wild-type mice. Most notably, TSP2-null mice exhibited increased angiogenesis and fibrotic encapsulation of the sponge. However, invasion of dense tissue was compromised, even though its overall density was increased. Furthermore, histomorphometry and biochemical assays demonstrated a significant increase in the extracellular distribution of matrix metalloproteinase (MMP) 2, but no change in the levels of active transforming growth factor-beta(1). The alterations in neovascularization, dense tissue invasion, and MMP2 in TSP2-null mice coincided with the deposition of TSP2 in the extracellular matrix of wild-type animals. These observations support the proposed role of TSP2 as a modulator of angiogenesis and matrix remodeling during tissue repair. In addition, they provide in vivo evidence for a newly proposed function of TSP2 as a modulator of extracellular MMP2 levels.

Generalized Robertson-Walker Space-Time Admitting Evolving Null Horizons Related to a Black Hole Event Horizon.

Science.gov (United States)

Duggal, K L

2016-01-01

A new technique is used to study a family of time-dependent null horizons, called " Evolving Null Horizons " (ENHs), of generalized Robertson-Walker (GRW) space-time [Formula: see text] such that the metric [Formula: see text] satisfies a kinematic condition. This work is different from our early papers on the same issue where we used (1 + n )-splitting space-time but only some special subcases of GRW space-time have this formalism. Also, in contrast to previous work, we have proved that each member of ENHs is totally umbilical in [Formula: see text]. Finally, we show that there exists an ENH which is always a null horizon evolving into a black hole event horizon and suggest some open problems.

Multi-Segment Radius Measurement Using an Absolute Distance Meter Through a Null Assembly

Science.gov (United States)

Merle, Cormic; Wick, Eric; Hayden, Joseph

2011-01-01

This system was one of the test methods considered for measuring the radius of curvature of one or more of the 18 segmented mirrors that form the 6.5 m diameter primary mirror (PM) of the James Webb Space Telescope (JWST). The assembled telescope will be tested at cryogenic temperatures in a 17-m diameter by 27-m high vacuum chamber at the Johnson Space Center. This system uses a Leica Absolute Distance Meter (ADM), at a wavelength of 780 nm, combined with beam-steering and beam-shaping optics to make a differential distance measurement between a ring mirror on the reflective null assembly and individual PM segments. The ADM is located inside the same Pressure-Tight Enclosure (PTE) that houses the test interferometer. The PTE maintains the ADM and interferometer at ambient temperature and pressure so that they are not directly exposed to the telescope s harsh cryogenic and vacuum environment. This system takes advantage of the existing achromatic objective and reflective null assembly used by the test interferometer to direct four ADM beamlets to four PM segments through an optical path that is coincident with the interferometer beam. A mask, positioned on a linear slide, contains an array of 1.25 mm diameter circular subapertures that map to each of the 18 PM segments as well as six positions around the ring mirror. A down-collimated 4 mm ADM beam simultaneously covers 4 adjacent PM segment beamlets and one ring mirror beamlet. The radius, or spacing, of all 18 segments can be measured with the addition of two orthogonally-oriented scanning pentaprisms used to steer the ADM beam to any one of six different sub-aperture configurations at the plane of the ring mirror. The interferometer beam, at a wavelength of 687 nm, and the ADM beamlets, at a wavelength of 780 nm, pass through the objective and null so that the rays are normally incident on the parabolic PM surface. After reflecting off the PM, both the ADM and interferometer beams return to their respective

Shearfree congruences of null geodesics and Killing tensors

International Nuclear Information System (INIS)

Dietz, W.; Ruediger, R.

1980-01-01

In this communication, the mutual connections between quantities that are generalizations of the notion of a a Killing vector field are investigated. A classification of these quantities in terms of a complex vector field αsub(a) is given. A common feature of all these quantities is that they imply the existence of a pair of shearfree geodetic null congruences. There are no explicit restrictions posed on the Ricci tensor. (author)

Two-loop string theory on null compactifications

International Nuclear Information System (INIS)

Cove, Henry C.D.; Szabo, Richard J.

2006-01-01

We compute the two-loop contributions to the free energy in the null compactification of perturbative string theory at finite temperature. The cases of bosonic, type II and heterotic strings are all treated. The calculation exploits an explicit reductive parametrization of the moduli space of infinite-momentum frame string worldsheets in terms of branched cover instantons. Various arithmetic and physical properties of the instanton sums are described. Applications to symmetric product orbifold conformal field theories and to the matrix string theory conjecture are also briefly discussed

Generalized frame of reference with null congruence

International Nuclear Information System (INIS)

Ferrarese, G.; Antonelli, R.

2000-01-01

The paper derives the main properties of a generalized frame of reference with a null congruence (light flux), by means of adapted non-holonomic techniques; then it studies the geometry of the space-time in terms of non-orthogonal projection: longitudinal and transverse covariant derivatives and corresponding commutation formulae, decomposition of the Riemann and gravitational tensors, lie derivatives of the Ricci rotation coefficients, transverse Bianchi identity. Application to the (absolute and relative) light flux: kinematical characteristics and screen, Sachs theorems etc. are also given

The Segmented Aperture Interferometric Nulling Testbed (SAINT) I: overview and air-side system description

Science.gov (United States)

Hicks, Brian A.; Lyon, Richard G.; Petrone, Peter; Ballard, Marlin; Bolcar, Matthew R.; Bolognese, Jeff; Clampin, Mark; Dogoda, Peter; Dworzanski, Daniel; Helmbrecht, Michael A.; Koca, Corina; Shiri, Ron

2016-07-01

This work presents an overview of the Segmented Aperture Interferometric Nulling Testbed (SAINT), a project that will pair an actively-controlled macro-scale segmented mirror with the Visible Nulling Coronagraph (VNC). SAINT will incorporate the VNC's demonstrated wavefront sensing and control system to refine and quantify end-to-end high-contrast starlight suppression performance. This pathfinder testbed will be used as a tool to study and refine approaches to mitigating instabilities and complex diffraction expected from future large segmented aperture telescopes.

The sense of water in the blowfly Protophormia terraenovae.

Science.gov (United States)

Solari, Paolo; Masala, Carla; Falchi, Angela Maria; Sollai, Giorgia; Liscia, Anna

2010-12-01

The gustatory system of the blowfly, Protophormia terraenovae, is a relatively simple biological model for studies on chemosensory input and behavioral output. It appears to have renewed interest as a model for studies on the role of water channels, namely aquaporins or aquaglyceroporins, in water detection. To this end, we investigated the presence of water channels, their role in "water" and "salt" cell responsiveness and the transduction mechanism involved. For the first time our electrophysiological results point to the presence of an aquaglyceroporin in the chemoreceptor membrane of the "water" cell in the blowfly taste chemosensilla whose transduction mechanism ultimately involves an intracellular calcium increase and consequently cell depolarization. This hypothesis is also supported by calcium imaging data following proper stimulation. This mechanism is triggered by "water" cell stimulation with hypotonic solutions and/or solutes such as glycerol which crosses the membrane by way of aquaglyceroporins. Behavioral output indicates that the "sense" of water in blowflies is definitely not dependent on the "water" cell only, but also on the "salt" cell sensitivity. These findings also hypothesize a new role for aquaglyceroporin in spiking cell excitability. Copyright © 2010 Elsevier Ltd. All rights reserved.

Nav 1.8-null mice show stimulus-dependent deficits in spinal neuronal activity

Directory of Open Access Journals (Sweden)

Wood John N

2006-02-01

Full Text Available Abstract Background The voltage gated sodium channel Nav 1.8 has a highly restricted expression pattern to predominantly nociceptive peripheral sensory neurones. Behaviourally Nav 1.8-null mice show an increased acute pain threshold to noxious mechanical pressure and also deficits in inflammatory and visceral, but not neuropathic pain. Here we have made in vivo electrophysiology recordings of dorsal horn neurones in intact anaesthetised Nav 1.8-null mice, in response to a wide range of stimuli to further the understanding of the functional roles of Nav 1.8 in pain transmission from the periphery to the spinal cord. Results Nav 1.8-null mice showed marked deficits in the coding by dorsal horn neurones to mechanical, but not thermal, -evoked responses over the non-noxious and noxious range compared to littermate controls. Additionally, responses evoked to other stimulus modalities were also significantly reduced in Nav 1.8-null mice where the reduction observed to pinch > brush. The occurrence of ongoing spontaneous neuronal activity was significantly less in mice lacking Nav 1.8 compared to control. No difference was observed between groups in the evoked activity to electrical activity of the peripheral receptive field. Conclusion This study demonstrates that deletion of the sodium channel Nav 1.8 results in stimulus-dependent deficits in the dorsal horn neuronal coding to mechanical, but not thermal stimuli applied to the neuronal peripheral receptive field. This implies that Nav 1.8 is either responsible for, or associated with proteins involved in mechanosensation.

The Fourier-Kelvin Stellar Interferometer (FKSI) Nulling Testbed II: Closed-loop Path Length Metrology And Control Subsystem

Science.gov (United States)

Frey, B. J.; Barry, R. K.; Danchi, W. C.; Hyde, T. T.; Lee, K. Y.; Martino, A. J.; Zuray, M. S.

2006-01-01

The Fourier-Kelvin Stellar Interferometer (FKSI) is a mission concept for an imaging and nulling interferometer in the near to mid-infrared spectral region (3-8 microns), and will be a scientific and technological pathfinder for upcoming missions including TPF-I/DARWIN, SPECS, and SPIRIT. At NASA's Goddard Space Flight Center, we have constructed a symmetric Mach-Zehnder nulling testbed to demonstrate techniques and algorithms that can be used to establish and maintain the 10(exp 4) null depth that will be required for such a mission. Among the challenges inherent in such a system is the ability to acquire and track the null fringe to the desired depth for timescales on the order of hours in a laboratory environment. In addition, it is desirable to achieve this stability without using conventional dithering techniques. We describe recent testbed metrology and control system developments necessary to achieve these goals and present our preliminary results.

Local differential geometry of null curves in conformally flat space-time

International Nuclear Information System (INIS)

Urbantke, H.

1989-01-01

The conformally invariant differential geometry of null curves in conformally flat space-times is given, using the six-vector formalism which has generalizations to higher dimensions. This is then paralleled by a twistor description, with a twofold merit: firstly, sometimes the description is easier in twistor terms, sometimes in six-vector terms, which leads to a mutual enlightenment of both; and secondly, the case of null curves in timelike pseudospheres or 2+1 Minkowski space we were only able to treat twistorially, making use of an invariant differential found by Fubini and Cech. The result is the expected one: apart from stated exceptional cases there is a conformally invariant parameter and two conformally invariant curvatures which, when specified in terms of this parameter, serve to characterize the curve up to conformal transformations. 12 refs. (Author)

Time asymmetric spacetimes near null and spatial infinity: I. Expansions of developments of conformally flat data

International Nuclear Information System (INIS)

Kroon, Juan Antonio Valiente

2004-01-01

The conformal Einstein equations and the representation of spatial infinity as a cylinder introduced by Friedrich are used to analyse the behaviour of the gravitational field near null and spatial infinity for the development of data which are asymptotically Euclidean, conformally flat and time asymmetric. Our analysis allows for initial data whose second fundamental form is more general than the one given by the standard Bowen-York ansatz. The conformal Einstein equations imply, upon evaluation on the cylinder at spatial infinity, a hierarchy of transport equations which can be used to calculate asymptotic expansions for the gravitational field in a recursive way. It is found that the solutions to these transport equations develop logarithmic divergences at the critical sets where null infinity meets spatial infinity. Associated with these, there is a series of quantities expressible in terms of the initial data (obstructions), which if zero, preclude the appearance of some of the logarithmic divergences. The obstructions are, in general, time asymmetric. That is, the obstructions at the intersection of future null infinity with spatial infinity are in general different from those obtained at the intersection of past null infinity with spatial infinity. The latter allows for the possibility of having spacetimes where future and past null infinity have different degrees of smoothness. Finally, it is shown that if both sets of obstructions vanish up to a certain order, then the initial data have to be asymptotically Schwarzschildean in a certain sense

Geometry of extended null supersymmetry in M theory

International Nuclear Information System (INIS)

Conamhna, Oisin A.P. Mac

2006-01-01

For supersymmetric spacetimes in 11 dimensions admitting a null Killing spinor, a set of explicit necessary and sufficient conditions for the existence of any number of arbitrary additional Killing spinors is derived. The necessary and sufficient conditions are comprised of algebraic relationships, linear in the spinorial components, between the spinorial components and their first derivatives, and the components of the spin connection and four-form. The integrability conditions for the Killing spinor equation are also analyzed in detail, to determine which components of the field equations are implied by arbitrary additional supersymmetries and the four-form Bianchi identity. This provides a complete formalism for the systematic and exhaustive investigation of all spacetimes with extended null supersymmetry in 11 dimensions. The formalism is employed to show that the general bosonic solution of 11 dimensional supergravity admitting a G 2 structure defined by four Killing spinors is either locally the direct product of R 1,3 with a seven-manifold of G 2 holonomy, or locally the Freund-Rubin direct product of AdS 4 with a seven-manifold of weak G 2 holonomy. In addition, all supersymmetric spacetimes admitting a (G 2 xR 7 )xR 2 structure are classified

Vacuum solutions admitting a geodesic null congruence with shear proportional to expansion

International Nuclear Information System (INIS)

Kupeli, A.H.

1988-01-01

Algebraically general, nontwisting solutions for the vacuum to vacuum generalized Kerr--Schild (GKS) transformation are obtained. These solutions admit a geodesic null congruence with shear proportional to expansion. In the Newman--Penrose formalism, if l/sup μ/ is chosen to be the null vector of the GKS transformation, this property is stated as σ = arho and Da = 0. It is assumed that a is a constant, and the background is chosen as a pp-wave solution. For generic values of a, the GKS metrics consist of the Kasner solutions. For a = +- (1 +- (2)/sup 1/2/), there are solutions with less symmetries including special cases of the Kota--Perjes and Lukacs solutions

Euclidean null controllability of linear systems with delays in state ...

African Journals Online (AJOL)

Sufficient conditions are developed for the Euclidean controllability of linear systems with delay in state and in control. Namely, if the uncontrolled system is uniformly asymptotically stable and the control equation proper, then the control system is Euclidean null controllable. Journal of the Nigerian Association of ...

A comment on the null geodesic equations in Schwarzschild geometry

International Nuclear Information System (INIS)

Rosa, M.A.F.; Rodrigues Junior, W.A.

1986-01-01

An integration of the null geodesic equations in the Schwarzschild geometry, which is valid to first order in GM/Rc 2 is presented. The solution is compared with others published in the literature and their range of validity is analysed. Some misunderstandings are also clarified. (Author) [pt

Argonaute-2-null embryonic stem cells are retarded in self-renewal ...

Indian Academy of Sciences (India)

Present address: Institute of Stem Cells and Regenerative Medicine, Bangalore, India ... [Chandra Shekar P, Naim A, Partha Sarathi D and Kumar S 2011 Argonaute-2-null embryonic stem cells are retarded in self-renewal ..... Research, India.

Telescopes in Near Space: Balloon Exoplanet Nulling Interferometer (BigBENI)

Science.gov (United States)

Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Mauk, Robin

2012-01-01

A significant and often overlooked path to advancing both science and technology for direct imaging and spectroscopic characterization of exosolar planets is to fly "near space" missions, i.e. balloon borne exosolar missions. A near space balloon mission with two or more telescopes, coherently combined, is capable of achieving a subset of the mission science goals of a single large space telescope at a small fraction of the cost. Additionally such an approach advances technologies toward flight readiness for space flight. Herein we discuss the feasibility of flying two 1.2 meter telescopes, with a baseline separation of 3.6 meters, operating in visible light, on a composite boom structure coupled to a modified visible nulling coronagraph operating to achieve an inner working angle of 60 milli-arcseconds. We discuss the potential science return, atmospheric residuals at 135,000 feet, pointing control and visible nulling and evaluate the state-or-art of these technologies with regards to balloon missions.

The null-event method in computer simulation

International Nuclear Information System (INIS)

Lin, S.L.

1978-01-01

The simulation of collisions of ions moving under the influence of an external field through a neutral gas to non-zero temperatures is discussed as an example of computer models of processes in which a probe particle undergoes a series of interactions with an ensemble of other particles, such that the frequency and outcome of the events depends on internal properties of the second particles. The introduction of null events removes the need for much complicated algebra, leads to a more efficient simulation and reduces the likelihood of logical error. (Auth.)

Isolation of two independent allyl alcohol resistant Adh-1 null mutants following selection of pollen and seeds.

NARCIS (Netherlands)

Wisman, E.; Ramanna, M.S.; Zabel, P.

1993-01-01

The Adh-1 null mutant (B15-1-8) isolated previously was used to establish conditions that allow the selection of ADH-deficient pollen grains and seeds of tomato. New Adh-1 null mutants were then selected among the progenies derived from crosses between the genetically unstable tomato lines Yvms,

Cell therapy of congenital corneal diseases with umbilical mesenchymal stem cells: lumican null mice.

Directory of Open Access Journals (Sweden)

Hongshan Liu

Full Text Available BACKGROUND: Keratoplasty is the most effective treatment for corneal blindness, but suboptimal medical conditions and lack of qualified medical personnel and donated cornea often prevent the performance of corneal transplantation in developing countries. Our study aims to develop alternative treatment regimens for congenital corneal diseases of genetic mutation. METHODOLOGY/PRINCIPAL FINDINGS: Human mesenchymal stem cells isolated from neonatal umbilical cords were transplanted to treat thin and cloudy corneas of lumican null mice. Transplantation of umbilical mesenchymal stem cells significantly improved corneal transparency and increased stromal thickness of lumican null mice, but human umbilical hematopoietic stem cells failed to do the same. Further studies revealed that collagen lamellae were re-organized in corneal stroma of lumican null mice after mesenchymal stem cell transplantation. Transplanted umbilical mesenchymal stem cells survived in the mouse corneal stroma for more than 3 months with little or no graft rejection. In addition, these cells assumed a keratocyte phenotype, e.g., dendritic morphology, quiescence, expression of keratocyte unique keratan sulfated keratocan and lumican, and CD34. Moreover, umbilical mesenchymal stem cell transplantation improved host keratocyte functions, which was verified by enhanced expression of keratocan and aldehyde dehydrogenase class 3A1 in lumican null mice. CONCLUSIONS/SIGNIFICANCE: Umbilical mesenchymal stem cell transplantation is a promising treatment for congenital corneal diseases involving keratocyte dysfunction. Unlike donated corneas, umbilical mesenchymal stem cells are easily isolated, expanded, stored, and can be quickly recovered from liquid nitrogen when a patient is in urgent need.

