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Sample records for t-tubule network increases

  1. Puerarin Facilitates T-Tubule Development of Murine Embryonic Stem Cell-Derived Cardiomyocytes

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    Lu Wang

    2014-07-01

    Full Text Available Aims: The embryonic stem cell-derived cardiomyocytes (ES-CM is one of the promising cell sources for repopulation of damaged myocardium. However, ES-CMs present immature structure, which impairs their integration with host tissue and functional regeneration. This study used murine ES-CMs as an in vitro model of cardiomyogenesis to elucidate the effect of puerarin, the main compound found in the traditional Chinese medicine the herb Radix puerariae, on t-tubule development of murine ES-CMs. Methods: Electron microscope was employed to examine the ultrastructure. The investigation of transverse-tubules (t-tubules was performed by Di-8-ANEPPS staining. Quantitative real-time PCR was utilized to study the transcript level of genes related to t-tubule development. Results: We found that long-term application of puerarin throughout cardiac differentiation improved myofibril array and sarcomeres formation, and significantly facilitated t-tubules development of ES-CMs. The transcript levels of caveolin-3, amphiphysin-2 and junctophinlin-2, which are crucial for the formation and development of t-tubules, were significantly upregulated by puerarin treatment. Furthermore, puerarin repressed the expression of miR-22, which targets to caveolin-3. Conclusion: Our data showed that puerarin facilitates t-tubule development of murine ES-CMs. This might be related to the repression of miR-22 by puerarin and upregulation of Cav3, Bin1 and JP2 transcripts.

  2. Numerical Analysis of the Effect of T-tubule Location on Calcium Transient in Ventricular Myocytes

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    George, Uduak Z.; Wang, Jun; Yu, Zeyun

    2013-01-01

    Intracellular calcium (Ca2+) signaling in cardiac myocytes is vital for proper functioning of the heart. Understanding the intracellular Ca2+ dynamics would give an insight into the functions of normal and diseased hearts. In the current study, spatiotemporal Ca2+ dynamics is investigated in ventricular myocytes by considering Ca2+ release and re-uptake via sarcolemma and transverse tubules (T-tubules), Ca2+ diffusion and buffering in the cytosol, and the blockade of Ca2+ activities associated with the sarcoplasmic reticulum. This study is carried out using a three dimensional (3D) geometric model of a branch of T-tubule extracted from the electron microscopy (EM) images of a partial ventricular myocyte. Mathematical modeling is done by using a system of partial differential equations involving Ca2+ , buffers, and membrane channels. Numerical simulation results suggest that a lack of T-tubule structure at the vicinity of the cell surface could increase the peak time of Ca2+ concentration in myocytes. The results also show that T-tubules and mobile buffers play an important role in the regulation of Ca2+ transient in ventricular myocytes. PMID:24212025

  3. Revealing t-tubules in striated muscle with new optical super-resolution microscopy techniques

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    Isuru D. Jayasinghe

    2014-12-01

    Full Text Available The t-tubular system plays a central role in the synchronisation of calcium signalling and excitation-contraction coupling in most striated muscle cells. Light microscopy has been used for imaging t-tubules for well over 100 years and together with electron microscopy (EM, has revealed the three-dimensional complexities of the t-system topology within cardiomyocytes and skeletal muscle fibres from a range of species. The emerging super-resolution single molecule localisation microscopy (SMLM techniques are offering a near 10-fold improvement over the resolution of conventional fluorescence light microscopy methods, with the ability to spectrally resolve nanometre scale distributions of multiple molecular targets. In conjunction with the next generation of electron microscopy, SMLM has allowed the visualisation and quantification of intricate t-tubule morphologies within large areas of muscle cells at an unprecedented level of detail. In this paper, we review recent advancements in the t-tubule structural biology with the utility of various microscopy techniques. We outline the technical considerations in adapting SMLM to study t-tubules and its potential to further our understanding of the molecular processes that underlie the sub-micron scale structural alterations observed in a range of muscle pathologies.