Likelihood of Null Effects of Large NHLBI Clinical Trials Has Increased over Time.

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Robert M Kaplan

Full Text Available We explore whether the number of null results in large National Heart Lung, and Blood Institute (NHLBI funded trials has increased over time.We identified all large NHLBI supported RCTs between 1970 and 2012 evaluating drugs or dietary supplements for the treatment or prevention of cardiovascular disease. Trials were included if direct costs >$500,000/year, participants were adult humans, and the primary outcome was cardiovascular risk, disease or death. The 55 trials meeting these criteria were coded for whether they were published prior to or after the year 2000, whether they registered in clinicaltrials.gov prior to publication, used active or placebo comparator, and whether or not the trial had industry co-sponsorship. We tabulated whether the study reported a positive, negative, or null result on the primary outcome variable and for total mortality.17 of 30 studies (57% published prior to 2000 showed a significant benefit of intervention on the primary outcome in comparison to only 2 among the 25 (8% trials published after 2000 (χ2=12.2,df= 1, p=0.0005. There has been no change in the proportion of trials that compared treatment to placebo versus active comparator. Industry co-sponsorship was unrelated to the probability of reporting a significant benefit. Pre-registration in clinical trials.gov was strongly associated with the trend toward null findings.The number NHLBI trials reporting positive results declined after the year 2000. Prospective declaration of outcomes in RCTs, and the adoption of transparent reporting standards, as required by clinicaltrials.gov, may have contributed to the trend toward null findings.

Inhibition of urethane-induced genotoxicity and cell proliferation in CYP2E1-null mice

International Nuclear Information System (INIS)

Hoffler, Undi; Dixon, Darlene; Peddada, Shyamal; Ghanayem, Burhan I.

2005-01-01

Urethane is a multi-site animal carcinogen and was classified as 'reasonably anticipated to be a human carcinogen.' Urethane is a fermentation by-product and found at appreciable levels in alcoholic beverages and foods such as bread and cheese. Recent work in this laboratory demonstrated for the first time that CYP2E1 is the principal enzyme responsible for urethane metabolism. The current studies were undertaken to assess the relationships between CYP2E1-mediated metabolism and urethane-induced genotoxicity and cell proliferation as determined by induction of micronucleated erythrocytes (MN) and expression of Ki-67, respectively, using CYP2E1-null and wild-type mice. Urethane was administered at 0 (vehicle), 1, 10, or 100 mg/kg/day (p.o.), 5 days/week for 6 weeks. A significant dose-dependent increase in MN was observed in wild-type mice; however, a slight increase was measured in the MN-polychromatic erythrocytes in CYP2E1-null mice treated with 100 mg/kg. A significant increase in the expression of Ki-67 was detected in the livers and the lungs (terminal bronchioles, alveoli, and bronchi) of wild-type mice administered 100 mg urethane/kg in comparison to controls. In contrast, CYP2E1-null mice administered this dose exhibited negligible alterations in Ki-67 expression in the livers and lungs compared to controls. Interestingly, while Ki-67 expression in the forestomach decreased in wild-type mice, it increased in CYP2E1-null mice. Subsequent comparative metabolism studies demonstrated that total urethane-derived radioactivity in the plasma, liver, and lung was significantly higher in CYP2E1-null versus wild-type mice and un-metabolized urethane constituted greater than 83% of the radioactivity in CYP2E1-null mice. Un-metabolized urethane was not detectable in the plasma, liver, and lung of wild-type mice. In conclusion, these data demonstrated that CYP2E1-mediated metabolism of urethane, presumably via epoxide formation, is necessary for the induction of

Population estimators or progeny tests: what is the best method to assess null allele frequencies at SSR loci?

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Oddou-Muratorio, S.; Vendramin, G.G.; Buiteveld, J.; Fady, B.

2009-01-01

Nuclear SSRs are notorious for having relatively high frequencies of null alleles, i.e. alleles that fail to amplify and are thus recessive and undetected in heterozygotes. In this paper, we compare two kinds of approaches for estimating null allele frequencies at seven nuclear microsatellite

MAPK signaling pathways and HDAC3 activity are disrupted during differentiation of emerin-null myogenic progenitor cells

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Carol M. Collins

2017-04-01

Full Text Available Mutations in the gene encoding emerin cause Emery–Dreifuss muscular dystrophy (EDMD. Emerin is an integral inner nuclear membrane protein and a component of the nuclear lamina. EDMD is characterized by skeletal muscle wasting, cardiac conduction defects and tendon contractures. The failure to regenerate skeletal muscle is predicted to contribute to the skeletal muscle pathology of EDMD. We hypothesize that muscle regeneration defects are caused by impaired muscle stem cell differentiation. Myogenic progenitors derived from emerin-null mice were used to confirm their impaired differentiation and analyze selected myogenic molecular pathways. Emerin-null progenitors were delayed in their cell cycle exit, had decreased myosin heavy chain (MyHC expression and formed fewer myotubes. Emerin binds to and activates histone deacetylase 3 (HDAC3. Here, we show that theophylline, an HDAC3-specific activator, improved myotube formation in emerin-null cells. Addition of the HDAC3-specific inhibitor RGFP966 blocked myotube formation and MyHC expression in wild-type and emerin-null myogenic progenitors, but did not affect cell cycle exit. Downregulation of emerin was previously shown to affect the p38 MAPK and ERK/MAPK pathways in C2C12 myoblast differentiation. Using a pure population of myogenic progenitors completely lacking emerin expression, we show that these pathways are also disrupted. ERK inhibition improved MyHC expression in emerin-null cells, but failed to rescue myotube formation or cell cycle exit. Inhibition of p38 MAPK prevented differentiation in both wild-type and emerin-null progenitors. These results show that each of these molecular pathways specifically regulates a particular stage of myogenic differentiation in an emerin-dependent manner. Thus, pharmacological targeting of multiple pathways acting at specific differentiation stages may be a better therapeutic approach in the future to rescue muscle regeneration in vivo.

GST M1-T1 null allele frequency patterns in geographically assorted human populations: a phylogenetic approach.

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Senthilkumar Pitchalu Kasthurinaidu

Full Text Available Genetic diversity in drug metabolism and disposition is mainly considered as the outcome of the inter-individual genetic variation in polymorphism of drug-xenobiotic metabolizing enzyme (XME. Among the XMEs, glutathione-S-transferases (GST gene loci are an important candidate for the investigation of diversity in allele frequency, as the deletion mutations in GST M1 and T1 genotypes are associated with various cancers and genetic disorders of all major Population Affiliations (PAs. Therefore, the present population based phylogenetic study was focused to uncover the frequency distribution pattern in GST M1 and T1 null genotypes among 45 Geographically Assorted Human Populations (GAHPs. The frequency distribution pattern for GST M1 and T1 null alleles have been detected in this study using the data derived from literatures representing 44 populations affiliated to Africa, Asia, Europe, South America and the genome of PA from Gujarat, a region in western India. Allele frequency counting for Gujarat PA and scattered plot analysis for geographical distribution among the PAs were performed in SPSS-21. The GST M1 and GST T1 null allele frequencies patterns of the PAs were computed in Seqboot, Gendist program of Phylip software package (3.69 versions and Unweighted Pair Group method with Arithmetic Mean in Mega-6 software. Allele frequencies from South African Xhosa tribe, East African Zimbabwe, East African Ethiopia, North African Egypt, Caucasian, South Asian Afghanistan and South Indian Andhra Pradesh have been identified as the probable seven patterns among the 45 GAHPs investigated in this study for GST M1-T1 null genotypes. The patternized null allele frequencies demonstrated in this study for the first time addresses the missing link in GST M1-T1 null allele frequencies among GAHPs.

The null hypothesis of GSEA, and a novel statistical model for competitive gene set analysis

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Debrabant, Birgit

2017-01-01

MOTIVATION: Competitive gene set analysis intends to assess whether a specific set of genes is more associated with a trait than the remaining genes. However, the statistical models assumed to date to underly these methods do not enable a clear cut formulation of the competitive null hypothesis....... This is a major handicap to the interpretation of results obtained from a gene set analysis. RESULTS: This work presents a hierarchical statistical model based on the notion of dependence measures, which overcomes this problem. The two levels of the model naturally reflect the modular structure of many gene set...... analysis methods. We apply the model to show that the popular GSEA method, which recently has been claimed to test the self-contained null hypothesis, actually tests the competitive null if the weight parameter is zero. However, for this result to hold strictly, the choice of the dependence measures...

A few insights into the nature of classical and quantum gravity via null-strut calculus

International Nuclear Information System (INIS)

Kheyfets, Arkady

1989-01-01

Null-strut calculus is a 3 + 1 formulation of standard Regge calculus, wherein the dynamics of 3-geometry is propagated in time along light rays, or 'null struts'. However, just as Regge calculus is a discrete and geometric tool for the description of Einstein's theory of gravitation, so too NSC offers itself as a discrete and geometric tool for the description of Einstein's spacetime as the dynamics of discrete spacelike 3-geometries in time, or discrete geometrodynamics. It has for its objectives to provide a discrete model of a 3 + 1 split of spacetime into space plus time, while in so doing to preserve and illuminate the geometric content of Einstein's theory of gravity. The feature of 'light-cone-produced duality' is central to null-strut calculus. This paper will capitalise on this feature, and will attempt to provide some insights into the nature of classical and quantum gravity. (Author)

Null geodesics and wave front singularities in the Gödel space-time

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Kling, Thomas P.; Roebuck, Kevin; Grotzke, Eric

2018-01-01

We explore wave fronts of null geodesics in the Gödel metric emitted from point sources both at, and away from, the origin. For constant time wave fronts emitted by sources away from the origin, we find cusp ridges as well as blue sky metamorphoses where spatially disconnected portions of the wave front appear, connect to the main wave front, and then later break free and vanish. These blue sky metamorphoses in the constant time wave fronts highlight the non-causal features of the Gödel metric. We introduce a concept of physical distance along the null geodesics, and show that for wave fronts of constant physical distance, the reorganization of the points making up the wave front leads to the removal of cusp ridges.

Kinetic modeling of particle acceleration in a solar null point reconnection region

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Baumann, Gisela; Haugbølle, Troels; Nordlund, Åke

2013-01-01

The primary focus of this paper is on the particle acceleration mechanism in solar coronal 3D reconnection null-point regions. Starting from a potential field extrapolation of a SOHO magnetogram taken on 2002 November 16, we first performed MHD simulations with horizontal motions observed by SOHO...... particles and 3.5 billion grid cells of size 17.5\\,km --- these simulations offer a new opportunity to study particle acceleration in solar-like settings....... applied to the photospheric boundary of the computational box. After a build-up of electric current in the fan-plane of the null-point, a sub-section of the evolved MHD data was used as initial and boundary conditions for a kinetic particle-in-cell model of the plasma. We find that sub...

On the null distribution of Bayes factors in linear regression

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We show that under the null, the 2 log (Bayes factor) is asymptotically distributed as a weighted sum of chi-squared random variables with a shifted mean. This claim holds for Bayesian multi-linear regression with a family of conjugate priors, namely, the normal-inverse-gamma prior, the g-prior, and...

No actual measurement … was required: Maxwell and Cavendish's null method for the inverse square law of electrostatics.

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Falconer, Isobel

In 1877 James Clerk Maxwell and his student Donald MacAlister refined Henry Cavendish's 1773 null experiment demonstrating the absence of electricity inside a charged conductor. This null result was a mathematical prediction of the inverse square law of electrostatics, and both Cavendish and Maxwell took the experiment as verifying the law. However, Maxwell had already expressed absolute conviction in the law, based on results of Michael Faraday's. So, what was the value to him of repeating Cavendish's experiment? After assessing whether the law was as secure as he claimed, this paper explores its central importance to the electrical programme that Maxwell was pursuing. It traces the historical and conceptual re-orderings through which Maxwell established the law by constructing a tradition of null tests and asserting the superior accuracy of the method. Maxwell drew on his developing 'doctrine of method' to identify Cavendish's experiment as a member of a wider class of null methods. By doing so, he appealed to the null practices of telegraph engineers, diverted attention from the flawed logic of the method, and sought to localise issues around the mapping of numbers onto instrumental indications, on the grounds that 'no actual measurement … was required'. Copyright © 2017 Elsevier Ltd. All rights reserved.

Null half-supersymmetric solutions in five-dimensional supergravity

International Nuclear Information System (INIS)

Grover, Jai; Gutowski, Jan B.; Sabra, Wafic

2008-01-01

We classify half-supersymmetric solutions of gauged N = 2, D = 5 supergravity coupled to an arbitrary number of abelian vector multiplets for which all of the Killing spinors generate null Killing vectors. We show that there are four classes of solutions, and in each class we find the metric, scalars and gauge field strengths. When the scalar manifold is symmetric, the solutions correspond to a class of local near horizon geometries recently found by Kunduri and Lucietti.

Expression of extracellular matrix components is disrupted in the immature and adult estrogen receptor β-null mouse ovary.

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Alexandra Zalewski

Full Text Available Within the ovary, Estrogen Receptor β (ERβ is localized to the granulosa cells of growing follicles. 17β-estradiol (E2 acting via ERβ augments the actions of follicle stimulating hormone in granulosa cells, leading to granulosa cell differentiation and formation of a preovulatory follicle. Adult ERβ-null females are subfertile and possess ovaries with reduced numbers of growing follicles and corpora lutea. Because the majority of E2 production by granulosa cells occurs once puberty is reached, a role for ERβ in the ovary prior to puberty has not been well examined. We now provide evidence that lack of ERβ disrupts gene expression as early as post-natal day (PND 13, and in particular, we identify a number of genes of the extracellular matrix (ECM that are significantly higher in ERβ-null follicles than in wildtype (WT follicles. Considerable changes occur to the ECM occur during normal folliculogenesis to allow for the dramatic growth, cellular differentiation, and reorganization of the follicle from the primary to preovulatory stage. Using quantitative PCR and immunofluorescence, we now show that several ECM genes are aberrantly overexpressed in ERβ-null follicles. We find that Collagen11a1, a protein highly expressed in cartilage, is significantly higher in ERβ-null follicles than WT follicles as early as PND 13, and this heightened expression continues through PND 23-29 into adulthood. Similarly, Nidogen 2, a highly conserved basement membrane glycoprotein, is elevated in ERβ-null follicles at PND 13 into adulthood, and is elevated specifically in the ERβ-null focimatrix, a basal lamina-like matrix located between granulosa cells. Focimatrix laminin and Collagen IV expression were also higher in ERβ-null ovaries than in WT ovaries at various ages. Our findings suggest two novel observations: a that ERβ regulates granulosa cell gene expression ovary prior to puberty, and b that ERβ regulates expression of ECM components in the

Hamilton-Jacobi formalism for Podolsky's electromagnetic theory on the null-plane

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Bertin, M. C.; Pimentel, B. M.; Valcárcel, C. E.; Zambrano, G. E. R.

2017-08-01

We develop the Hamilton-Jacobi formalism for Podolsky's electromagnetic theory on the null-plane. The main goal is to build the complete set of Hamiltonian generators of the system as well as to study the canonical and gauge transformations of the theory.

Spinal cord compression injury in lysophosphatidic acid 1 receptor-null mice promotes maladaptive pronociceptive descending control.

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Suardíaz, M; Galan-Arriero, I; Avila-Martin, G; Estivill-Torrús, G; de Fonseca, F R; Chun, J; Gómez-Soriano, J; Bravo-Esteban, E; Taylor, J

2016-02-01

Although activation of the lysophosphatidic acid receptor 1 (LPA1) is known to mediate pronociceptive effects in peripheral pain models, the role of this receptor in the modulation of spinal nociception following spinal cord injury (SCI) is unknown. In this study, LPA1 regulation of spinal excitability mediated by supraspinal descending antinociceptive control systems was assessed following SCI in both wild-type (WT) and maLPA1-null receptor mice. The effect of a T8 spinal compression in WT and maLPA1-null mice was assessed up to 1 month after SCI using histological, immunohistochemical and behavioural techniques analysis including electrophysiological recording of noxious toes-Tibialis Anterior (TA) stimulus-response reflex activity. The effect of a T3 paraspinal transcutaneous electrical conditioning stimulus on TA noxious reflex temporal summation was also assessed. Histological analysis demonstrated greater dorsolateral funiculus damage after SCI in maLPA1-null mice, without a change in the stimulus-response function of the TA noxious reflex when compared to WT mice. While T3 conditioning stimulation in the WT group inhibited noxious TA reflex temporal summation after SCI, this stimulus strongly excited TA reflex temporal summation in maLPA1-null mice. The functional switch from descending inhibition to maladaptive facilitation of central excitability of spinal nociception demonstrated in maLPA1-null mice after SCI was unrelated to a general change in reflex activity. These data suggest that the LPA1 receptor is necessary for inhibition of temporal summation of noxious reflex activity, partly mediated via long-tract descending modulatory systems acting at the spinal level. © 2015 European Pain Federation - EFIC®

Numerical simulations of sheared magnetic lines at the solar null line

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Kuźma, B.; Murawski, K.; Solov'ev, A.