  4. Equivalent complex conductivities representing the effects of T-tubules and folded surface membranes on the electrical admittance and impedance of skeletal muscles measured by external-electrode method

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    Sekine, Katsuhisa

    2017-12-01

    In order to represent the effects of T-tubules and folded surface membranes on the electrical admittance and impedance of skeletal muscles measured by the external-electrode method, analytical relations for the equivalent complex conductivities of hypothetical smooth surface membranes were derived. In the relations, the effects of each tubule were represented by the admittance of a straight cable. The effects of the folding of a surface membrane were represented by the increased area of surface membranes. The equivalent complex conductivities were represented as summation of these effects, and the effects of the T-tubules were different between the transversal and longitudinal directions. The validity of the equivalent complex conductivities was supported by the results of finite-difference method (FDM) calculations made using three-dimensional models in which T-tubules and folded surface membranes were represented explicitly. FDM calculations using the equivalent complex conductivities suggested that the electrically inhomogeneous structure due to the existence of muscle cells with T-tubules was sufficient for explaining the experimental results previously obtained using the external-electrode method. Results of FDM calculations in which the structural changes caused by muscle contractions were taken into account were consistent with the reported experimental results.

  5. Dysferlin, annexin A1, and mitsugumin 53 are upregulated in muscular dystrophy and localize to longitudinal tubules of the T-system with stretch.

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    Waddell, Leigh B; Lemckert, Frances A; Zheng, Xi F; Tran, Jenny; Evesson, Frances J; Hawkes, Joanne M; Lek, Angela; Street, Neil E; Lin, Peihui; Clarke, Nigel F; Landstrom, Andrew P; Ackerman, Michael J; Weisleder, Noah; Ma, Jianjie; North, Kathryn N; Cooper, Sandra T

    2011-04-01

    Mutations in dysferlin cause an inherited muscular dystrophy because of defective membrane repair. Three interacting partners of dysferlin are also implicated in membrane resealing: caveolin-3 (in limb girdle muscular dystrophy type 1C), annexin A1, and the newly identified protein mitsugumin 53 (MG53). Mitsugumin 53 accumulates at sites of membrane damage, and MG53-knockout mice display a progressive muscular dystrophy. This study explored the expression and localization of MG53 in human skeletal muscle, how membrane repair proteins are modulated in various forms of muscular dystrophy, and whether MG53 is a primary cause of human muscle disease. Mitsugumin 53 showed variable sarcolemmal and/or cytoplasmic immunolabeling in control human muscle and elevated levels in dystrophic patients. No pathogenic MG53 mutations were identified in 50 muscular dystrophy patients, suggesting that MG53 is unlikely to be a common cause of muscular dystrophy in Australia. Western blot analysis confirmed upregulation of MG53, as well as of dysferlin, annexin A1, and caveolin-3 to different degrees, in different muscular dystrophies. Importantly, MG53, annexin A1, and dysferlin localize to the t-tubule network and show enriched labeling at longitudinal tubules of the t-system in overstretch. Our results suggest that longitudinal tubules of the t-system may represent sites of physiological membrane damage targeted by this membrane repair complex.

  6. Human Papillomavirus 16 Infection Induces VAP-Dependent Endosomal Tubulation.

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    Siddiqa, Abida; Massimi, Paola; Pim, David; Broniarczyk, Justyna; Banks, Lawrence

    2018-03-15

    Human papillomavirus (HPV) infection involves complex interactions with the endocytic transport machinery, which ultimately facilitates the entry of the incoming viral genomes into the trans -Golgi network (TGN) and their subsequent nuclear entry during mitosis. The endosomal pathway is a highly dynamic intracellular transport system, which consists of vesicular compartments and tubular extensions, although it is currently unclear whether incoming viruses specifically alter the endocytic machinery. In this study, using MICAL-L1 as a marker for tubulating endosomes, we show that incoming HPV-16 virions induce a profound alteration in global levels of endocytic tubulation. In addition, we also show a critical requirement for the endoplasmic reticulum (ER)-anchored protein VAP in this process. VAP plays an essential role in actin nucleation and endosome-to-Golgi transport. Indeed, the loss of VAP results in a dramatic decrease in the level of endosomal tubulation induced by incoming HPV-16 virions. This is also accompanied by a marked reduction in virus infectivity. In VAP knockdown cells, we see that the defect in virus trafficking occurs after capsid disassembly but prior to localization at the trans -Golgi network, with the incoming virion-transduced DNA accumulating in Vps29/TGN46-positive hybrid vesicles. Taken together, these studies demonstrate that infection with HPV-16 virions induces marked alterations of endocytic transport pathways, some of which are VAP dependent and required for the endosome-to-Golgi transport of the incoming viral L2/DNA complex. IMPORTANCE Human papillomavirus infectious entry involves multiple interactions with the endocytic transport machinery. In this study, we show that incoming HPV-16 virions induce a dramatic increase in endocytic tubulation. This tubulation requires ER-associated VAP, which plays a critical role in ensuring the delivery of cargoes from the endocytic compartments to the trans -Golgi network. Indeed, the loss of

  7. Clinical Importance of Morphological Appearance of Seminiferous Tubules During MicroTESE in NOA Cases

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    A. H. Haliloglu

    2005-12-01

    Full Text Available Design: Clinical study. Setting: Research Center on Infertility, Ankara University; and Urology Department. Patients: 65 men with nonobstructive azoospermia (NOA.\tInterventions: Microscopical appearance of seminiferous tubules was recorded during TESE surgery. Differing from others, the largest opaque-white in color tubules were cut and removed. When all the tubules have no discriminating appearance, randomized biopsies were obtained. Removed tissue pieces were subjected to mechanical mincing under the stereomicroscope and then enzymatic digestion processes. Using inversion microscope (x32 magnification spermatozoa were searched. Main Outcome Measures: Morphological appearance of seminiferous tubules under optical magnification, spermatozoa recovery rates and histopathological findings were compared.\tRESULTS: In cases of Sertoli cell-only syndrome (SCOS, maturation arrest, hypospermatogenesis and focal spermatogenesis TESE yielded at least one spermatozoon in 37%, 52%, 100% and 63% of the cases, respectively. When all the seminiferous tubules were homogenously swollen, histopathological diagnosis was hypospermatogenesis in 100% of the cases. Homogenously thin and transparent tubules corresponded to SCOS or maturation arrest in 90% and 10% of the cases, respectively. Mature spermatozoa recovery rates were 100% and zero in homogenously-swollen observed and homogenously-thin observed tubules, respectively. CONCLUSIONS: Present data indicate that in cases of all tubules are homogenous in appearance and none of them can be discriminated from others, using microscope has no advantage in selection of the tubuli to be removed, but randomizely selection would also be sufficient. MicroTESE significantly increases the success in NOA cases with seminiferous tubules dispersed heterogeneously.

  8. Denervation and high-fat diet reduce insulin signaling in T-tubules in skeletal muscle of living mice

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    Lauritzen, Hans P M; Ploug, Thorkil; Ai, Hua

    2008-01-01

    OBJECTIVE: Insulin stimulates muscle glucose transport by translocation of GLUT4 to sarcolemma and T-tubules. Despite muscle glucose uptake playing a major role in insulin resistance and type 2 diabetes, the temporal and spatial changes in insulin signaling and GLUT4 translocation during these co...

  9. T-tubule disruption promotes calcium alternans in failing ventricular myocytes: mechanistic insights from computational modeling.

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    Nivala, Michael; Song, Zhen; Weiss, James N; Qu, Zhilin

    2015-02-01

    In heart failure (HF), T-tubule (TT) disruption contributes to dyssynchronous calcium (Ca) release and impaired contraction, but its role in arrhythmogenesis remains unclear. In this study, we investigate the effects of TT disruption and other HF remodeling factors on Ca alternans in ventricular myocytes using computer modeling. A ventricular myocyte model with detailed spatiotemporal Ca cycling modeled by a coupled Ca release unit (CRU) network was used, in which the L-type Ca channels and the ryanodine receptor (RyR) channels were simulated by random Markov transitions. TT disruption, which removes the L-type Ca channels from the associated CRUs, results in "orphaned" RyR clusters and thus provides increased opportunity for spark-induced Ca sparks to occur. This effect combined with other HF remodeling factors promoted alternans by two distinct mechanisms: 1) for normal sarco-endoplasmic reticulum Ca ATPase (SERCA) activity, alternans was caused by both CRU refractoriness and coupling. The increased opportunity for spark-induced sparks by TT disruption combined with the enhanced CRU coupling by Ca elevation in the presence or absence of increased RyR leakiness facilitated spark synchronization on alternate beats to promote Ca alternans; 2) for down-regulated SERCA, alternans was caused by the sarcoplasmic reticulum (SR) Ca load-dependent mechanism, independent of CRU refractoriness. TT disruption and increased RyR leakiness shifted and steepened the SR Ca release-load relationship, which combines with down-regulated SERCA to promote Ca alternans. In conclusion, the mechanisms of Ca alternans for normal and down-regulated SERCA are different, and TT disruption promotes Ca alternans by both mechanisms, which may contribute to alternans at different stages of HF. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Histological and three dimensional organizations of lymphoid tubules in normal lymphoid organ of Penaeus monodon.