2015-05-01

Aims: We perform numerical simulations of sheared magnetic lines at the magnetic null line configuration of two magnetic arcades that are settled in a gravitationally stratified and magnetically confined solar corona. Methods: We developed a general analytical model of a 2.5D solar atmospheric structure. As a particular application of this model, we adopted it for the curved magnetic field lines with an inverted Y shape that compose the null line above two magnetic arcades, which are embedded in the solar atmosphere that is specified by the realistic temperature distribution. The physical system is described by 2.5D magnetohydrodynamic equations that are numerically solved by the FLASH code. Results: The magnetic field line shearing, implemented about 200 km below the transition region, results in Alfvén and magnetoacoustic waves that are able to penetrate solar coronal regions above the magnetic null line. As a result of the coupling of these waves, partial reflection from the transition region and scattering from inhomogeneous regions the Alfvén waves experience fast attenuation on time scales comparable to their wave periods, and the physical system relaxes in time. The attenuation time grows with the large amplitude and characteristic growing time of the shearing. Conclusions: By having chosen a different magnetic flux function, the analytical model we devised can be adopted to derive equilibrium conditions for a diversity of 2.5D magnetic structures in the solar atmosphere. Movie associated to Fig. 5 is available in electronic form at http://www.aanda.org

Pituitary null cell adenoma in a domestic llama (Lama glama).

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Chalkley, M D; Kiupel, M; Draper, A C E

2014-07-01

Pituitary gland neoplasia has been reported rarely in camelids. A 12-year-old neutered male llama (Lama glama) presented with lethargy, inappetence and neurological signs. On physical examination, the llama was mentally dull and exhibited compulsive pacing and circling to the left. Complete blood count and serum biochemistry revealed haemoconcentration, mild hypophosphataemia, hyperglycaemia, hypercreatininaemia and hyperalbuminaemia. Humane destruction was elected due to rapid clinical deterioration and poor prognosis. Post-mortem examination revealed a pituitary macroadenoma and bilateral internal hydrocephalus. Microscopically, the pituitary tumour was composed of neoplastic chromophobic pituitary cells. Ultrastructural studies revealed similar neoplastic cells to those previously described in human null cell adenomas. Immunohistochemically, the neoplastic cells were strongly immunoreactive for neuroendocrine markers (synaptophysin and chromogranin A), but did not exhibit immunoreactivity for epithelial, mesenchymal, neuronal and all major pituitary hormone markers (adrenocorticotropic hormone, follicle stimulating hormone, growth hormone, luteinizing hormone, melanocyte-stimulating hormone, prolactin and thyroid stimulating hormone), consistent with the diagnosis of a pituitary null cell adenoma. This is the first report of pituitary neoplasia in a llama. Copyright © 2014 Elsevier Ltd. All rights reserved.

Identifying the null subject: evidence from event-related brain potentials.

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Demestre, J; Meltzer, S; García-Albea, J E; Vigil, A

1999-05-01

Event-related brain potentials (ERPs) were recorded during spoken language comprehension to study the on-line effects of gender agreement violations in controlled infinitival complements. Spanish sentences were constructed in which the complement clause contained a predicate adjective marked for syntactic gender. By manipulating the gender of the antecedent (i.e., the controller) of the implicit subject while holding constant the gender of the adjective, pairs of grammatical and ungrammatical sentences were created. The detection of such a gender agreement violation would indicate that the parser had established the coreference relation between the null subject and its antecedent. The results showed a complex biphasic ERP (i.e., an early negativity with prominence at anterior and central sites, followed by a centroparietal positivity) in the violating condition as compared to the non-violating conditions. The brain reacts to NP-adjective gender agreement violations within a few hundred milliseconds of their occurrence. The data imply that the parser has properly coindexed the null subject of an infinitive clause with its antecedent.

Modelling the electromechanical interactions in a null-flux EDS Maglev system

NARCIS (Netherlands)

Boeij, de J.; Steinbuch, M.; Gutierrez, H.M.; Fair, H.D.

2004-01-01

The fundamental electromechanical interactionsin a passive null-ux EDS maglev system aremediated by the voltages induced in the levita-tion coils by the sled magnets, and by the forcesexerted on the sled as a result of the inducedcurrents. This paper presents a reliable andcompact method to

What Constitutes Science and Scientific Evidence: Roles of Null Hypothesis Testing

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Chang, Mark

2017-01-01

We briefly discuss the philosophical basis of science, causality, and scientific evidence, by introducing the hidden but most fundamental principle of science: the similarity principle. The principle's use in scientific discovery is illustrated with Simpson's paradox and other examples. In discussing the value of null hypothesis statistical…

Expression patterns of the aquaporin gene family during renal development: influence of genetic variability.

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Parreira, Kleber S; Debaix, Huguette; Cnops, Yvette; Geffers, Lars; Devuyst, Olivier

2009-08-01

High-throughput analyses have shown that aquaporins (AQPs) belong to a cluster of genes that are differentially expressed during kidney organogenesis. However, the spatiotemporal expression patterns of the AQP gene family during tubular maturation and the potential influence of genetic variation on these patterns and on water handling remain unknown. We investigated the expression patterns of all AQP isoforms in fetal (E13.5 to E18.5), postnatal (P1 to P28), and adult (9 weeks) kidneys of inbred (C57BL/6J) and outbred (CD-1) mice. Using quantitative polymerase chain reaction (PCR), we evidenced two mRNA patterns during tubular maturation in C57 mice. The AQPs 1-7-11 showed an early (from E14.5) and progressive increase to adult levels, similar to the mRNA pattern observed for proximal tubule markers (Megalin, NaPi-IIa, OAT1) and reflecting the continuous increase in renal cortical structures during development. By contrast, AQPs 2-3-4 showed a later (E15.5) and more abrupt increase, with transient postnatal overexpression. Most AQP genes were expressed earlier and/or stronger in maturing CD-1 kidneys. Furthermore, adult CD-1 kidneys expressed more AQP2 in the collecting ducts, which was reflected by a significant delay in excreting a water load. The expression patterns of proximal vs. distal AQPs and the earlier expression in the CD-1 strain were confirmed by immunoblotting and immunostaining. These data (1) substantiate the clustering of important genes during tubular maturation and (2) demonstrate that genetic variability influences the regulation of the AQP gene family during tubular maturation and water handling by the mature kidney.

Frequency of null allele of Human Leukocyte Antigen-G (HLA-G locus in subjects to recurrent miscarriage

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Nazila Alizadeh

2016-07-01

Full Text Available Background: Human leukocyte antigen-G (HLA-G is a non-classical class I molecule highly expressed by extravillous cytotrophoblast cells. Due to a single base pair deletion, its function can be compensated by other isoforms. Investigating the frequency of null allele in Recurrent Miscarriage (RM subjects could be useful in understanding the relationship between frequency of this allele and RM in a given population. Objective: This study aimed to determine the frequency of HLA-G*0105N null allele and its potential association with down-regulation of HLA-G in subjects with RM. Materials and Methods: Western blotting was used to assess the level of HLA-G protein expression. For investigating the frequency of HLA-G*0105N null allele in RM subjects, PCR-RFLP method was used. Exon 3 of HLA-G gene was amplified by polymerase chain reaction (PCR. Subsequently, PpuM-1 enzyme was employed to digest the PCR products and fragments were analyzed using gel electrophoresis. Results: Digestion using restriction enzyme showed the presence of heterozygous HLA-G*0105N null allele in 10% of the test population. Western blotting results confirmed the decrease in expression of HLA-G in the placental tissue of subjects with RM compared to subjects who could give normal birth. Conclusion: The frequency of heterozygous HLA-G*0105N null allele was high to some extent in subjects with RM. The mutation rate in subjects suggested that there is a significant association between RM and frequency of mutations in this allele.

Frequency of null allele of Human Leukocyte Antigen-G (HLA-G) locus in subjects to recurrent miscarriage

Science.gov (United States)

Alizadeh, Nazila; Mosaferi, Elnaz; Farzadi, Laya; Majidi, Jafar; Monfaredan, Amir; Yousefi, Bahman; Baradaran, Behzad

2016-01-01

Background: Human leukocyte antigen-G (HLA-G) is a non-classical class I molecule highly expressed by extravillous cytotrophoblast cells. Due to a single base pair deletion, its function can be compensated by other isoforms. Investigating the frequency of null allele in Recurrent Miscarriage (RM) subjects could be useful in understanding the relationship between frequency of this allele and RM in a given population. Objective: This study aimed to determine the frequency of HLA-G*0105N null allele and its potential association with down-regulation of HLA-G in subjects with RM. Materials and Methods: Western blotting was used to assess the level of HLA-G protein expression. For investigating the frequency of HLA-G*0105N null allele in RM subjects, PCR-RFLP method was used. Exon 3 of HLA-G gene was amplified by polymerase chain reaction (PCR). Subsequently, PpuM-1 enzyme was employed to digest the PCR products and fragments were analyzed using gel electrophoresis. Results: Digestion using restriction enzyme showed the presence of heterozygous HLA-G*0105N null allele in 10% of the test population. Western blotting results confirmed the decrease in expression of HLA-G in the placental tissue of subjects with RM compared to subjects who could give normal birth. Conclusion: The frequency of heterozygous HLA-G*0105N null allele was high to some extent in subjects with RM. The mutation rate in subjects suggested that there is a significant association between RM and frequency of mutations in this allele. PMID:27525330

Conformal gravity, the Einstein equations and spaces of complex null geodesics

Energy Technology Data Exchange (ETDEWEB)

Baston, R.J.; Mason, L.J.

1987-07-01

The aim of the paper is to give a twistorial characterisation of the field equations of conformal gravity and of Einstein spacetimes. Strong evidence is provided for a particularly concise characterisation of these equations in terms of 'formal neighbourhoods'of the space of complex null geodesics. Second-order perturbations of the metric of complexified Minkowski space are considered. These correspond to certain infinitesimal deformations of its space of complex null geodesics, PN. PN has a natural codimension one embedding into a larger space. It is shown that deformations extend automatically to the fourth-order embedding (that is, the fourth formal neighbourhood). They extend to the fifth formal neighbourhood if and only if the corresponding perturbation in the metric has vanishing Bach tensor. Finally, deformations which extend to the sixth formal neighbourhood correspond to perturbations in the metric that are conformally related to ones satisfying the Einstein equations. The authors present arguments which suggest that the results will also hold when spacetime is fully curved.

Conformal gravity, the Einstein equations and spaces of complex null geodesics

International Nuclear Information System (INIS)

Baston, R.J.; Mason, L.J.

1987-01-01

The aim of the paper is to give a twistorial characterisation of the field equations of conformal gravity and of Einstein spacetimes. Strong evidence is provided for a particularly concise characterisation of these equations in terms of 'formal neighbourhoods'of the space of complex null geodesics. Second-order perturbations of the metric of complexified Minkowski space are considered. These correspond to certain infinitesimal deformations of its space of complex null geodesics, PN. PN has a natural codimension one embedding into a larger space. It is shown that deformations extend automatically to the fourth-order embedding (that is, the fourth formal neighbourhood). They extend to the fifth formal neighbourhood if and only if the corresponding perturbation in the metric has vanishing Bach tensor. Finally, deformations which extend to the sixth formal neighbourhood correspond to perturbations in the metric that are conformally related to ones satisfying the Einstein equations. The authors present arguments which suggest that the results will also hold when spacetime is fully curved. (author)

Canonical theory of spherically symmetric spacetimes with cross-streaming null dusts

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Bičák, Jiří; Hájíček, Petr

2003-11-01

The Hamiltonian dynamics of two-component spherically symmetric null dust is studied with regard to the quantum theory of gravitational collapse. The components—the ingoing and outgoing dusts—are assumed to interact only through gravitation. Different kinds of singularities, naked or “clothed,” which can form during collapse processes are described. The general canonical formulation of the one-component null-dust dynamics by Bičák and Kuchař is restricted to the spherically symmetric case and used to construct an action for the two components. The transformation from a metric variable to the quasilocal mass is shown to simplify the mathematics. The action is reduced by a choice of gauge and the corresponding true Hamiltonian is written down. Asymptotic coordinates and energy densities of dust shells are shown to form a complete set of Dirac observables. The action of the asymptotic time translation on the observables is defined but it has been calculated explicitly only in the case of one-component dust (Vaidya metric).

Randomizing growing networks with a time-respecting null model

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Ren, Zhuo-Ming; Mariani, Manuel Sebastian; Zhang, Yi-Cheng; Medo, Matúš

2018-05-01

Complex networks are often used to represent systems that are not static but grow with time: People make new friendships, new papers are published and refer to the existing ones, and so forth. To assess the statistical significance of measurements made on such networks, we propose a randomization methodology—a time-respecting null model—that preserves both the network's degree sequence and the time evolution of individual nodes' degree values. By preserving the temporal linking patterns of the analyzed system, the proposed model is able to factor out the effect of the system's temporal patterns on its structure. We apply the model to the citation network of Physical Review scholarly papers and the citation network of US movies. The model reveals that the two data sets are strikingly different with respect to their degree-degree correlations, and we discuss the important implications of this finding on the information provided by paradigmatic node centrality metrics such as indegree and Google's PageRank. The randomization methodology proposed here can be used to assess the significance of any structural property in growing networks, which could bring new insights into the problems where null models play a critical role, such as the detection of communities and network motifs.

Non-dissipative electromagnetic media with two Lorentz null cones

International Nuclear Information System (INIS)

Dahl, Matias F.

2013-01-01

We study Maxwell’s equations on a 4-manifold where the electromagnetic medium is modeled by an antisymmetric (2/2 )-tensor with 21 real coefficients. In this setting the Fresnel surface is a fourth-order polynomial surface that describes the dynamical response of the medium in the geometric optics limit. For example, in an isotropic medium the Fresnel surface is a Lorentz null cone. The contribution of this paper is the pointwise description of all electromagnetic medium tensors κ with real coefficients that satisfy the following three conditions: (i)medium κ is invertible, (ii)medium κ is skewon-free, or non-dissipative, (iii)the Fresnel surface of κ is the union of two distinct Lorentz null cones. We show that there are only three classes of media with these properties and give explicit expressions in local coordinates for each class. - Highlights: ► We find two new electromagnetic media classes for which the Fresnel surface decomposes into two light cones. ► In a suitable setting we classify all electromagnetic media where this is the case. ► We find an electromagnetic medium tensor with three different signal speeds in one direction. ► The work is related to [5], which classifies all media with one light cone (in a suitable setting).

Pharmacological blockade of aquaporin-1 water channel by AqB013 restricts migration and invasiveness of colon cancer cells and prevents endothelial tube formation in vitro.

Science.gov (United States)

Dorward, Hilary S; Du, Alice; Bruhn, Maressa A; Wrin, Joseph; Pei, Jinxin V; Evdokiou, Andreas; Price, Timothy J; Yool, Andrea J; Hardingham, Jennifer E

2016-02-24

Aquaporins (AQP) are water channel proteins that enable fluid fluxes across cell membranes, important for homeostasis of the tissue environment and for cell migration. AQP1 knockout mouse models of human cancers showed marked inhibition of tumor-induced angiogenesis, and in pre-clinical studies of colon adenocarcinomas, forced over-expression of AQP1 was shown to increase angiogenesis, invasion and metastasis. We have synthesized small molecule antagonists of AQP1. Our hypothesis is that inhibition of AQP1 will reduce migration and invasiveness of colon cancer cells, and the migration and tube-forming capacity of endothelial cells in vitro. Expression of AQP1 in cell lines was assessed by quantitative (q) PCR, western blot and immunofluorescence, while expression of AQP1 in human colon tumour tissue was assessed by immunohistochemistry. The effect of varying concentrations of the AQP1 inhibitor AqB013 was tested on human colon cancer cell lines expressing high versus low levels of AQP1, using wound closure (migration) assays, matrigel invasion assays, and proliferation assays. The effect of AqB013 on angiogenesis was tested using an endothelial cell tube-formation assay. HT29 colon cancer cells with high AQP1 levels showed significant inhibition of migration compared to vehicle control of 27.9% ± 2.6% (p migration of HCT-116 cells with low AQP1 expression. In an invasion assay, HT29 cells treated with 160 μM of AqB013, showed a 60.3% ± 8.5% decrease in invasion at 144 hours (p < 0.0001) and significantly decreased rate of invasion compared with the vehicle control (F-test, p = 0.001). Almost complete inhibition of endothelial tube formation (angiogenesis assay) was achieved at 80 μM AqB013 compared to vehicle control (p < 0.0001). These data provide good evidence for further testing of the inhibitor as a therapeutic agent in colon cancer.

A Coding of Real Null Four-Momenta into World-Sheet Coordinates

Directory of Open Access Journals (Sweden)

David B. Fairlie

2009-01-01

Full Text Available The results of minimizing the action for string-like systems on a simply connected world sheet are shown to encode the Cartesian components of real null momentum four-vectors into coordinates on the world sheet. This identification arises consistently from different approaches to the problem.

Development of IR single mode optical fibers for DARWIN-nulling interferometry

NARCIS (Netherlands)

Chakkalakkal Abdulla, S.M.; Cheng, L.K.; Bosch, B. van den; Dijkhuizen, N.; Nieuwland, R.A.; Gielesen, W.L.M.; Lucas, J.; Boussard-Plédel, C.; Conseil, C.; Bureau, B.; Carmo, J.P. do

2014-01-01

The DARWIN mission aims to detect weak infra-red emission lines from distant orbiting earth-like planets using nulling interferometry. This requires filtering of wavefront errors using single mode waveguides operating at a wavelength range of 6.5-20 μm. This article describes the optical design of

CD4+CD28null T Cells are related to previous cytomegalovirus infection but not to accelerated atherosclerosis in ANCA-associated vasculitis.

Science.gov (United States)

Slot, Marjan C; Kroon, Abraham A; Damoiseaux, Jan G M C; Theunissen, Ruud; Houben, Alfons J H M; de Leeuw, Peter W; Tervaert, Jan Willem Cohen

2017-05-01

Previous studies have suggested an increased risk for cardiovascular events in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). We analyzed the presence of atherosclerotic damage in patients with AAV in relation to the presence of CD4 + CD28 null T cells and antibodies against cytomegalovirus (CMV) and human Heat-Shock Protein 60 (hHSP60). In this cross-sectional study, patients with inactive AAV were compared with healthy controls (HC). Carotid intima-media thickness (IMT) and aortic pulse-wave velocity (PWV) were measured. In addition, CD4 + CD28 null T cells, anti-CMV, and anti-hHSP60 levels were determined. Forty patients with AAV were included. Patients' spouses were recruited as HC (N = 38). CD4 + CD28 null T cells are present in patients with AAV in a higher percentage (median 3.1, range 0.01-85) than in HC (0.28, 0-36, P CD4 + CD28 null T cells (0.33 vs 13.8, P CD4 + CD28 null T cells and/or a previous CMV infection and IMT or PWV. There was no relation between anti-hHSP60 and CD4 + CD28 null T cells. Increased PWV values suggest atherosclerotic damage in patients with AAV. Plaque size, as determined by IMT, did not differ. CD4 + CD28 null T cells are increased in AAV and related to the previous CMV infection.