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    Duangsuwan, Pornsawan; Phoungpetchara, Ittipon; Tinikul, Yotsawan; Poljaroen, Jaruwan; Wanichanon, Chaitip; Sobhon, Prasert

    2008-04-01

    The normal lymphoid organ of Penaeus monodon (which tested negative for WSSV and YHV) was composed of two parts: lymphoid tubules and interstitial spaces, which were permeated with haemal sinuses filled with large numbers of haemocytes. There were three permanent types of cells present in the wall of lymphoid tubules: endothelial, stromal and capsular cells. Haemocytes penetrated the endothelium of the lymphoid tubule's wall to reside among the fixed cells. The outermost layer of the lymphoid tubule was covered by a network of fibers embedded in a PAS-positive extracellular matrix, which corresponded to a basket-like network that covered all the lymphoid tubules as visualized by a scanning electron microscope (SEM). Argyrophilic reticular fibers surrounded haemal sinuses and lymphoid tubules. Together they formed the scaffold that supported the lymphoid tubule. Using vascular cast and SEM, the three dimensional structure of the subgastric artery that supplies each lobe of the lymphoid organ was reconstructed. This artery branched into highly convoluted and blind-ending terminal capillaries, each forming the lumen of a lymphoid tubule around which haemocytes and other cells aggregated to form a cuff-like wall. Stromal cells which form part of the tubular scaffold were immunostained for vimentin. Examination of the whole-mounted lymphoid organ, immunostained for vimentin, by confocal microscopy exhibited the highly branching and convoluted lymphoid tubules matching the pattern of the vascular cast observed in SEM.

  11. Caveolin-3 is associated with the T-tubules of mature skeletal muscle fibers

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    Ralston, E; Ploug, Thorkil

    1999-01-01

    Caveolae are abundant in skeletal muscle and their coat contains a specific isoform of caveolin, caveolin-3. It has been suggested that during muscle development, caveolin-3 is associated with the T-tubules, but that in adult muscle it is found on the plasma membrane only. We have studied...... the distribution of caveolin-3 in single skeletal muscle fibers from adult rat soleus by confocal immunofluorescence and by immunogold electron microscopy. We found that caveolin-3 occurs at the highest density on the plasma membrane but is also present in the core of the fibers, at the I-band/A-band interface...

  12. Sorting Tubules Regulate Blood-Brain Barrier Transcytosis

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    Roberto Villaseñor

    2017-12-01

    Full Text Available Transcytosis across the blood-brain barrier (BBB regulates key processes of the brain, but the intracellular sorting mechanisms that determine successful receptor-mediated transcytosis in brain endothelial cells (BECs remain unidentified. Here, we used Transferrin receptor-based Brain Shuttle constructs to investigate intracellular transport in BECs, and we uncovered a pathway for the regulation of receptor-mediated transcytosis. By combining live-cell imaging and mathematical modeling in vitro with super-resolution microscopy of the BBB, we show that intracellular tubules promote transcytosis across the BBB. A monovalent construct (sFab sorted for transcytosis was localized to intracellular tubules, whereas a bivalent construct (dFab sorted for degradation formed clusters with impaired transport along tubules. Manipulating tubule biogenesis by overexpressing the small GTPase Rab17 increased dFab transport into tubules and induced its transcytosis in BECs. We propose that sorting tubules regulate transcytosis in BECs and may be a general mechanism for receptor-mediated transport across the BBB.

  13. 3D variations in human crown dentin tubule orientation: a phase-contrast microtomography study.

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    Zaslansky, Paul; Zabler, Simon; Fratzl, Peter

    2010-01-01

    Tubules dominate the microstructure of dentin, and in crowns of human teeth they are surrounded by thick mineralized peritubular cuffs of high stiffness. Here we examine the three-dimensional (3D) arrangement of tubules in relation to enamel on the buccal and lingual aspects of intact premolars and molars. Specifically we investigate the angular orientation of tubules relative to the plane of the junction of dentin with enamel (DEJ) by means of wet, non-destructive and high-resolution phase-contrast (coherent) tomography. Enamel capped dentin samples (n=16), cut from the buccal and lingual surfaces of upper and lower premolar and molar teeth, were imaged in water by high-resolution synchrotron-based phase-contrast X-ray radiography. Reconstructed 3D virtual images were co-aligned with respect to the DEJ plane. The average tubule orientation was determined at increasing distances from the DEJ, based on integrated projections onto orthogonal virtual planes. The angle and curl of the tubules were determined every 100 microm to a depth of 1.4mm beneath the DEJ. Most tubules do not extend at right angles from the DEJ. Even when they do, tubules always change their orientations substantially within the first half-millimeter zone beneath the DEJ, both on the buccal and lingual aspects of premolar and molar teeth. Tubules also tend to curl and twist within this zone. Student t-tests indicate that lower teeth seem to have greater tilts in the tubule orientations relative to the DEJ normal with an average angle of 42 degrees (+/-2.0 degrees), whereas upper teeth exhibit a smaller change of orientation, with an average of 32 degrees (+/-2.1 degrees). Tubules are a central characteristic of dentin, with important implications on how it is arranged and what the properties are. Knowing about the path that tubules follow is important for various reasons, ranging form improving control over restorative procedures to understanding or simulating the mechanical properties of teeth

  14. Solo and keratin filaments regulate epithelial tubule morphology.

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    Nishimura, Ryosuke; Kato, Kagayaki; Fujiwara, Sachiko; Ohashi, Kazumasa; Mizuno, Kensaku

    2018-04-28

    Epithelial tubules, consisting of the epithelial cell sheet with a central lumen, are the basic structure of many organs. Mechanical forces play an important role in epithelial tubulogenesis; however, little is known about the mechanisms controlling the mechanical forces during epithelial tubule morphogenesis. Solo (also known as ARHGEF40) is a RhoA-targeting guanine-nucleotide exchange factor that is involved in mechanical force-induced RhoA activation and stress fiber formation. Solo binds to keratin-8/keratin-18 (K8/K18) filaments, and this interaction plays a crucial role in mechanotransduction. In this study, we examined the roles of Solo and K8/K18 filaments in epithelial tubulogenesis using MDCK cells cultured in 3D collagen gels. Knockdown of either Solo or K18 resulted in rounder tubules with increased lumen size, indicating that Solo and K8/K18 filaments play critical roles in forming the elongated morphology of epithelial tubules. Moreover, knockdown of Solo or K18 decreased the level of diphosphorylated myosin light chain (a marker of contractile force) at the luminal and outer surfaces of tubules, suggesting that Solo and K8/K18 filaments are involved in the generation of the myosin II-mediated contractile force during epithelial tubule morphogenesis. In addition, K18 filaments were normally oriented along the long axis of the tubule, but knockdown of Solo perturbed their orientation. These results suggest that Solo plays crucial roles in forming the elongated morphology of epithelial tubules and in regulating myosin II activity and K18 filament organization during epithelial tubule formation.

  15. Ankyrin-B coordinates the Na/K ATPase, Na/Ca exchanger, and InsP3 receptor in a cardiac T-tubule/SR microdomain.

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    2005-12-01

    Full Text Available We report identification of an ankyrin-B-based macromolecular complex of Na/K ATPase (alpha 1 and alpha 2 isoforms, Na/Ca exchanger 1, and InsP3 receptor that is localized in cardiomyocyte T-tubules in discrete microdomains distinct from classic dihydropyridine receptor/ryanodine receptor "dyads." E1425G mutation of ankyrin-B, which causes human cardiac arrhythmia, also blocks binding of ankyrin-B to all three components of the complex. The ankyrin-B complex is markedly reduced in adult ankyrin-B(+/- cardiomyocytes, which may explain elevated [Ca2+]i transients in these cells. Thus, loss of the ankyrin-B complex provides a molecular basis for cardiac arrhythmia in humans and mice. T-tubule-associated ankyrin-B, Na/Ca exchanger, and Na/K ATPase are not present in skeletal muscle, where ankyrin-B is expressed at 10-fold lower levels than in heart. Ankyrin-B also is not abundantly expressed in smooth muscle. We propose that the ankyrin-B-based complex is a specialized adaptation of cardiomyocytes with a role for cytosolic Ca2+ modulation.