Null alleles and sequence variations at primer binding sites of STR loci within multiplex typing systems.

Science.gov (United States)

Yao, Yining; Yang, Qinrui; Shao, Chengchen; Liu, Baonian; Zhou, Yuxiang; Xu, Hongmei; Zhou, Yueqin; Tang, Qiqun; Xie, Jianhui

2018-01-01

Rare variants are widely observed in human genome and sequence variations at primer binding sites might impair the process of PCR amplification resulting in dropouts of alleles, named as null alleles. In this study, 5 cases from routine paternity testing using PowerPlex ® 21 System for STR genotyping were considered to harbor null alleles at TH01, FGA, D5S818, D8S1179, and D16S539, respectively. The dropout of alleles was confirmed by using alternative commercial kits AGCU Expressmarker 22 PCR amplification kit and AmpFℓSTR ® . Identifiler ® Plus Kit, and sequencing results revealed a single base variation at the primer binding site of each STR locus. Results from the collection of previous reports show that null alleles at D5S818 were frequently observed in population detected by two PowerPlex ® typing systems and null alleles at D19S433 were mostly observed in Japanese population detected by two AmpFℓSTR™ typing systems. Furthermore, the most popular mutation type appeared the transition from C to T with G to A, which might have a potential relationship with DNA methylation. Altogether, these results can provide helpful information in forensic practice to the elimination of genotyping discrepancy and the development of primer sets. Copyright © 2017 Elsevier B.V. All rights reserved.

No association of GSTM1 null polymorphism with endometriosis in women from central and southern Iran

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Razieh Dehghani Firouzabadi

2012-01-01

Full Text Available Background: Endometriosis is one of the most common gynecologic disorders. It is a complex trait and both genetic and environmental factors have been implicated in its pathogenesis. There is growing evidence indicating that exposure to environmental contaminants is a risk factor for endometriosis. Glutathione-S-Transferase M1 (GSTM1 is one of the genes involved in detoxification of endogenous and exogenous compounds. Objective: Several studies have indicated an association between GSTM1 null mutation and endometriosis. In this study, the possible association between the GSTM1 gene null genotype and susceptibility to endometriosis in woman from central and southern Iran was investigated.Materials and Methods: One hundred and one unrelated premenopausal women with endometriosis and 142 unrelated healthy premenopausal women without endometriosis were enrolled in the study. Genomic DNA was extracted from Peripheral blood in all subjects. GSTM1 null genotyping was performed by polymerase chain reaction (PCR.Results: There was no significant difference between frequencies of GSTM1 null genotype in case and control groups (50.5% Vs. 52.1%, p=0.804. Furthermore, this genotype was not associated with severity of endometriosis in our sample (p=0.77. Conclusion: further studies involving gene-environment and gene-gene interactions, particularly combination of GSTM1 and other GST gene family polymorphisms are needed.

Do electromagnetic waves always propagate along null geodesics?

International Nuclear Information System (INIS)

Asenjo, Felipe A; Hojman, Sergio A

2017-01-01

We find exact solutions to Maxwell equations written in terms of four-vector potentials in non–rotating, as well as in Gödel and Kerr spacetimes. We show that Maxwell equations can be reduced to two uncoupled second-order differential equations for combinations of the components of the four-vector potential. Exact electromagnetic waves solutions are written on given gravitational field backgrounds where they evolve. We find that in non–rotating spherical symmetric spacetimes, electromagnetic waves travel along null geodesics. However, electromagnetic waves on Gödel and Kerr spacetimes do not exhibit that behavior. (paper)

Null geodesic deviation II. Conformally flat space--times

International Nuclear Information System (INIS)

Peters, P.C.

1975-01-01

The equation of geodesic deviation is solved in conformally flat space--time in a covariant manner. The solution is given as an integral equation for general geodesics. The solution is then used to evaluate second derivatives of the world function and derivatives of the parallel propagator, which need to be known in order to find the Green's function for wave equations in curved space--time. A method of null geodesic limits of two-point functions is discussed, and used to find the scalar Green's function as an iterative series

Circulating CD4+CD28null T Cells May Increase the Risk of an Atherosclerotic Vascular Event Shortly after Kidney Transplantation

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Michiel G. H. Betjes

2013-01-01

Full Text Available Proinflammatory CD4+ T cells without the costimulatory molecule CD28 (CD4+CD28null T cells are expanded in patients with end-stage renal disease (ESRD and associated with atherosclerotic vascular events (AVE. In a prospective study, the number of circulating CD4+CD28null T cells was established in 295 ESRD patients prior to receiving a kidney allograft. Within the first year after transplantation, an AVE occurred in 20 patients. Univariate analysis showed that besides a history of cardiovascular disease (CVDpos, HR 8.1, , age (HR 1.04, , dyslipidaemia (HR 8.8, , and the % of CD4+CD28null T cells (HR 1.04 per % increase, 95% CI 1.00–1.09, were significantly associated with the occurrence of a posttransplantation AVE. In a multivariate analysis, only CVDpos remained a significant risk factor with a significant and positive interaction between the terms CVDpos and the % of CD4+CD28null T cells (HR 1.05, 95% CI 1.03–1.11, . Within the CVDpos group, the incidence of an AVE was 13% in the lowest tertile compared to 25% in the highest tertile of % of CD4+CD28null T cells. In conclusion, the presence of circulating CD4+CD28null T cells is associated with an increased risk for a cardiovascular event shortly after kidney transplantation.

Combined glutathione S transferase M1/T1 null genotypes is associated with type 2 diabetes mellitus

Science.gov (United States)

POROJAN, MIHAI D.; BALA, CORNELIA; ILIES, ROXANA; CATANA, ANDREEA; POPP, RADU A.; DUMITRASCU, DAN L.

2015-01-01

Background Due to new genetic insights, a considerably large number of genes and polymorphic gene variants are screened and linked with the complex pathogenesis of type 2 diabetes (DM). Our study aimed to investigate the association between the two isoforms of the glutathione S-transferase genes (Glutathione S transferase isoemzyme type M1- GSTM1 and Glutathione S transferase isoemzyme type T1-GSTT1) and the prevalence of DM in the Northern Romanian population. Methods We conducted a cross-sectional, randomized, case-control study evaluating the frequency of GSTM1 and GSTT1 null alleles in patients diagnosed with DM. A total of 106 patients diagnosed with DM and 124 healthy controls were included in the study. GSTM1 and GSTT1 null alleles genotyping was carried out using Multiplex PCR amplification of relevant gene fragments, followed by gel electrophoresis analysis of the resulting amplicons. Results Molecular analysis did not reveal an increased frequency of the null GSTM1 and GSTT1 alleles (mutant genotypes) respectively in the DM group compared to controls (p=0.171, OR=1.444 CI=0.852–2.447; p=0.647, OR=0.854, CI=0.436–1.673). Nevertheless, the combined GSTM1/GSTT1 null genotypes were statistically significantly higher in DM patients compared to control subjects (p=0.0021, OR=0.313, CI=0.149–0.655) Conclusions The main finding of our study is that the combined, double GSTM1/GSTT1 null genotypes are to be considered among the polymorphic genetic risk factors for type 2 DM. PMID:26528065

Nulling interferometry for the darwin mission: laboratory demonstration experiment

Science.gov (United States)

Ollivier, Marc; Léger, Alain; Sekulic, Predrag; Labèque, Alain; Michel, Guy

2017-11-01

The DARWIN mission is a project of the European Space Agency that should allow around 2012 the search for extrasolar planets and a spectral analysis of their potential atmosphere in order to evidence gases and particularly tracers of life. The principle of the instrument is based on the Bracewell nulling interferometer. It allows high angular resolution and high dynamic range. However, this concept, proposed more than 20 years ago, has never been experimentally demonstrated in the thermal infrared with high levels of extinction. We present here a laboratory monochromatic experiment dedicated to this goal. A theoretical and numerical approach of the question highlights a strong difficulty: the need for very clean and homogeneous wavefronts, in terms of intensity, phase and polarisation distribution. A classical interferometric approach appears to be insufficient to reach our goals. We have shown theoretically then numerically that this difficulty can be surpassed if we perform an optical filtering of the interfering beams. This technique allows us to decrease strongly the optical requirements and to view very high interferometric contrast measurements with commercial optical pieces. We present here a laboratory interferometer working at 10,6 microns, and implementing several techniques of optical filtering (pinholes and single-mode waveguides), its realisation, and its first promising results. We particularly present measurements that exhibit stable visibility levels better than 99,9% that is to say extinction levels better than 1000.

Exact null distributions of quadratic distribution-free statistics for two-way classification

NARCIS (Netherlands)

Wiel, van de M.A.

2004-01-01

Abstract We present new techniques for computing exact distributions of `Friedman-type¿ statistics. Representing the null distribution by a generating function allows for the use of general, not necessarily integer-valued rank scores. Moreover, we use symmetry properties of the multivariate

The Need for Nuance in the Null Hypothesis Significance Testing Debate

Science.gov (United States)

Häggström, Olle

2017-01-01

Null hypothesis significance testing (NHST) provides an important statistical toolbox, but there are a number of ways in which it is often abused and misinterpreted, with bad consequences for the reliability and progress of science. Parts of contemporary NHST debate, especially in the psychological sciences, is reviewed, and a suggestion is made…

Deficient and Null Variants of SERPINA1 Are Proteotoxic in a Caenorhabditis elegans Model of α1-Antitrypsin Deficiency.

Directory of Open Access Journals (Sweden)

Erin E Cummings

Full Text Available α1-antitrypsin deficiency (ATD predisposes patients to both loss-of-function (emphysema and gain-of-function (liver cirrhosis phenotypes depending on the type of mutation. Although the Z mutation (ATZ is the most prevalent cause of ATD, >120 mutant alleles have been identified. In general, these mutations are classified as deficient (<20% normal plasma levels or null (<1% normal levels alleles. The deficient alleles, like ATZ, misfold in the ER where they accumulate as toxic monomers, oligomers and aggregates. Thus, deficient alleles may predispose to both gain- and loss-of-function phenotypes. Null variants, if translated, typically yield truncated proteins that are efficiently degraded after being transiently retained in the ER. Clinically, null alleles are only associated with the loss-of-function phenotype. We recently developed a C. elegans model of ATD in order to further elucidate the mechanisms of proteotoxicity (gain-of-function phenotype induced by the aggregation-prone deficient allele, ATZ. The goal of this study was to use this C. elegans model to determine whether different types of deficient and null alleles, which differentially affect polymerization and secretion rates, correlated to any extent with proteotoxicity. Animals expressing the deficient alleles, Mmalton, Siiyama and S (ATS, showed overall toxicity comparable to that observed in patients. Interestingly, Siiyama expressing animals had smaller intracellular inclusions than ATZ yet appeared to have a greater negative effect on animal fitness. Surprisingly, the null mutants, although efficiently degraded, showed a relatively mild gain-of-function proteotoxic phenotype. However, since null variant proteins are degraded differently and do not appear to accumulate, their mechanism of proteotoxicity is likely to be different to that of polymerizing, deficient mutants. Taken together, these studies showed that C. elegans is an inexpensive tool to assess the proteotoxicity of

Volume 10 No. 9 September 2010 4016 MICRO LEVEL IMPACT OF ...

African Journals Online (AJOL)

user

2010-09-09

Sep 9, 2010 ... obvious because agriculture remains the mainstay of Nigerian economy, contributing about 40% of the total ... will enable the rural poor to increase their level of production of economic goods as well as their income ..... [since t (cal) > the t (tab) 0.025 = 2.00], it means that the null hypothesis of no significant ...

Observation of a 3D Magnetic Null Point

Energy Technology Data Exchange (ETDEWEB)

Romano, P.; Falco, M. [INAF—Osservatorio Astrofisico di Catania, Via S. Sofia 78, I-95123 Catania (Italy); Guglielmino, S. L.; Murabito, M., E-mail: prom@oact.inaf.it [Dipartimento di Fisica e Astronomia—Sezione Astrofisica, Università di Catania, Via S. Sofia 78, I-95123 Catania (Italy)

2017-03-10

We describe high-resolution observations of a GOES B-class flare characterized by a circular ribbon at the chromospheric level, corresponding to the network at the photospheric level. We interpret the flare as a consequence of a magnetic reconnection event that occurred at a three-dimensional (3D) coronal null point located above the supergranular cell. The potential field extrapolation of the photospheric magnetic field indicates that the circular chromospheric ribbon is cospatial with the fan footpoints, while the ribbons of the inner and outer spines look like compact kernels. We found new interesting observational aspects that need to be explained by models: (1) a loop corresponding to the outer spine became brighter a few minutes before the onset of the flare; (2) the circular ribbon was formed by several adjacent compact kernels characterized by a size of 1″–2″; (3) the kernels with a stronger intensity emission were located at the outer footpoint of the darker filaments, departing radially from the center of the supergranular cell; (4) these kernels started to brighten sequentially in clockwise direction; and (5) the site of the 3D null point and the shape of the outer spine were detected by RHESSI in the low-energy channel between 6.0 and 12.0 keV. Taking into account all these features and the length scales of the magnetic systems involved in the event, we argue that the low intensity of the flare may be ascribed to the low amount of magnetic flux and to its symmetric configuration.

Unique and analogous functions of aquaporin O for fiber cell architecture and ocular lens transparency

Energy Technology Data Exchange (ETDEWEB)

Kumari, S.S.; Eswaramoorthy, S.; Mathias, R. T.; Varadaraj, K.

2011-09-01

Aquaporin (AQP) 1 and AQP0 water channels are expressed in lens epithelial and fiber cells, respectively, facilitating fluid circulation for nourishing the avascular lens to maintain transparency. Even though AQP0 water permeability is 40-fold less than AQP1, AQP0 is selectively expressed in the fibers. Delimited AQP0 fiber expression is attributed to a unique structural role as an adhesion protein. To validate this notion, we determined if wild type (WT) lens ultrastructure and fibercell adhesion are different in AQP0{sup -/-}, and TgAQP1{sup +/+}/AQP0{sup -/-} mice that transgenically express AQP1 (TgAQP1) in fibercells without AQP0 (AQP0{sup -/-}). In WT, lenses were transparent with 'Y' sutures. Fibers contained opposite end curvature, lateral interdigitations, hexagonal shape, and were arranged as concentric growth shells. AQP0{sup -/-}lenses were cataractous, lacked 'Y' sutures, ordered packing and well-defined lateral interdigitations. TgAQP1{sup +/+}/AQP0{sup -/-} lenses showed improvement in transparency and lateral interdigitations in the outer cortex while inner cortex and nuclear fibers were severely disintegrated. Transmission electron micrographs exhibited tightly packed fibercells in WT whereas AQP0{sup -/-} and TgAQP1{sup +/+}/AQP0{sup -/-}lenses had wide extracellular spaces. Fibers were easily separable by teasing in AQP0{sup -/-} and TgAQP1{sup +/+}/AQP0{sup -/-}lenses compared to WT. Our data suggest that the increased water permeability through AQP1 does not compensate for loss of AQP0 expression in TgAQP1{sup +/+}/AQP0{sup -/-} mice. Fibercell AQP0 expression is required to maintain their organization, which is a requisite for lenstransparency. AQP0 appears necessary for cell-to-cell adhesion and thereby to minimize light scattering since in the AQP0{sup -/-} and TgAQP1{sup +/+}/AQP0{sup -/-} lenses, fiber cell disorganization was evident.

Serological markers associated with neuromyelitis optica spectrum disorders in South India

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Lekha Pandit

2016-01-01

Full Text Available Background: Neuromyelitis optica spectrum disorders (NMOSDs represent 20% of all demyelinating disorders in South India. No studies have determined the seroprevalence to both antibodies against aquaporin-4FNx01 and antimyelin oligodendrocyte glycoprotein antibody (anti-MOG+ in this population. Objective: To identify and characterize seropositive patients for anti-aquaporin-4 antibody (anti-AQP4+ and anti-MOG+ in South India. Materials and Methods: We included 125 consecutive patients (15 children who were serologically characterized using live transfected cells to human M23-AQP4 or full-length MOG. Results: Among a total of 125 patients, 30.4% of patients were anti-AQP4+, 20% were anti-MOG+, and 49.6% were seronegative. No patient was positive for both. Anti-MOG+ patients represented 28.7% (25/87 of seronegative NMOSD. In comparison to anti-AQP4+ patients, anti-MOG+ patients were commonly male, had less frequent attacks and milder disability on expanded disability status score scale. Seronegative patients were also predominantly male, 36% (9/25 had monophasic longitudinally extensive transverse myelitis and disability was comparable with anti-AQP4+ patients. Lumbar cord involvement was common in anti-MOG+ and seronegatives, whereas anti-AQP4+ patients had more cervical lesions. Conclusion: Anti-AQP4+/anti-MOG + patients accounted for nearly half of the patients suspected of having NMOSD in South India, indicating that antibody testing may be useful on the management of subgroups with different prognosis.

Different relationships between temporal phylogenetic turnover and phylogenetic similarity and in two forests were detected by a new null model.