  16. Effects of vasopressin on the isolated perfused human collecting tubule.

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    Yanagawa, N; Trizna, W; Bar-Khayim, Y; Fine, L G

    1981-05-01

    Cortical collecting tubules (CCT) were dissected from the surviving normal tissue of human kidneys removed at operation for either carcinoma or calculus. These CCT's were perfused in vitro shortly after the nephrectomy was performed. Transtubular potential differences in different tubules varied from +3.2 to -2.0 mV and were reduced towards zero by lowering the temperature or by adding ouabain to the bath. In the absence of vasopressin, tubules were essentially impermeable to water with extremely low net water fluxes even in the presence of a transtubular osmotic gradient. Addition of vasopressin to the bath caused the transtubular osmotic water permeability coefficient to increase to values of 125, 175, and 155 X 10(-4) cm/sec in three tubules thus studied. These results demonstrate close similarities between the human CCT and the more extensively studied rabbit CCT.

  17. Magnetic properties of permalloy-coated organic tubules

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    Krebs, J. J.; Rubinstein, M.; Lubitz, P.; Harford, M. Z.; Baral, S.; Shashidar, R.; Ho, Y. S.; Chow, G. M.; Qadri, S.

    1991-11-01

    An initial investigation is presented of the ferromagnetic properties of a novel type of magnetic composite, viz., permalloy-coated submicron diameter hollow cylinders or tubules. The tubules form spontaneously from an organic material, a diacetylenic phosopholipid, and were used as templates on which the ferromagnetic material was deposited by electroless deposition. The permalloy-coated tubules were dispersed in an epoxy matrix to measure the magnetization and ferromagnetic resonance (FMR) properties of individual tubules. The nature of the magnetic anisotropy and the FMR spectra observed confirmed that the tubules are well aligned by a magnetic field during the epoxy curing. The FMR spectra are interpreted in terms of a powder pattern distribution of thin-film spectra consistent with the large diameter-to-thickness ratio.

  18. Transport of Streptococcus pneumoniae capsular polysaccharide in MHC Class II tubules.

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    Tom Li Stephen

    2007-03-01

    Full Text Available Bacterial capsular polysaccharides are virulence factors and are considered T cell-independent antigens. However, the capsular polysaccharide Sp1 from Streptococcus pneumoniae serotype 1 has been shown to activate CD4(+ T cells in a major histocompatibility complex (MHC class II-dependent manner. The mechanism of carbohydrate presentation to CD4(+ T cells is unknown. We show in live murine dendritic cells (DCs that Sp1 translocates from lysosomal compartments to the plasma membrane in MHCII-positive tubules. Sp1 cell surface presentation results in reduction of self-peptide presentation without alteration of the MHCII self peptide repertoire. In DM-deficient mice, retrograde transport of Sp1/MHCII complexes resulting in T cell-dependent immune responses to the polysaccharide in vitro and in vivo is significantly reduced. The results demonstrate the capacity of a bacterial capsular polysaccharide antigen to use DC tubules as a vehicle for its transport as an MHCII/saccharide complex to the cell surface for the induction of T cell activation. Furthermore, retrograde transport requires the functional role of DM in self peptide-carbohydrate exchange. These observations open new opportunities for the design of vaccines against microbial encapsulated pathogens.

  19. Dentinal tubules revealed with X-ray tensor tomography.

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    Jud, Christoph; Schaff, Florian; Zanette, Irene; Wolf, Johannes; Fehringer, Andreas; Pfeiffer, Franz

    2016-09-01

    Dentin is a mineralized material making up most of the tooth bulk. A system of microtubules, so called dentinal tubules, transverses it radially from the pulp chamber to the outside. This highly oriented structure leads to anisotropic mechanical properties directly connected to the tubules orientation and density: the ultimate tensile strength as well as the fracture toughness and the shear strength are largest perpendicular to dentinal tubules. Consequently, the fatigue strength depends on the direction of dentinal tubules, too. However, none of the existing techniques used to investigate teeth provide access to orientation and density of dentinal tubules for an entire specimen in a non-destructive way. In this paper, we measure a third molar human tooth both with conventional micro-CT and X-ray tensor tomography (XTT). While the achievable resolution in micro-CT is too low to directly resolve the dentinal tubules, we provide strong evidence that the direction and density of dentinal tubules can be indirectly measured by XTT, which exploits small-angle X-ray scattering to retrieve a 3D map of scattering tensors. We show that the mean directions of scattering structures correlate to the orientation of dentinal tubules and that the mean effective scattering strength provides an estimation of the relative density of dentinal tubules. Thus, this method could be applied to investigate the connection between tubule orientation and fatigue or tensile properties of teeth for a full sample without cutting one, non-representative peace of tooth out of the full sample. Copyright © 2016 The Academy of Dental Materials. All rights reserved.