Science.gov (United States)

Huang, Jian-Xiong; Zhang, Jian; Shen, Yong; Lian, Ju-yu; Cao, Hong-lin; Ye, Wan-hui; Wu, Lin-fang; Bin, Yue

2014-01-01

Ecologists have been monitoring community dynamics with the purpose of understanding the rates and causes of community change. However, there is a lack of monitoring of community dynamics from the perspective of phylogeny. We attempted to understand temporal phylogenetic turnover in a 50 ha tropical forest (Barro Colorado Island, BCI) and a 20 ha subtropical forest (Dinghushan in southern China, DHS). To obtain temporal phylogenetic turnover under random conditions, two null models were used. The first shuffled names of species that are widely used in community phylogenetic analyses. The second simulated demographic processes with careful consideration on the variation in dispersal ability among species and the variations in mortality both among species and among size classes. With the two models, we tested the relationships between temporal phylogenetic turnover and phylogenetic similarity at different spatial scales in the two forests. Results were more consistent with previous findings using the second null model suggesting that the second null model is more appropriate for our purposes. With the second null model, a significantly positive relationship was detected between phylogenetic turnover and phylogenetic similarity in BCI at a 10 m×10 m scale, potentially indicating phylogenetic density dependence. This relationship in DHS was significantly negative at three of five spatial scales. This could indicate abiotic filtering processes for community assembly. Using variation partitioning, we found phylogenetic similarity contributed to variation in temporal phylogenetic turnover in the DHS plot but not in BCI plot. The mechanisms for community assembly in BCI and DHS vary from phylogenetic perspective. Only the second null model detected this difference indicating the importance of choosing a proper null model.

A Coding of Real Null Four-Momenta into World-Sheet Co-ordinates

OpenAIRE

Fairlie, David B.

2008-01-01

The results of minimizing the action for string-like systems on a simply-connected world sheet are shown to encode the Cartesian components of real null momentum four-vectors into co-ordinates on the world sheet. This identification arises consistently from different approaches to the problem.

On the Penrose inequality for dust null shells in the Minkowski spacetime of arbitrary dimension

International Nuclear Information System (INIS)

Mars, Marc; Soria, Alberto

2012-01-01

A particular, yet relevant, case of the Penrose inequality involves null shells propagating in the Minkowski spacetime. Despite previous claims in the literature, the validity of this inequality remains open. In this paper, we rewrite this inequality in terms of the geometry of the surface obtained by intersecting the past null cone of the original surface S with a constant time hyperplane and the 'time height' function of S over this hyperplane. We also specialize to the case when S lies in the past null cone of a point and show the validity of the corresponding inequality in any dimension (in four dimensions this inequality was proved by Tod (1985 Class. Quantum Grav. 2 L65-8). Exploiting properties of convex hypersurfaces in the Euclidean space, we write down the Penrose inequality in the Minkowski spacetime of an arbitrary dimension n + 2 as an inequality for two smooth functions on the sphere S n . We finally obtain a sufficient condition for the validity of the Penrose inequality in the four-dimensional Minkowski spacetime and show that this condition is satisfied by a large class of surfaces. (paper)

Bursty, Broadband Electromagnetic Waves Associated with Three-Dimensional Nulls Observed in Turbulent Magnetosheath Reconnection

Science.gov (United States)

Adrian, Mark L.; Wendel, D. E.

2012-01-01

We investigate observations of intense bursts of electromagnetic wave energy in association with the thin current layers of turbulent magnetosheath reconnection. These observed emissions - typically detected in the layers immediately outside of the current layer proper - form two distinct types: (i) broadband emissions that extend continuously to lOs of Hertz; and (ii) structured bursts of emitted energy that occur above 80-Hz, often displaying features reminiscent of absorption bands and are observed near the local minima in the magnetic field. We present detailed analyses of these intense bursts of electromagnetic energy and quantify their proximity to X-IO-nulls and magnetic spine connected null pairs, as well as their correlation - if any - to the amount of magnetic energy converted by the process of magnetic reconnection.

Possible Solution to Publication Bias Through Bayesian Statistics, Including Proper Null Hypothesis Testing

NARCIS (Netherlands)

Konijn, Elly A.; van de Schoot, Rens; Winter, Sonja D.; Ferguson, Christopher J.

2015-01-01

The present paper argues that an important cause of publication bias resides in traditional frequentist statistics forcing binary decisions. An alternative approach through Bayesian statistics provides various degrees of support for any hypothesis allowing balanced decisions and proper null

Three genes for mitochondrial proteins suppress null-mutations in both Afg3 and Rca1 when over-expressed.

Science.gov (United States)

Rep, M; Nooy, J; Guélin, E; Grivell, L A

1996-08-01

The AFG3 gene of Saccharomyces cerevisiae encodes a mitochondrial inner membrane protein with ATP-dependent protease activity. To gain more insight into the function of this protein, multi-copy suppressors of an afg3-null mutation were isolated. Three genes were found that restored partial growth on non-fermentable carbon sources, all of which affect the biogenesis of respiratory competent mitochondria: PIM1(LON) encodes a matrix-localized ATP-dependent protease involved in the turnover of matrix proteins; OXA1(PET1402) encodes a putative mitochondrial inner membrane protein involved in the biogenesis of the respiratory chain; and MBA1 encodes a mitochondrial protein required for optimal respiratory growth. All three genes also suppressed a null mutation in a related gene, RCA1, as well as in the combination of afg3- and rca1-null.

Extrasolar Planetary Imaging Coronagraph (EPIC): visible nulling cornagraph testbed results

Science.gov (United States)

Lyon, Richard G.; Clampin, Mark; Melnick, Gary; Tolls, Volker; Woodruff, Robert; Vasudevan, Gopal

2008-07-01

The Extrasolar Planetary Imaging Coronagraph (EPIC) is a NASA Astrophysics Strategic Mission Concept under study for the upcoming Exoplanet Probe. EPIC's mission would be to image and characterize extrasolar giant planets, and potential super-Earths, in orbits with semi-major axes between 2 and 10 AU. EPIC will provide insights into the physical nature of a variety of planets in other solar systems complimenting radial velocity (RV) and astrometric planet searches. It will detect and characterize the atmospheres of planets identified by radial velocity surveys and potentially some transits, determine orbital inclinations and masses, characterize the atmospheres of gas giants around A and F stars, observed the inner spatial structure and colors of inner Spitzer selected debris disks. EPIC would be launched into a heliocentric Earth trailing drift-away orbit, with a 3-year mission lifetime (5 year goal) and will revisit planets at least three times. The starlight suppression approach consists of a visible nulling coronagraph (VNC) that enables high order starlight suppression in broadband light. To demonstrate the VNC approach and advance it's technology readiness the NASA/Goddard Space Flight Center and Lockheed-Martin have developed a laboratory VNC and have demonstrated white light nulling. We will discuss our ongoing VNC work and show the latest results from the VNC testbed.

Plate with a hole obeys the averaged null energy condition

International Nuclear Information System (INIS)

Graham, Noah; Olum, Ken D.

2005-01-01

The negative energy density of Casimir systems appears to violate general relativity energy conditions. However, one cannot test the averaged null energy condition (ANEC) using standard calculations for perfectly reflecting plates, because the null geodesic would have to pass through the plates, where the calculation breaks down. To avoid this problem, we compute the contribution to ANEC for a geodesic that passes through a hole in a single plate. We consider both Dirichlet and Neumann boundary conditions in two and three space dimensions. We use a Babinet's principle argument to reduce the problem to a complementary finite disk correction to the perfect mirror result, which we then compute using scattering theory in elliptical and spheroidal coordinates. In the Dirichlet case, we find that the positive correction due to the hole overwhelms the negative contribution of the infinite plate. In the Neumann case, where the infinite plate gives a positive contribution, the hole contribution is smaller in magnitude, so again ANEC is obeyed. These results can be extended to the case of two plates in the limits of large and small hole radii. This system thus provides another example of a situation where ANEC turns out to be obeyed when one might expect it to be violated

Null strings and complex Einstein-Maxwell fields with cosmological constant

International Nuclear Information System (INIS)

Garcia, A.; Plebanski, J.F.; Robinson, I.

1977-01-01

Previous results of Plebanski and Robinson (Phys. Rev. Lett.; 37:493 (1976)) concerning left-degenerate Einstein-flat complex space-times and preliminary results concerning the electromagnetic field, are here generalized and worked out in some detail for the system of Einstein-Maxwell equations with a cosmological constant. On the assumption that there exists a congruence of totally null surfaces, the system is reduced to a pair of equations for the two unknown functions. (author)

In Search of the Null: The NCSA 2003 Presidential Address

Directory of Open Access Journals (Sweden)

Beth Davison

2003-10-01

Full Text Available Sociologists usually publish articles where the results show statistically significant differences between two groups of people. Results which show the opposite are generally called 'negative findings,' and are not considered publishable. Davison argues that we really ought to be looking for and encouraging the null finding, especially when social inequality and poverty are the issue. In addition, society as a whole should be working to eliminate poverty and inequality

Molecular bass for a malic enzyme null mutation

International Nuclear Information System (INIS)

Brown, M.L.; Wise, L.S.; Rubin, C.S.

1987-01-01

Many tissues from normal (wt) mice have cytosolic malic enzyme (ME) activity and express two mRNAs (2 and 3.1 kb) that code for a single ME polypeptide. Mod-1 null (M-n) mice lack cytosolic ME activity, but express 2.5 and 3.6 kb mRNAs that hybridize with wt ME cDNAs. To investigate the basis for the ME deficiency cDNAs corresponding to M-n ME RNA were cloned. A λgt11 library was prepared using M-n liver mRNA as a template. Wt ME cDNA probes hybridized with several recombinant phages and a 2kb insert with an atypical (non-wt) restriction pattern was subcloned in pGEM 1 and sequenced. The M-n ME cDNA contains an internal directly repeated sequence that corresponds to nts 1109-1617 in the coding region of wt ME cDNA. A restriction fragment from M-n ME cDNA that includes the first 204 bp of repeated sequence and 306 bp of contiguous 5' sequence was subcloned into pGEM 1 and used as a template for synthesizing 32 P-labeled anti-sense RNA. After hybridization with M-n liver RNA the 510 nt transcript was resistant to RNA digestion; after hybridization with wt RNA only fragments corresponding to the normally non-contiguous 204 bp and 306 bp segments of the insert were protected. Thus the partial duplication of coding sequence in M-n ME mRNA is confirmed. Analyses of intron-exon organization in the relevant regions of the wt and M-n ME genes will provide further insights into the mechanism underlying the ME null mutation

Is PMI the Hypothesis or the Null Hypothesis?

Science.gov (United States)

Tarone, Aaron M; Sanford, Michelle R

2017-09-01

Over the past several decades, there have been several strident exchanges regarding whether forensic entomologists estimate the postmortem interval (PMI), minimum PMI, or something else. During that time, there has been a proliferation of terminology reflecting this concern regarding "what we do." This has been a frustrating conversation for some in the community because much of this debate appears to be centered on what assumptions are acknowledged directly and which are embedded within a list of assumptions (or ignored altogether) in the literature and in case reports. An additional component of the conversation centers on a concern that moving away from the use of certain terminology like PMI acknowledges limitations and problems that would make the application of entomology appear less useful in court-a problem for lawyers, but one that should not be problematic for scientists in the forensic entomology community, as uncertainty is part of science that should and can be presented effectively in the courtroom (e.g., population genetic concepts in forensics). Unfortunately, a consequence of the way this conversation is conducted is that even as all involved in the debate acknowledge the concerns of their colleagues, parties continue to talk past one another advocating their preferred terminology. Progress will not be made until the community recognizes that all of the terms under consideration take the form of null hypothesis statements and that thinking about "what we do" as a null hypothesis has useful legal and scientific ramifications that transcend arguments over the usage of preferred terminology. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

3D Solar Null Point Reconnection MHD Simulations

Science.gov (United States)

Baumann, G.; Galsgaard, K.; Nordlund, Å.

2013-06-01

Numerical MHD simulations of 3D reconnection events in the solar corona have improved enormously over the last few years, not only in resolution, but also in their complexity, enabling more and more realistic modeling. Various ways to obtain the initial magnetic field, different forms of solar atmospheric models as well as diverse driving speeds and patterns have been employed. This study considers differences between simulations with stratified and non-stratified solar atmospheres, addresses the influence of the driving speed on the plasma flow and energetics, and provides quantitative formulas for mapping electric fields and dissipation levels obtained in numerical simulations to the corresponding solar quantities. The simulations start out from a potential magnetic field containing a null-point, obtained from a Solar and Heliospheric Observatory (SOHO) Michelson Doppler Imager (MDI) magnetogram magnetogram extrapolation approximately 8 hours before a C-class flare was observed. The magnetic field is stressed with a boundary motion pattern similar to - although simpler than - horizontal motions observed by SOHO during the period preceding the flare. The general behavior is nearly independent of the driving speed, and is also very similar in stratified and non-stratified models, provided only that the boundary motions are slow enough. The boundary motions cause a build-up of current sheets, mainly in the fan-plane of the magnetic null-point, but do not result in a flare-like energy release. The additional free energy required for the flare could have been partly present in non-potential form at the initial state, with subsequent additions from magnetic flux emergence or from components of the boundary motion that were not represented by the idealized driving pattern.

A Panel Test of Purchasing Power Parity Under the Null of Stationarity

OpenAIRE

Hunter, J; Simpson, M

2001-01-01

Purchasing Power Parity (PPP) is tested using a sample of real exchange rate data for twelve European countries. Acknowledging that Augmented Dickey Fuller tests have low power, we apply a Panel test that considers the null of stationarity and corrects for serial dependence using a non-parametric kernel based method.

Surprising structures hiding in Penrose’s future null infinity

Science.gov (United States)

Newman, Ezra T.

2017-07-01

Since the late1950s, almost all discussions of asymptotically flat (Einstein-Maxwell) space-times have taken place in the context of Penrose’s null infinity, I+. In addition, almost all calculations have used the Bondi coordinate and tetrad systems. Beginning with a known asymptotically flat solution to the Einstein-Maxwell equations, we show first, that there are other natural coordinate systems, near I+, (analogous to light-cones in flat-space) that are based on (asymptotically) shear-free null geodesic congruences (analogous to the flat-space case). Using these new coordinates and their associated tetrad, we define the complex dipole moment, (the mass dipole plus i times angular momentum), from the l  =  1 harmonic coefficient of a component of the asymptotic Weyl tensor. Second, from this definition, from the Bianchi identities and from the Bondi-Sachs mass and linear momentum, we show that there exists a large number of results—identifications and dynamics—identical to those of classical mechanics and electrodynamics. They include, among many others, {P}=M{v}+..., {L}= {r} × {P} , spin, Newton’s second law with the rocket force term (\\dotM v) and radiation reaction, angular momentum conservation and others. All these relations take place in the rather mysterious H-space rather than in space-time. This leads to the enigma: ‘why do these well known relations of classical mechanics take place in H-space?’ and ‘What is the physical meaning of H-space?’

Asymptotically shear-free and twist-free null geodesic congruences

International Nuclear Information System (INIS)

Kozameh, Carlos; Newman, Ezra T

2007-01-01

The Robinson-Trautman spacetime is a special case of asymptotically flat spacetimes that possess asymptotically shear-free and twist-free (surface forming) null geodesic congruences. In this paper we show that, although they are rare, a larger class of asymptotically flat spacetimes with this property does exist. In particular, we display the class of spacetimes that possess this dual property and demonstrate how these congruences can be found. In addition, we show that in each case the congruence is isolated in the sense that there are no other neighbouring congruences with this dual property

Five-dimensional null-cone structure of big bang singularity

Energy Technology Data Exchange (ETDEWEB)

Lauro, S.; Schucking, E.L.

1985-04-01

The Friedmann model PHI of positive space curvature, vanishing pressure and cosmological constant when isometrically imbedded as a hypersurface in five-dimensional Minkowski space MV is globally rigid: if F(PHI) and F'(PHI) are isometric embeddings in MV there is a motion of MV such that F'= F. The big bang singularity is the vertex of a null half-cone in MV. Global rigidity leads to an invariant characterization of the singularity. The structure of matter at the singularity is governed by the de Sitter group.

Five-dimensional null-cone structure of big bang singularity

International Nuclear Information System (INIS)

Lauro, S.; Schucking, E.L.

1985-01-01

The Friedmann model PHI of positive space curvature, vanishing pressure and cosmological constant when isometrically imbedded as a hypersurface in five-dimensional Minkowski space M 5 is globally rigid: if F(PHI) and F'(PHI) are isometric embeddings in M 5 there is a motion π of M 5 such that F'=π 0 F. The big bang singularity is the vertex of a null half-cone in M 5 . Global rigidity leads to an invariant characterization of the singularity. The structure of matter at the singularity is governed by the de Sitter group. (author)

Interpretation of Chinese Overt and Null Embedded Arguments by English-Speaking Learners

Science.gov (United States)

Zhao, Lucy Xia

2012-01-01

It has been proposed that external interfaces are vulnerable to residue optionality, whereas pure syntax and internal interfaces are acquirable in second language (L2) acquisition (Sorace, 2005, 2011; Sorace and Filiaci, 2006). The proposal was tested in this article through the interpretation of overt and null embedded arguments in L2 Chinese…

The Proatherogenic Effect of Chronic Nitric Oxide Synthesis Inhibition in ApoE-Null Mice Is Dependent on the Presence of PPARα

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Michal Vechoropoulos

2014-01-01

Full Text Available Inhibition of endothelial nitric oxide synthase (eNOS accelerates atherosclerosis in ApoE-null mice by impairing the balance between angiotensin II (AII and NO. Our previous data suggested a role for PPARα in the deleterious effect of the renin-angiotensin system (RAS. We tested the hypothesis that ApoE-null mice lacking PPARα (DKO mice would be resistant to the proatherogenic effect of NOS inhibition. DKO mice fed a Western diet were immune to the 23% worsening in aortic sinus plaque area seen in the ApoE-null animals under 12 weeks of NOS inhibition with a subpressor dose of L-NAME, P=0.002. This was accompanied by a doubling of reactive oxygen species (ROS- generating aortic NADPH oxidase activity (a target of AII, which paralleled Nox1 expression and by a 10-fold excess of the proatherogenic iNOS, P<0.01. L-NAME also caused a doubling of aortic renin and angiotensinogen mRNA level in the ApoE-null mice but not in the DKO, and it upregulated eNOS in the DKO mice only. These data suggest that, in the ApoE-null mouse, PPARα contributes to the proatherogenic effect of unopposed RAS/AII action induced by L-NAME, an effect which is associated with Nox1 and iNOS induction, and is independent of blood pressure and serum lipids.

Modular Hamiltonians for deformed half-spaces and the averaged null energy condition

Science.gov (United States)

Faulkner, Thomas; Leigh, Robert G.; Parrikar, Onkar; Wang, Huajia

2016-09-01

We study modular Hamiltonians corresponding to the vacuum state for deformed half-spaces in relativistic quantum field theories on {{R}}^{1,d-1} . We show that in addition to the usual boost generator, there is a contribution to the modular Hamiltonian at first order in the shape deformation, proportional to the integral of the null components of the stress tensor along the Rindler horizon. We use this fact along with monotonicity of relative entropy to prove the averaged null energy condition in Minkowski space-time. This subsequently gives a new proof of the Hofman-Maldacena bounds on the parameters appearing in CFT three-point functions. Our main technical advance involves adapting newly developed perturbative methods for calculating entanglement entropy to the problem at hand. These methods were recently used to prove certain results on the shape dependence of entanglement in CFTs and here we generalize these results to excited states and real time dynamics. We also discuss the AdS/CFT counterpart of this result, making connection with the recently proposed gravitational dual for modular Hamiltonians in holographic theories.

The gravitational exclusion principle and null states in anti-de Sitter space

International Nuclear Information System (INIS)

Castro, Alejandra; Maloney, Alexander; Hartman, Thomas

2011-01-01

The holographic principle implies a vast reduction in the number of degrees of freedom of quantum gravity. This idea can be made precise in AdS 3 , where the the stringy or gravitational exclusion principle asserts that certain perturbative excitations are not present in the exact quantum spectrum. We show that this effect is visible directly in the bulk gravity theory: the norm of the offending linearized state is zero or negative. When the norm is negative, the theory is signalling its own breakdown as an effective field theory; this provides a perturbative bulk explanation for the stringy exclusion principle. When the norm vanishes the bulk state is null rather than physical. This implies that certain non-trivial diffeomorphisms must be regarded as gauge symmetries rather than spectrum-generating elements of the asymptotic symmetry group. This leads to subtle effects in the computation of one-loop determinants for Einstein gravity, higher spin theories and topologically massive gravity in AdS 3 . In particular, heat kernel methods do not capture the correct spectrum of a theory with null states. Communicated by S Ross

MicroRNA Dysregulation in Liver and Pancreas of CMP-Neu5Ac Hydroxylase Null Mice Disrupts Insulin/PI3K-AKT Signaling

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Deug-Nam Kwon

2014-01-01

Full Text Available CMP-Neu5Ac hydroxylase (Cmah-null mice fed with a high-fat diet develop fasting hyperglycemia, glucose intolerance, and pancreatic β-cell dysfunction and ultimately develop characteristics of type 2 diabetes. The precise metabolic role of the Cmah gene remains poorly understood. This study was designed to investigate the molecular mechanisms through which microRNAs (miRNAs regulate type 2 diabetes. Expression profiles of miRNAs in Cmah-null mouse livers were compared to those of control mouse livers. Liver miFinder miRNA PCR arrays (n=6 showed that eight miRNA genes were differentially expressed between the two groups. Compared with controls, seven miRNAs were upregulated and one miRNA was downregulated in Cmah-null mice. Specifically, miR-155-5p, miR-425-5p, miR-15a-5p, miR-503-5p, miR-16-5p, miR-29a-3p, and miR-29b-3p were significantly upregulated in the liver and pancreas of Cmah-null mice. These target miRNAs are closely associated with dysregulation of insulin/PI3K-AKT signaling, suggesting that the Cmah-null mice could be a useful model for studying diabetes.

Aquaporin-4 autoantibodies in neuromyelitis optica spectrum disorders: comparison between tissue-based and cell-based indirect immunofluorescence assays

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Chan Koon H

2010-09-01

Full Text Available Abstract Background Neuromyelitis optica spectrum disorders (NMOSD are severe central nervous system inflammatory demyelinating disorders (CNS IDD characterized by monophasic or relapsing, longitudinally extensive transverse myelitis (LETM and/or optic neuritis (ON. A significant proportion of NMOSD patients are seropositive for aquaporin-4 (AQP4 autoantibodies. We compared the AQP4 autoantibody detection rates of tissue-based indirect immunofluorescence assay (IIFA and cell-based IIFA. Methods Serum of Chinese CNS IDD patients were assayed for AQP4 autoantibodies by tissue-based IIFA using monkey cerebellum and cell-based IIFA using transfected HEK293 cells which express human AQP4 on their cell membranes. Results In total, 128 CNS IDD patients were studied. We found that 78% of NMO patients were seropositive for AQP4 autoantibodies by cell-based IIFA versus 61% by tissue-based IFA (p = 0.250, 75% of patients having relapsing myelitis (RM with LETM were seropositive by cell-based IIFA versus 50% by tissue-based IIFA (p = 0.250, and 33% of relapsing ON patients were seropositive by cell-based IIFA versus 22% by tissue-based IIFA (p = 1.000; however the differences were not statistically significant. All patients seropositive by tissue-based IIFA were also seropositive for AQP4 autoantibodies by cell-based IIFA. Among 29 NMOSD patients seropositive for AQP4 autoantibodies by cell-based IIFA, 20 (69% were seropositive by tissue-based IIFA. The 9 patients seropositive by cell-based IIFA while seronegative by tissue-based IIFA had NMO (3, RM with LETM (3, a single attack of LETM (1, relapsing ON (1 and a single ON attack (1. Among 23 NMO or RM patients seropositive for AQP4 autoantibodies by cell-based IIFA, comparison between those seropositive (n = 17 and seronegative (n = 6 by tissue-based IIFA revealed no differences in clinical and neuroradiological characteristics between the two groups. Conclusion Cell-based IIFA is slightly more sensitive

Cadmium modulates adipocyte functions in metallothionein-null mice

Energy Technology Data Exchange (ETDEWEB)

Kawakami, Takashige; Nishiyama, Kaori; Kadota, Yoshito; Sato, Masao; Inoue, Masahisa; Suzuki, Shinya, E-mail: suzukis@ph.bunri-u.ac.jp

2013-11-01

Our previous study has demonstrated that exposure to cadmium (Cd), a toxic heavy metal, causes a reduction of adipocyte size and the modulation of adipokine expression. To further investigate the significance of the Cd action, we studied the effect of Cd on the white adipose tissue (WAT) of metallothionein null (MT{sup −/−}) mice, which cannot form atoxic Cd–MT complexes and are used for evaluating Cd as free ions, and wild type (MT{sup +/+}) mice. Cd administration more significantly reduced the adipocyte size of MT{sup −/−} mice than that of MT{sup +/+} mice. Cd exposure also induced macrophage recruitment to WAT with an increase in the expression level of Ccl2 (MCP-1) in the MT{sup −/−} mice. The in vitro exposure of Cd to adipocytes induce triglyceride release into culture medium, decrease in the expression levels of genes involved in fatty acid synthesis and lipid hydrolysis at 24 h, and at 48 h increase in phosphorylation of the lipid-droplet-associated protein perilipin, which facilitates the degradation of stored lipids in adipocytes. Therefore, the reduction in adipocyte size by Cd may arise from an imbalance between lipid synthesis and lipolysis. In addition, the expression levels of leptin, adiponectin and resistin decreased in adipocytes. Taken together, exposure to Cd may induce unusually small adipocytes and modulate the expression of adipokines differently from the case of physiologically small adipocytes, and may accelerate the risk of developing insulin resistance and type 2 diabetes. - Highlights: • Cd causes a marked reduction in adipocyte size in MT-null mice. • Cd enhances macrophage migration into adipose tissue and disrupt adipokine secretion. • MT gene alleviates Cd-induced adipocyte dysfunctions. • Cd enhances the degradation of stored lipids in adipocytes, mediated by perilipin. • Cd induces unusually small adipocytes and the abnormal expression of adipokines.

An Innovative Approach to Balancing Chemical-Reaction Equations: A Simplified Matrix-Inversion Technique for Determining The Matrix Null Space

OpenAIRE

Thorne, Lawrence R.

2011-01-01

I propose a novel approach to balancing equations that is applicable to all chemical-reaction equations; it is readily accessible to students via scientific calculators and basic computer spreadsheets that have a matrix-inversion application. The new approach utilizes the familiar matrix-inversion operation in an unfamiliar and innovative way; its purpose is not to identify undetermined coefficients as usual, but, instead, to compute a matrix null space (or matrix kernel). The null space then...

Reduced infarct size in neuroglobin-null mice after experimental stroke in vivo

DEFF Research Database (Denmark)

Raida, Zindy; Hundahl, Christian Ansgar; Kelsen, Jesper

2012-01-01

Neuroglobin is considered to be a novel important pharmacological target in combating stroke and neurodegenerative disorders, although the mechanism by which this protection is accomplished remains an enigma. We hypothesized that if neuroglobin is directly involved in neuroprotection, then perman......, then permanent cerebral ischemia would lead to larger infarct volumes in neuroglobin-null mice than in wild-type mice....

Heat Shock Proteins 60 and 70 Specific Proinflammatory and Cytotoxic Response of CD4+CD28null Cells in Chronic Kidney Disease

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Ashok K. Yadav

2013-01-01

Full Text Available Background. CD4+CD28null T cells are expanded in peripheral blood of patients with chronic kidney disease and associated with subclinical atherosclerosis. However, triggers for the oligoclonal expansion and activation of these cells are not clear. Methods. We investigated twenty-five stage V-IV chronic kidney disease (CKD patients and eight healthy subjects (HC. Peripheral mononuclear cells were isolated and incubated with heat shock protein- (HSP 60 and 70. CD4+CD28null and CD4+CD28+ cells were sorted by flowcytometry and antigen specific response was assessed by the mRNA and protein expression of interferon (IFN-γ, perforin, and granzyme B using qRT-PCR and Elispot. Results. The basal mRNA expression of IFN-γ, perforin, and granzyme B in CD4+CD28null cells was higher in subjects with CKD compared to that in HC (P<0.0001. Subjects with CKD also showed expression of IFN-γ, perforin, and granzyme B in the CD4+CD28+ subset, but this was much weaker than that seen in the CD4+CD28null population (P<0.0001. We did not note the expression of these molecules at mRNA or protein level in either subset of CD4 cells in HC. After incubation with HSP60 and HSP70, CD4+CD28null cells showed increased expression at mRNA (P<0.001 and protein level (P<0.001. CD4+CD28+ cells also showed a weak increase in expression. No antigen-specific response was noted in HC. Conclusion. These data show that CD4+CD28null cells in subjects with CKD react with HSP60 and HSP70 by upregulating the expression of IFN-γ, perforin and granzyme B. Increased circulating level of HSP60 and HSP70 might play a role in initiation and/or progression of atherosclerosis in CKD subjects through perturbation of CD4+CD28null cells.

Does horizon entropy satisfy a quantum null energy conjecture?

Science.gov (United States)

Fu, Zicao; Marolf, Donald

2016-12-01

A modern version of the idea that the area of event horizons gives 4G times an entropy is the Hubeny-Rangamani causal holographic information (CHI) proposal for holographic field theories. Given a region R of a holographic QFTs, CHI computes A/4G on a certain cut of an event horizon in the gravitational dual. The result is naturally interpreted as a coarse-grained entropy for the QFT. CHI is known to be finitely greater than the fine-grained Hubeny-Rangamani-Takayanagi (HRT) entropy when \\partial R lies on a Killing horizon of the QFT spacetime, and in this context satisfies other non-trivial properties expected of an entropy. Here we present evidence that it also satisfies the quantum null energy condition (QNEC), which bounds the second derivative of the entropy of a quantum field theory on one side of a non-expanding null surface by the flux of stress-energy across the surface. In particular, we show CHI to satisfy the QNEC in 1  +  1 holographic CFTs when evaluated in states dual to conical defects in AdS3. This surprising result further supports the idea that CHI defines a useful notion of coarse-grained holographic entropy, and suggests unprecedented bounds on the rate at which bulk horizon generators emerge from a caustic. To supplement our motivation, we include an appendix deriving a corresponding coarse-grained generalized second law for 1  +  1 holographic CFTs perturbatively coupled to dilaton gravity.

The role of renal aquaporin 2 in the alleviation of dehydration associated with diabetic polyuria in KKAy mice.

Science.gov (United States)

Satake, Masako; Ikarashi, Nobutomo; Ichikawa, Yuhei; Maniwa, Ayaka; Toda, Takahiro; Ito, Kiyomi; Ochiai, Wataru; Sugiyama, Kiyoshi

2010-10-09

Polyuria is a symptom that appears in association with diabetes mellitus. Because sustained polyuria causes serious dehydration, it is believed that the body has a compensating mechanism to alleviate dehydration. In the present study, the role of renal aquaporin 2 (AQP2) in the compensating mechanism was investigated in KKAy mice, a type 2 diabetes model. The renal AQP2 expression levels in KKAy mice aged between 5 and 24 weeks were determined using Western blotting. The hypothalamic vasopressin mRNA expression levels also were measured by real-time RT-PCR. Insulin was subcutaneously administered to 11-week-old KKAy mice twice a day for 7 days. After insulin treatment, the renal AQP2 protein expression and the hypothalamic vasopressin mRNA expression were measured. The urinary volumes of 5- and 12-week-old KKAy mice were 1.5 ± 0.3 mL and 9.5 ± 1.2 mL, respectively. The inner medullary AQP2 protein expression of 12-week-old KKAy mice was approximately 2.5-fold higher than that of 5-week-old KKAy mice. The hypothalamic vasopressin mRNA expression of 12-week-old KKAy mice was approximately twice that of 5-week-old KKAy mice. Insulin treatment in KKAy mice resulted in a significant reduction in the plasma glucose level, urinary volume, and inner medullary AQP2 protein and hypothalamic vasopressin mRNA expression. The present study demonstrated that AQP2 is a renal functional molecule of vasopressin that controls urinary volume and that AQP2 in the kidney increases to alleviate dehydration due to type 2 diabetes with polyuria. Copyright © 2010 Elsevier Inc. All rights reserved.

Theory of synergistic effects: Hill-type response surfaces as 'null-interaction' models for mixtures.

Science.gov (United States)

Schindler, Michael

2017-08-02

The classification of effects caused by mixtures of agents as synergistic, antagonistic or additive depends critically on the reference model of 'null interaction'. Two main approaches are currently in use, the Additive Dose (ADM) or concentration addition (CA) and the Multiplicative Survival (MSM) or independent action (IA) models. We compare several response surface models to a newly developed Hill response surface, obtained by solving a logistic partial differential equation (PDE). Assuming that a mixture of chemicals with individual Hill-type dose-response curves can be described by an n-dimensional logistic function, Hill's differential equation for pure agents is replaced by a PDE for mixtures whose solution provides Hill surfaces as 'null-interaction' models and relies neither on Bliss independence or Loewe additivity nor uses Chou's unified general theory. An n-dimensional logistic PDE decribing the Hill-type response of n-component mixtures is solved. Appropriate boundary conditions ensure the correct asymptotic behaviour. Mathematica 11 (Wolfram, Mathematica Version 11.0, 2016) is used for the mathematics and graphics presented in this article. The Hill response surface ansatz can be applied to mixtures of compounds with arbitrary Hill parameters. Restrictions which are required when deriving analytical expressions for response surfaces from other principles, are unnecessary. Many approaches based on Loewe additivity turn out be special cases of the Hill approach whose increased flexibility permits a better description of 'null-effect' responses. Missing sham-compliance of Bliss IA, known as Colby's model in agrochemistry, leads to incompatibility with the Hill surface ansatz. Examples of binary and ternary mixtures illustrate the differences between the approaches. For Hill-slopes close to one and doses below the half-maximum effect doses MSM (Colby, Bliss, Finney, Abbott) predicts synergistic effects where the Hill model indicates 'null

Renal aquaporins and water balance disorders

DEFF Research Database (Denmark)

Kortenoeven, Marleen; Fenton, Robert A.

2013-01-01

BACKGROUND: Aquaporins (AQPs) are a family of proteins that can act as water channels. Regulation of AQPs is critical to osmoregulation and the maintenance of body water homeostasis. Eight AQPs are expressed in the kidney of which five have been shown to play a role in body water balance; AQP1, A......-solute diet and diuretics. GENERAL SIGNIFICANCE: In recent years, our understanding of the underlying mechanisms of water balance disorders has increased enormously, which has opened up several possible new treatment strategies.......BACKGROUND: Aquaporins (AQPs) are a family of proteins that can act as water channels. Regulation of AQPs is critical to osmoregulation and the maintenance of body water homeostasis. Eight AQPs are expressed in the kidney of which five have been shown to play a role in body water balance; AQP1, AQP......2, AQP3, AQP4 and AQP7. AQP2 in particular is regulated by vasopressin. SCOPE OF REVIEW: This review summarizes our current knowledge of the underlying mechanisms of various water balance disorders and their treatment strategies. MAJOR CONCLUSIONS: Dysfunctions of AQPs are involved in disorders...

Experimental measurement of magnetic field null in the vacuum chamber of KTM tokamak based on matrix of 2D Hall sensors

Energy Technology Data Exchange (ETDEWEB)

Shapovalov, G.; Chektybayev, B., E-mail: chektybaev@nnc.kz; Sadykov, A.; Skakov, M.; Kupishev, E.

2016-11-15

Experimental technique of measurement of magnetic field null region inside of the KTM tokamak vacuum chamber has been developed. Square matrix of 36 2D Hall sensors, which used in the technique, allows carrying out direct measurements of poloidal magnetic field dynamics in the vacuum chamber. To better measuring accuracy, Hall sensor’s matrix was calibrated with commercial Helmholtz coils and in situ measurement of defined magnetic field from poloidal and toroidal coils. Standard KTM Data-Acquisition System has been used to collect data from Hall sensors. Experimental results of measurement of magnetic field null in the vacuum chamber of KTM are shown in the paper. Additionally results of the magnetic field null reconstruction from signals of inductive total flux loops are shown in the paper.

Toll-like receptor 4 mutant and null mice retain morphine-induced tolerance, hyperalgesia, and physical dependence.