  20. Approach of the T-CONT Allocation to Increase the Bandwidth in Passive Optical Networks

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    Z. Bosternak

    2017-12-01

    Full Text Available This paper works with the simulation of T-CONT allocation and delay analysis in passive optical networks PON. Building our networks with the PON technology we can achieve increased data rates, however we need to ensure that the idle gaps between the particular transmissions are minimal. The primary method for the upstream time slot allocation in passive optical networks is via Multi Point Control Protocol. The baseline standard of this protocol clearly defines the use of the REPORT and GATE control messages. The two optical network elements used here, the optical network unit ONT and the optical line termination OLT, located at the central office CO, can be scheduled to allocate the time slots. Using the control messages, a more accurate scheduling algorithm can be developed, hence we can directly improve the utilization of the bandwidth as well. In this work, we introduce the basic topology of the passive optical networks, how PON works and what basic principles of bandwidth allocation have been applied. Subsequently, we suggest a selection of methods for time slot allocation and we make an analysis on the achieved results. Our main focus is on the system load, transfer delay and the analysis of the effectivity.

  1. Wild boars (Sus scrofa scrofa seminiferous tubules morphometry

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    Deiler Sampaio Costa

    2006-09-01

    Full Text Available The aim of this data was to analyze morphology and function of the seminiferous tubule in adult wild boars. Testes removed by unilateral castration of five animals were used. The testicular parenchyma was composed by 82.1±2.2% of seminiferous tubule and 17.9±2.2% of intertubular tissue. The tubular diameter was 249.2±33.0 µm and the seminiferous tubule lenght per gram of testis was 19.3±4.9m. The spermatogonial mitoses efficiency coefficient, meiotic index and spermatogenesis efficiency were 10.34, 2.71 and 30.5 respectively. Each Sertoli cell supported about 13 germinatives cells. The hystometric parameters studied were very similar to those related for domestic boars, however, the wild boars intrinsic efficiency of spermatogenesis and Sertoli cells indexes were smaller than in domestic boars.Objetivou-se com esta pesquisa estudar as características morfométricas e funcionais dos túbulos seminíferos de javalis adultos. Utilizaram-se testículos de cinco animais submetidos a orquiectomia unilateral. O parênquima testicular foi composto por 82,1 ± 2,2% de túbulos seminíferos e 17,9 ± 2,2% de tecido intertubular. O diâmetro tubular foi de 249,2 ± 33,0µm e o comprimento dos túbulos seminíferos por grama de testículo foi de 19,3 ± 4,9m. O coeficiente de eficiência das mitoses espermatogônias, o rendimento meiótico e o rendimento geral da espermatogênese foram, respectivamente, 10,34, 2,71 e 30,50. Cada célula de Sértoli suportou cerca de 13 células germinativas. Conclui-se que os parâmetros histométricos estudados nesta pesquisa foram muito semelhantes aos valores relatados para suínos domésticos, entretanto, o rendimento intrínseco da espermatogênese e os índices de células de Sértoli de javalis foram relativamente baixos quando comparados com aqueles animais.

  2. Colchicine Depolymerizes Microtubules, Increases Junctophilin-2, and Improves Right Ventricular Function in Experimental Pulmonary Arterial Hypertension.