Directory of Open Access Journals (Sweden)

Theresa Alexandra Mattioli

Full Text Available The innate immune system modulates opioid-induced effects within the central nervous system and one target that has received considerable attention is the toll-like receptor 4 (TLR4. Here, we examined the contribution of TLR4 in the development of morphine tolerance, hyperalgesia, and physical dependence in two inbred mouse strains: C3H/HeJ mice which have a dominant negative point mutation in the Tlr4 gene rendering the receptor non-functional, and B10ScNJ mice which are TLR4 null mutants. We found that neither acute antinociceptive response to a single dose of morphine, nor the development of analgesic tolerance to repeated morphine treatment, was affected by TLR4 genotype. Likewise, opioid induced hyperalgesia and opioid physical dependence (assessed by naloxone precipitated withdrawal were not altered in TLR4 mutant or null mice. We also examined the behavioural consequence of two stereoisomers of naloxone: (- naloxone, an opioid receptor antagonist, and (+ naloxone, a purported antagonist of TLR4. Both stereoisomers of naloxone suppressed opioid induced hyperalgesia in wild-type control, TLR4 mutant, and TLR4 null mice. Collectively, our data suggest that TLR4 is not required for opioid-induced analgesic tolerance, hyperalgesia, or physical dependence.

Internalizing Null Extraterrestrial "Signals": An Astrobiological App for a Technological Society

OpenAIRE

Chaisson, Eric J.

2014-01-01

One of the beneficial outcomes of searching for life in the Universe is that it grants greater awareness of our own problems here on Earth. Lack of contact with alien beings to date might actually comprise a null "signal" pointing humankind toward a viable future. Astrobiology has surprising practical applications to human society; within the larger cosmological context of cosmic evolution, astrobiology clarifies the energetic essence of complex systems throughout the Universe, including tech...

Characterizing the role of endothelin-1 in the progression of cardiac hypertrophy in aryl hydrocarbon receptor (AhR) null mice

International Nuclear Information System (INIS)

Lund, Amie K.; Goens, M. Beth; Nunez, Bethany A.; Walker, Mary K.

2006-01-01

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor characterized to play a role in detection and adaptation to environmental stimuli. Genetic deletion of AhR results in hypertension, and cardiac hypertrophy and fibrosis, associated with elevated plasma angiotensin II (Ang II) and endothelin-1 (ET-1), thus AhR appears to contribute to cardiovascular homeostasis. In these studies, we tested the hypothesis that ET-1 mediates cardiovascular pathology in AhR null mice via ET A receptor activation. First, we determine the time courses of cardiac hypertrophy, and of plasma and tissue ET-1 expression in AhR wildtype and null mice. AhR null mice exhibited increases in heart-to-body weight ratio and age-related expression of cardiac hypertrophy markers, β-myosin heavy chain (β-MHC), and atrial natriuretic factor (ANF), which were significant at 2 months. Similarly, plasma and tissue ET-1 expression was significantly elevated at 2 months and increased further with age. Second, AhR null mice were treated with ET A receptor antagonist, BQ-123 (100 nmol/kg/day), for 7, 28, or 58 days and blood pressure, cardiac fibrosis, and cardiac hypertrophy assessed, respectively. BQ-123 for 7 days significantly reduced mean arterial pressure in conscious, catheterized mice. BQ-123 for 28 days significantly reduced the histological appearance of cardiac fibrosis. Treatment for 58 days significantly reduced cardiac mass, assessed by heart weight, echocardiography, and β-MHC and ANF expression; and reduced cardiac fibrosis as determined by osteopontin and collagen I mRNA expression. These findings establish ET-1 and the ET A receptor as primary determinants of hypertension and cardiac pathology in AhR null mice

Mice null for the deubiquitinase USP18 spontaneously develop leiomyosarcomas

International Nuclear Information System (INIS)

Chinyengetere, Fadzai; Sekula, David J.; Lu, Yun; Giustini, Andrew J.; Sanglikar, Aarti; Kawakami, Masanori; Ma, Tian; Burkett, Sandra S.; Eisenberg, Burton L.; Wells, Wendy A.; Hoopes, Paul J.; Demicco, Elizabeth G.; Lazar, Alexander J; Torres, Keila E.; Memoli, Vincent; Freemantle, Sarah J.; Dmitrovsky, Ethan

2015-01-01

USP18 (ubiquitin-specific protease 18) removes ubiquitin-like modifier interferon stimulated gene 15 (ISG15) from conjugated proteins. USP18 null mice in a FVB/N background develop tumors as early as 2 months of age. These tumors are leiomyosarcomas and thus represent a new murine model for this disease. Heterozygous USP18 +/− FVB/N mice were bred to generate wild-type, heterozygous and homozygous cohorts. Tumors were characterized immunohistochemically and two cell lines were derived from independent tumors. Cell lines were karyotyped and their responses to restoration of USP18 activity assessed. Drug testing and tumorigenic assays were also performed. USP18 immunohistochemical staining in a large series of human leiomyosacomas was examined. USP18 −/− FVB/N mice spontaneously develop tumors predominantly on the back of the neck with most tumors evident between 6–12 months (80 % penetrance). Immunohistochemical characterization of the tumors confirmed they were leiomyosarcomas, which originate from smooth muscle. Restoration of USP18 activity in sarcoma-derived cell lines did not reduce anchorage dependent or independent growth or xenograft tumor formation demonstrating that these cells no longer require USP18 suppression for tumorigenesis. Karyotyping revealed that both tumor-derived cell lines were aneuploid with extra copies of chromosomes 3 and 15. Chromosome 15 contains the Myc locus and MYC is also amplified in human leiomyosarcomas. MYC protein levels were elevated in both murine leiomyosarcoma cell lines. Stabilized P53 protein was detected in a subset of these murine tumors, another feature of human leiomyosarcomas. Immunohistochemical analyses of USP18 in human leiomyosarcomas revealed a range of staining intensities with the highest USP18 expression in normal vascular smooth muscle. USP18 tissue array analysis of primary leiomyosarcomas from 89 patients with a clinical database revealed cases with reduced USP18 levels had a significantly

A robust null hypothesis for the potential causes of megadrought in western North America

Science.gov (United States)

Ault, T.; St George, S.; Smerdon, J. E.; Coats, S.; Mankin, J. S.; Cruz, C. C.; Cook, B.; Stevenson, S.

2017-12-01

The western United States was affected by several megadroughts during the last 1200 years, most prominently during the Medieval Climate Anomaly (MCA: 800 to 1300 CE). A null hypothesis is developed to test the possibility that, given a sufficiently long period of time, these events are inevitable and occur purely as a consequence of internal climate variability. The null distribution of this hypothesis is populated by a linear inverse model (LIM) constructed from global sea-surface temperature anomalies and self-calibrated Palmer Drought Severity Index data for North America. Despite being trained only on seasonal data from the late 20th century, the LIM produces megadroughts that are comparable in their duration, spatial scale, and magnitude as the most severe events of the last 12 centuries. The null hypothesis therefore cannot be rejected with much confidence when considering these features of megadrought, meaning that similar events are possible today, even without any changes to boundary conditions. In contrast, the observed clustering of megadroughts in the MCA, as well as the change in mean hydroclimate between the MCA and the 1500-2000 period, are more likely to have been caused by either external forcing or by internal climate variability not well sampled during the latter half of the Twentieth Century. Finally, the results demonstrate the LIM is a viable tool for determining whether paleoclimate reconstructions events should be ascribed to external forcings, "out of sample" climate mechanisms, or if they are consistent with the variability observed during the recent period.

The new null testing method for the special optical window

Science.gov (United States)

Huang, Changchun

2009-07-01

The high speed, high precision and wide range specifications are requirement for the modern aircraft, which the traditional hemispherical dome can't achieve now, and the novel conformal window instead can enhance the aerodynamic performance of the aircraft obviously. To reduce the aerodynamic drag and radar cross-section, the window geometry is generally aspheric in shape. As a result, the involved fabrication and testing processes are much more challenging than that of conventional optics and must be mastered before these windows and systems can be implemented at an acceptable cost and risk. Metrology is one of the critical areas required to advance the conformal window technology. But as the surface of these conformal windows is not the traditional sphere lens, the measurement method for it is infeasible with the conventional optics measurement processes. This paper we express the development of testing technology for the special conformal windows in brief, and emphatically introduces one available novel testing method- a new null testing, and here based on the theory of compensation methods, The principle of Offner's refractive null lens has been extended to test the transmission wavefront through conformal window optics and provide feedback during surface fabrication. a compensator system for the was designed for the conformal window is given which parameters are 100mm for its aperture and two parabolic surface as conformal window, the final residual wavefront error(RMS) of which is less than 1/20λ(λ=632.8nm).

Novel Remarks on Point Mass Sources, Firewalls, Null Singularities and Gravitational Entropy

Science.gov (United States)

Perelman, Carlos Castro

2016-01-01

A continuous family of static spherically symmetric solutions of Einstein's vacuum field equations with a spatial singularity at the origin r = 0 is found. These solutions are parametrized by a real valued parameter λ (ranging from 0 to 1) and such that the radial horizon's location is displaced continuously towards the singularity ( r = 0 ) as λ increases. In the extreme limit λ = 1, the location of the singularity and horizon merges leading to a null singularity. In this extreme case, any infalling observer hits the null singularity at the very moment he/she crosses the horizon. This fact may have important consequences for the resolution of the fire wall problem and the complementarity controversy in black holes. An heuristic argument is provided how one might avoid the Hawking particle emission process in this extreme case when the singularity and horizon merges. The field equations due to a delta-function point-mass source at r = 0 are solved and the Euclidean gravitational action corresponding to those solutions is evaluated explicitly. It is found that the Euclidean action is precisely equal to the black hole entropy (in Planck area units). This result holds in any dimensions D ≥ 3.

In-situ observations of flux ropes formed in association with a pair of spiral nulls in magnetotail plasmas

Energy Technology Data Exchange (ETDEWEB)

Guo, Ruilong; Xie, Lun; He, Jiansen [School of Earth and Space Sciences, Peking University, Beijing 100871 (China); Pu, Zuyin; Fu, Suiyan [School of Earth and Space Sciences, Peking University, Beijing 100871 (China); PKU/UCLA Joint Research Institute in Science and Engineering, Peking University, Beijing (China); Chen, Li-Jen [NASA Goddard Space Flight Center, Greenbelt, Maryland 20771 (United States); Wang, Xiaogang [Harbin Institute of Technology, Harbin 150001 (China); Dunlop, Malcolm [School of Astronautics, Beihang University, Beijing 100191 (China); RAL Space, Rutherford Appleton Laboratory, STFC, Didcot OX11 0QX (United Kingdom); Bogdanova, Yulia V. [RAL Space, Rutherford Appleton Laboratory, STFC, Didcot OX11 0QX (United Kingdom); Yao, Zhonghua; Fazakerley, Andrew N. [UCL Mullard Space Science Laboratory, Dorking RH5 6NT (United Kingdom); Xiao, Chijie [School of Physics, Peking University, Beijing 100871 (China)

2016-05-15

Signatures of secondary islands are frequently observed in the magnetic reconnection regions of magnetotail plasmas. In this paper, magnetic structures with the secondary-island signatures observed by Cluster are reassembled by a fitting-reconstruction method. The results show three-dimensionally that a secondary island event can manifest the flux rope formed with an A{sub s}-type null and a B{sub s}-type null paired via their spines. We call this A{sub s}-spine-B{sub s}-like configuration the helically wrapped spine model. The reconstructed field lines wrap around the spine to form the flux rope, and an O-type topology is therefore seen on the plane perpendicular to the spine. Magnetized electrons are found to rotate on and cross the fan surface, suggesting that both the torsional-spine and the spine-fan reconnection take place in the configuration. Furthermore, detailed analysis implies that the spiral nulls and flux ropes were locally generated nearby the spacecraft in the reconnection outflow region, indicating that secondary reconnection may occur in the exhaust away from the primary reconnection site.

In-situ observations of flux ropes formed in association with a pair of spiral nulls in magnetotail plasmas

International Nuclear Information System (INIS)

Guo, Ruilong; Xie, Lun; He, Jiansen; Pu, Zuyin; Fu, Suiyan; Chen, Li-Jen; Wang, Xiaogang; Dunlop, Malcolm; Bogdanova, Yulia V.; Yao, Zhonghua; Fazakerley, Andrew N.; Xiao, Chijie

2016-01-01

Signatures of secondary islands are frequently observed in the magnetic reconnection regions of magnetotail plasmas. In this paper, magnetic structures with the secondary-island signatures observed by Cluster are reassembled by a fitting-reconstruction method. The results show three-dimensionally that a secondary island event can manifest the flux rope formed with an A_s-type null and a B_s-type null paired via their spines. We call this A_s-spine-B_s-like configuration the helically wrapped spine model. The reconstructed field lines wrap around the spine to form the flux rope, and an O-type topology is therefore seen on the plane perpendicular to the spine. Magnetized electrons are found to rotate on and cross the fan surface, suggesting that both the torsional-spine and the spine-fan reconnection take place in the configuration. Furthermore, detailed analysis implies that the spiral nulls and flux ropes were locally generated nearby the spacecraft in the reconnection outflow region, indicating that secondary reconnection may occur in the exhaust away from the primary reconnection site.

Differential expression of aquaporin-3 and aquaporin-5 in pancreatic ductal adenocarcinoma.

Science.gov (United States)

Direito, Inês; Paulino, Jorge; Vigia, Emanuel; Brito, Maria Alexandra; Soveral, Graça

2017-06-01

Aquaporin-5 (AQP5) and -3 (AQP3) are protein channels that showed to be up-regulated in a variety of tumors. Our goal was to investigate the expression pattern of AQP5 and AQP3 in pancreatic ductal adenocarcinomas (PDA) and correlate with cell proliferation, tumor stage and progression, and clinical significance. 35 PDA samples in different stages of differentiation and locations were analyzed by immunohistochemistry for expression of AQP5, AQP3 and several markers of cell proliferation and tumorigenesis. In PDA samples AQP5 was overexpressed in the apical membrane of intercalated and intralobular ductal cells while AQP3 was expressed at the plasma membrane of ductal cells. AQP5 was also found in infiltrative cancer cells in duodenum. Simultaneous overexpression of EGFR, Ki-67, and CK7, with decreased E-cad and increased Vim that characterize epithelial mesenchymal transition, tumor formation and invasion, strongly suggest AQP3 and AQP5 involvement in cell proliferation and transformation. AQP3 overexpression is reinforced in late and more aggressive PDA stages whereas AQP5 is related with tumor differentiation, suggesting it may represent a novel marker for PDA aggressiveness and intestinal infiltration. These findings suggest AQP3 and AQP5 involvement in PDA development and the usefulness of AQP5 in early PDA diagnosis. © 2017 Wiley Periodicals, Inc.

Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact

DEFF Research Database (Denmark)

Mulder, Hindrik; Sörhede-Winzell, Maria; Contreras, Juan Antonio

2003-01-01

of increased amounts of insulin. Impaired insulin sensitivity was further indicated by retarded glucose disposal during an insulin tolerance test. A euglycemic hyperinsulinemic clamp revealed that hepatic glucose production was insufficiently blocked by insulin in HSL null mice. In vitro, insulin......-stimulated glucose uptake into soleus muscle, and lipogenesis in adipocytes were moderately reduced, suggesting additional sites of insulin resistance. Morphometric analysis of pancreatic islets revealed a doubling of beta-cell mass in HSL null mice, which is consistent with an adaptation to insulin resistance....... Insulin secretion in vitro, examined by perifusion of isolated islets, was not impacted by HSL deficiency. Thus, HSL deficiency results in a moderate impairment of insulin sensitivity in multiple target tissues of the hormone but is compensated by hyperinsulinemia....

Enhanced endotoxin sensitivity in fps/fes-null mice with minimal defects in hematopoietic homeostasis.

Science.gov (United States)

Zirngibl, Ralph A; Senis, Yotis; Greer, Peter A

2002-04-01

The fps/fes proto-oncogene encodes a cytoplasmic protein tyrosine kinase implicated in growth factor and cytokine receptor signaling and thought to be essential for the survival and terminal differentiation of myeloid progenitors. Fps/Fes-null mice were healthy and fertile, displayed slightly reduced numbers of bone marrow myeloid progenitors and circulating mature myeloid cells, and were more sensitive to lipopolysaccharide (LPS). These phenotypes were rescued using a fps/fes transgene. This confirmed that Fps/Fes is involved in, but not required for, myelopoiesis and that it plays a role in regulating the innate immune response. Bone marrow-derived Fps/Fes-null macrophages showed no defects in granulocyte-macrophage colony-stimulating factor-, interleukin 6 (IL-6)-, or IL-3-induced activation of signal transducer and activator of transcription 3 (Stat3) and Stat5A or LPS-induced degradation of I kappa B or activation of p38, Jnk, Erk, or Akt.

Null stream analysis of Pulsar Timing Array data: localisation of resolvable gravitational wave sources

Science.gov (United States)

Goldstein, Janna; Veitch, John; Sesana, Alberto; Vecchio, Alberto

2018-04-01

Super-massive black hole binaries are expected to produce a gravitational wave (GW) signal in the nano-Hertz frequency band which may be detected by pulsar timing arrays (PTAs) in the coming years. The signal is composed of both stochastic and individually resolvable components. Here we develop a generic Bayesian method for the analysis of resolvable sources based on the construction of `null-streams' which cancel the part of the signal held in common for each pulsar (the Earth-term). For an array of N pulsars there are N - 2 independent null-streams that cancel the GW signal from a particular sky location. This method is applied to the localisation of quasi-circular binaries undergoing adiabatic inspiral. We carry out a systematic investigation of the scaling of the localisation accuracy with signal strength and number of pulsars in the PTA. Additionally, we find that source sky localisation with the International PTA data release one is vastly superior than what is achieved by its constituent regional PTAs.

Genome-Wide Identification and Expression Analyses of Aquaporin Gene Family during Development and Abiotic Stress in Banana

Science.gov (United States)

Hu, Wei; Hou, Xiaowan; Huang, Chao; Yan, Yan; Tie, Weiwei; Ding, Zehong; Wei, Yunxie; Liu, Juhua; Miao, Hongxia; Lu, Zhiwei; Li, Meiying; Xu, Biyu; Jin, Zhiqiang

2015-01-01

Aquaporins (AQPs) function to selectively control the flow of water and other small molecules through biological membranes, playing crucial roles in various biological processes. However, little information is available on the AQP gene family in bananas. In this study, we identified 47 banana AQP genes based on the banana genome sequence. Evolutionary analysis of AQPs from banana, Arabidopsis, poplar, and rice indicated that banana AQPs (MaAQPs) were clustered into four subfamilies. Conserved motif analysis showed that all banana AQPs contained the typical AQP-like or major intrinsic protein (MIP) domain. Gene structure analysis suggested the majority of MaAQPs had two to four introns with a highly specific number and length for each subfamily. Expression analysis of MaAQP genes during fruit development and postharvest ripening showed that some MaAQP genes exhibited high expression levels during these stages, indicating the involvement of MaAQP genes in banana fruit development and ripening. Additionally, some MaAQP genes showed strong induction after stress treatment and therefore, may represent potential candidates for improving banana resistance to abiotic stress. Taken together, this study identified some excellent tissue-specific, fruit development- and ripening-dependent, and abiotic stress-responsive candidate MaAQP genes, which could lay a solid foundation for genetic improvement of banana cultivars. PMID:26307965

Characterization of aquaporin 4 protein expression and localization in tissues of the dogfish (Squalus acanthias.

Directory of Open Access Journals (Sweden)

Christopher P Cutler

2012-02-01

Full Text Available The role of aquaporin water channels in Elasmobanchs such as the dogfish Squalus acanthias is completely unknown. This investigation determines the expression and cellular and sub-cellular localization of AQP4 protein in dogfish tissues. Two polyclonal antibodies were generated (AQP4/1 and AQP4/2. Western blots using the AQP4/1 antibody showed two bands (35.5kDa and 49.5kDa in most tissues similar to mammals. Liver and rectal gland showed further bands. However, unlike in mammals, AQP4 protein was expressed in all tissues including respiratory tract and liver. The AQP4/2 antibody appeared much less specific in blots. Both antibodies were used in immunohistochemistry and showed similar cellular localizations, although the AQP4/2 antibody had a more restricted sub-cellular distribution compared to AQP4/1 and therefore appeared to be more specific. In kidney a sub-set of tubules were stained which may represent intermediate tubule segments. AQP4/1 and AQP4/2 antibodies localized to the same tubules segments in serial sections although the intensity and sub-cellular distribution were different. AQP4/2 showed a basal or basolateral membrane distribution whereas AQP4/1 was often distributed throughout the cell including the nucleus. In rectal gland and cardiac stomach AQP4 was localized to secretary tubules but again AQP/1 and AQP/2 showed different sub-cellular distributions. In gill, both antibodies stained large cells in the primary filament and secondary lamellae. Again AQP4/1 antibody stained most or all the cell including the nucleus, whereas AQP4/2 had a plasma membrane and sometimes cytoplasmic distribution. Two types of large mitochondria-rich cells are known to exist in elasmobranches, that express either Na,K ATPase or V-type ATPase. Using Na,K-ATPase and V-type ATPase antibodies, AQP4 was colocalized with these proteins using the AQP4/1 antibody. Results show AQP4 is expressed in both (and all branchial Na,K ATPase and V-type ATPase

A General Relativistic Null Hypothesis Test with Event Horizon Telescope Observations of the Black Hole Shadow in Sgr A*

Science.gov (United States)

Psaltis, Dimitrios; Özel, Feryal; Chan, Chi-Kwan; Marrone, Daniel P.

2015-12-01

The half opening angle of a Kerr black hole shadow is always equal to (5 ± 0.2)GM/Dc2, where M is the mass of the black hole and D is its distance from the Earth. Therefore, measuring the size of a shadow and verifying whether it is within this 4% range constitutes a null hypothesis test of general relativity. We show that the black hole in the center of the Milky Way, Sgr A*, is the optimal target for performing this test with upcoming observations using the Event Horizon Telescope (EHT). We use the results of optical/IR monitoring of stellar orbits to show that the mass-to-distance ratio for Sgr A* is already known to an accuracy of ∼4%. We investigate our prior knowledge of the properties of the scattering screen between Sgr A* and the Earth, the effects of which will need to be corrected for in order for the black hole shadow to appear sharp against the background emission. Finally, we explore an edge detection scheme for interferometric data and a pattern matching algorithm based on the Hough/Radon transform and demonstrate that the shadow of the black hole at 1.3 mm can be localized, in principle, to within ∼9%. All these results suggest that our prior knowledge of the properties of the black hole, of scattering broadening, and of the accretion flow can only limit this general relativistic null hypothesis test with EHT observations of Sgr A* to ≲10%.

Analysis of a lin-42/period Null Allele Implicates All Three Isoforms in Regulation of Caenorhabditis elegans Molting and Developmental Timing

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Theresa L. B. Edelman

2016-12-01

Full Text Available The Caenorhabditis elegans heterochronic gene pathway regulates the relative timing of events during postembryonic development. lin-42, the worm homolog of the circadian clock gene, period, is a critical element of this pathway. lin-42 function has been defined by a set of hypomorphic alleles that cause precocious phenotypes, in which later developmental events, such as the terminal differentiation of hypodermal cells, occur too early. A subset of alleles also reveals a significant role for lin-42 in molting; larval stages are lengthened and ecdysis often fails in these mutant animals. lin-42 is a complex locus, encoding overlapping and nonoverlapping isoforms. Although existing alleles that affect subsets of isoforms have illuminated important and distinct roles for this gene in developmental timing, molting, and the decision to enter the alternative dauer state, it is essential to have a null allele to understand all of the roles of lin-42 and its individual isoforms. To remedy this problem and discover the null phenotype, we engineered an allele that deletes the entire lin-42 protein-coding region. lin-42 null mutants are homozygously viable, but have more severe phenotypes than observed in previously characterized hypomorphic alleles. We also provide additional evidence for this conclusion by using the null allele as a base for reintroducing different isoforms, showing that each isoform can provide heterochronic and molting pathway activities. Transcript levels of the nonoverlapping isoforms appear to be under coordinate temporal regulation, despite being driven by independent promoters. The lin-42 null allele will continue to be an important tool for dissecting the functions of lin-42 in molting and developmental timing.

Comprehensive Analysis of the 16p11.2 Deletion and Null Cntnap2 Mouse Models of Autism Spectrum Disorder.

Directory of Open Access Journals (Sweden)

Daniela Brunner

Full Text Available Autism spectrum disorder comprises several neurodevelopmental conditions presenting symptoms in social communication and restricted, repetitive behaviors. A major roadblock for drug development for autism is the lack of robust behavioral signatures predictive of clinical efficacy. To address this issue, we further characterized, in a uniform and rigorous way, mouse models of autism that are of interest because of their construct validity and wide availability to the scientific community. We implemented a broad behavioral battery that included but was not restricted to core autism domains, with the goal of identifying robust, reliable phenotypes amenable for further testing. Here we describe comprehensive findings from two known mouse models of autism, obtained at different developmental stages, using a systematic behavioral test battery combining standard tests as well as novel, quantitative, computer-vision based systems. The first mouse model recapitulates a deletion in human chromosome 16p11.2, found in 1% of individuals with autism. The second mouse model harbors homozygous null mutations in Cntnap2, associated with autism and Pitt-Hopkins-like syndrome. Consistent with previous results, 16p11.2 heterozygous null mice, also known as Del(7Slx1b-Sept14Aam weighed less than wild type littermates displayed hyperactivity and no social deficits. Cntnap2 homozygous null mice were also hyperactive, froze less during testing, showed a mild gait phenotype and deficits in the three-chamber social preference test, although less robust than previously published. In the open field test with exposure to urine of an estrous female, however, the Cntnap2 null mice showed reduced vocalizations. In addition, Cntnap2 null mice performed slightly better in a cognitive procedural learning test. Although finding and replicating robust behavioral phenotypes in animal models is a challenging task, such functional readouts remain important in the development of

Radiation Hardened NULL Convention Logic Asynchronous Circuit Design

Directory of Open Access Journals (Sweden)

Liang Zhou

2015-10-01

Full Text Available This paper proposes a radiation hardened NULL Convention Logic (NCL architecture that can recover from a single event latchup (SEL or single event upset (SEU fault without deadlock or any data loss. The proposed architecture is analytically proved to be SEL resistant, and by extension, proved to be SEU resistant. The SEL/SEU resistant version of a 3-stage full-word pipelined NCL 4 × 4 unsigned multiplier was implemented using the IBM cmrf8sf 130 nm 1.2 V process at the transistor level and simulated exhaustively with SEL fault injection to validate the proposed architectures. Compared with the original version, the SEL/SEU resilient version has 1.31× speed overhead, 2.74× area overhead, and 2.79× energy per operation overhead.

Detection of Fatigue Cracks at Rivets with Self-Nulling Probe

Science.gov (United States)

Wincheski, Buzz; Fulton, Jim; Nath, Shridhar; Namkung, Min

1994-01-01

A new eddy current probe developed at NASA Langley Research Center has been used to detect small cracks at rivets in aircraft lap splices [1]. The device has earlier been used to detect isolated fatigue cracks with a minimum detectable flaw size of roughly 1/2 to 1/3 the diameter of the probe [2]. The present work shows that the detectable flaw size for cracks originating at rivets can be greatly improved upon from that of isolated flaws. The use of a rotating probe method combined with spatial filtering has been used to detect 0.18 cm EDM notches, as measured from the rivet shank, with a 1.27 cm diameter probe and to detect flaws buried under the rivet head, down to a length of 0.076 cm, using a 0.32 cm diameter probe. The Self-Nulling Electromagnetic Flaw Detector induces a high density eddy current ring in the sample under test. A ferromagnetic flux focusing lens is incorporated such that in the absence of any inhomogeneities in the material under test only a minimal magnetic field will reach the interior of the probe. A magnetometer (pickup coil) located in the center of the probe therefore registers a null voltage in the absence of material defects. When a fatigue crack or other discontinuity is present in the test article the path of the eddy currents in the material is changed. The magnetic field associated with these eddy currents then enter into the interior of the probe, producing a large output voltage across the pickup coil leads. Further

A null mutation of Hhex results in abnormal cardiac development, defective vasculogenesis and elevated Vegfa levels.

Science.gov (United States)

Hallaq, Haifa; Pinter, Emese; Enciso, Josephine; McGrath, James; Zeiss, Caroline; Brueckner, Martina; Madri, Joseph; Jacobs, Harris C; Wilson, Christine M; Vasavada, Hemaxi; Jiang, Xiaobing; Bogue, Clifford W

2004-10-01

The homeobox gene Hhex has recently been shown to be essential for normal liver, thyroid and forebrain development. Hhex(-/-) mice die by mid-gestation (E14.5) and the cause of their early demise remains unclear. Because Hhex is expressed in the developing blood islands at E7.0 in the endothelium of the developing vasculature and heart at E9.0-9.5, and in the ventral foregut endoderm at E8.5-9.0, it has been postulated to play a critical role in heart and vascular development. We show here, for the first time, that a null mutation of Hhex results in striking abnormalities of cardiac and vascular development which include: (1) defective vasculogenesis, (2) hypoplasia of the right ventricle, (3) overabundant endocardial cushions accompanied by ventricular septal defects, outflow tract abnormalities and atrio-ventricular (AV) valve dysplasia and (4) aberrant development of the compact myocardium. The dramatic enlargement of the endocardial cushions in the absence of Hhex is due to decreased apoptosis and dysregulated epithelial-mesenchymal transformation (EMT). Interestingly, vascular endothelial growth factor A (Vegfa) levels in the hearts of Hhex(-/-) mice were elevated as much as three-fold between E9.5 and E11.5, and treatment of cultured Hhex(-/-) AV explants with truncated soluble Vegfa receptor 1, sFlt-1, an inhibitor of Vegf signaling, completely abolished the excessive epithelial-mesenchymal transformation seen in the absence of Hhex. Therefore, Hhex expression in the ventral foregut endoderm and/or the endothelium is necessary for normal cardiovascular development in vivo, and one function of Hhex is to repress Vegfa levels during development.

Multilevel dysregulation of STAT3 activation in anaplastic lymphoma kinase-positive T/null-cell lymphoma

DEFF Research Database (Denmark)

Zhang, Qian; Raghunath, Puthryaveett N; Xue, Liquan

2002-01-01

Accumulating evidence indicates that expression of anaplastic lymphoma kinase (ALK), typically due to t(2;5) translocation, defines a distinct type of T/null-cell lymphoma (TCL). The resulting nucleophosmin (NPM) /ALK chimeric kinase is constitutively active and oncogenic. Downstream effector mol...

Standard Test Method for Measuring Extreme Heat-Transfer Rates from High-Energy Environments Using a Transient, Null-Point Calorimeter

CERN Document Server

American Society for Testing and Materials. Philadelphia

2008-01-01

1.1 This test method covers the measurement of the heat-transfer rate or the heat flux to the surface of a solid body (test sample) using the measured transient temperature rise of a thermocouple located at the null point of a calorimeter that is installed in the body and is configured to simulate a semi-infinite solid. By definition the null point is a unique position on the axial centerline of a disturbed body which experiences the same transient temperature history as that on the surface of a solid body in the absence of the physical disturbance (hole) for the same heat-flux input. 1.2 Null-point calorimeters have been used to measure high convective or radiant heat-transfer rates to bodies immersed in both flowing and static environments of air, nitrogen, carbon dioxide, helium, hydrogen, and mixtures of these and other gases. Flow velocities have ranged from zero (static) through subsonic to hypersonic, total flow enthalpies from 1.16 to greater than 4.65 × 101 MJ/kg (5 × 102 to greater than 2 × 104 ...

A visualization of null geodesics for the bonnor massive dipole

Directory of Open Access Journals (Sweden)

G. Andree Oliva Mercado

2015-08-01

Full Text Available In this work we simulate null geodesics for the Bonnor massive dipole metric by implementing a symbolic-numerical algorithm in Sage and Python. This program is also capable of visualizing in 3D, in principle, the geodesics for any given metric. Geodesics are launched from a common point, collectively forming a cone of light beams, simulating a solid-angle section of a point source in front of a massive object with a magnetic field. Parallel light beams also were considered, and their bending due to the curvature of the space-time was simulated.

Biological and genetic properties of the p53 null preneoplastic mammary epithelium

Science.gov (United States)

Medina, Daniel; Kittrell, Frances S.; Shepard, Anne; Stephens, L. Clifton; Jiang, Cheng; Lu, Junxuan; Allred, D. Craig; McCarthy, Maureen; Ullrich, Robert L.

2002-01-01

The absence of the tumor suppressor gene p53 confers an increased tumorigenic risk for mammary epithelial cells. In this report, we describe the biological and genetic properties of the p53 null preneoplastic mouse mammary epithelium in a p53 wild-type environment. Mammary epithelium from p53 null mice was transplanted serially into the cleared mammary fat pads of p53 wild-type BALB/c female to develop stable outgrowth lines. The outgrowth lines were transplanted for 10 generations. The outgrowths were ductal in morphology and progressed through ductal hyperplasia and ductal carcinoma in situ before invasive cancer. The preneoplastic outgrowth lines were immortal and exhibited activated telomerase activity. They are estrogen and progesterone receptor-positive, and aneuploid, and had various levels of tumorigenic potential. The biological and genetic properties of these lines are distinct from those found in most hyperplastic alveolar outgrowth lines, the form of mammary preneoplasia occurring in most traditional models of murine mammary tumorigenesis. These results indicate that the preneoplastic cell populations found in this genetically engineered model are similar in biological properties to a subset of precurser lesions found in human breast cancer and provide a unique model to identify secondary events critical for tumorigenicity and invasiveness.

Status of the Visible Nulling Coronagraph Technology Demonstration Program

Science.gov (United States)

Clampin, M.; Lyon, R.

2012-01-01

We report on the development, sensing and control of the Vacuum Nuller Testbed to realize a Visible Nulling Coronagraphy (VNC) for exoplanet detection and characterization. The VNC is one of the few approaches that works with filled, segmented and sparse or diluted-aperture telescope systems. It thus spans a range of potential future NASA telescopes and could be flown as a separate instrument on such a future mission. NASA/Goddard Space Flight Center has an established effort to develop VNC technologies, and an incremental sequence of testbeds to advance this approach and its critical technologies. We will highlight results demonstrating the achievement of our TDEM contrast milestones, and highlight the performance of our wavefront sensing and control concept.

Characterization of Aquaporin 4 Protein Expression and Localization in Tissues of the Dogfish (Squalus acanthias).

Science.gov (United States)

Cutler, Christopher P; Harmon, Sheena; Walsh, Jonathon; Burch, Kia

2012-01-01

The role of aquaporin water channels such as aquaporin 4 (Aqp4) in elasmobranchs such as the dogfish Squalus acanthias is completely unknown. This investigation set out to determine the expression and cellular and sub-cellular localization of Aqp4 protein in dogfish tissues. Two polyclonal antibodies were generated (AQP4/1 and AQP4/2) and these showed somewhat different characteristics in Western blotting and immunohistochemistry. Western blots using the AQP4/1 antibody showed two bands (35.5 and 49.5 kDa) in most tissues in a similar fashion to mammals. Liver had an additional band of 57 kDa and rectal gland two further faint bands of 37.5 and 38.5 kDa. However, unlike in mammals, Aqp4 protein was ubiquitously expressed in all tissues including gill and liver. The AQP4/2 antibody appeared much less specific in Western blots. Both antibodies were used in immunohistochemistry and showed similar cellular localizations, although the AQP4/2 antibody had a more restricted sub-cellular distribution compared to AQP4/1 and therefore appeared to be more specific for Aqp4. In kidney a sub-set of tubules were stained which may represent intermediate tubule segments (In-III-In-VI). AQP4/1 and AQP4/2 antibodies localized to the same tubules segments in serial sections although the intensity and sub-cellular distribution were different. AQP4/2 showed a basal or basolateral membrane distribution whereas AQP4/1 was often distributed throughout the whole cell including the nuclear region. In rectal gland and cardiac stomach Aqp4 was localized to secretory tubules but again AQP/1 and AQP/2 exhibited different sub-cellular distributions. In gill, both antibodies stained large cells in the primary filament and secondary lamellae. Again AQP4/1 antibody stained most or all the cell including the nucleus, whereas AQP4/2 had a plasma membrane or plasma membrane and cytoplasmic distribution. Two types of large mitochondrial rich transport cells are known to exist in elasmobranchs