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    Prins, Kurt W; Tian, Lian; Wu, Danchen; Thenappan, Thenappan; Metzger, Joseph M; Archer, Stephen L

    2017-05-31

    Pulmonary arterial hypertension (PAH) is a lethal disease characterized by obstructive pulmonary vascular remodeling and right ventricular (RV) dysfunction. Although RV function predicts outcomes in PAH, mechanisms of RV dysfunction are poorly understood, and RV-targeted therapies are lacking. We hypothesized that in PAH, abnormal microtubular structure in RV cardiomyocytes impairs RV function by reducing junctophilin-2 (JPH2) expression, resulting in t-tubule derangements. Conversely, we assessed whether colchicine, a microtubule-depolymerizing agent, could increase JPH2 expression and enhance RV function in monocrotaline-induced PAH. Immunoblots, confocal microscopy, echocardiography, cardiac catheterization, and treadmill testing were used to examine colchicine's (0.5 mg/kg 3 times/week) effects on pulmonary hemodynamics, RV function, and functional capacity. Rats were treated with saline (n=28) or colchicine (n=24) for 3 weeks, beginning 1 week after monocrotaline (60 mg/kg, subcutaneous). In the monocrotaline RV, but not the left ventricle, microtubule density is increased, and JPH2 expression is reduced, with loss of t-tubule localization and t-tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves t-tubule morphology in RV cardiomyocytes. Colchicine therapy diminishes RV hypertrophy, improves RV function, and enhances RV-pulmonary artery coupling. Colchicine reduces small pulmonary arteriolar thickness and improves pulmonary hemodynamics. Finally, colchicine increases exercise capacity. Monocrotaline-induced PAH causes RV-specific derangement of microtubules marked by reduction in JPH2 and t-tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves both t-tubule architecture and RV function. Colchicine also reduces adverse pulmonary vascular remodeling. These results provide biological plausibility for a clinical trial to repurpose colchicine as a RV-directed therapy for PAH

  3. Luminal uptake and intracellular transport of insulin in renal proximal tubules

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    Hellfritzsch, M.; Christensen, E.I.; Sonne, O.

    1986-01-01

    It is generally accepted that proteins taken up from the renal tubular fluid are transported into lysosomes in proximal tubule cells. Recently, however, it has been postulated that insulin in isolated perfused rat kidneys did not accumulate in lysosomes but to a certain degree in the Golgi region. The present study was undertaken to investigate the intracellular handling of biologically unaltered insulin in rat renal proximal tubule cells. Rats were prepared for in vivo micropuncture and either a colloidal gold insulin complex or insulin monoiodinated in the A-14 position ( 125 I-insulin) was microinfused into proximal tubules. After 5, 10, 25 or 60 min the tubules were fixed by microinfusion of glutaraldehyde and processed for electron microscopy or electron microscope autoradiography. A qualitative analysis of tubules infused with colloidal gold insulin or 125 I-insulin showed that insulin was taken up by endocytosis and transported to lysosomes, and a quantitative autoradiographic analysis of the 125 I-insulin microinfused tubules showed that the grain density after five min was significantly increased for endocytic vacuoles and for lysosomes. After 60 min the grain density was still significant over lysosomes. The accumulation of grains was non-significant over all other areas analyzed at any time. This study shows that insulin is taken up from the luminal side of the proximal tubule by endocytosis and transported to the lysosomes. There was no significant transport to the Golgi region

  4. Malpighian Tubules as Novel Targets for Mosquito Control

    Directory of Open Access Journals (Sweden)

    Peter M. Piermarini

    2017-01-01

    Full Text Available The Malpighian tubules and hindgut are the renal excretory tissues of mosquitoes; they are essential to maintaining hemolymph water and solute homeostasis. Moreover, they make important contributions to detoxifying metabolic wastes and xenobiotics in the hemolymph. We have focused on elucidating the molecular mechanisms of Malpighian tubule function in adult female mosquitoes and developing chemical tools as prototypes for next-generation mosquitocides that would act via a novel mechanism of action (i.e., renal failure. To date, we have targeted inward rectifier potassium (Kir channels expressed in the Malpighian tubules of the yellow fever mosquito Aedes aegypti and malaria mosquito Anopheles gambiae. Inhibition of these channels with small molecules inhibits transepithelial K+ and fluid secretion in Malpighian tubules, leading to a disruption of hemolymph K+ and fluid homeostasis in adult female mosquitoes. In addition, we have used next-generation sequencing to characterize the transcriptome of Malpighian tubules in the Asian tiger mosquito Aedes albopictus, before and after blood meals, to reveal new molecular targets for potentially disrupting Malpighian tubule function. Within 24 h after a blood meal, the Malpighian tubules enhance the mRNA expression of genes encoding mechanisms involved with the detoxification of metabolic wastes produced during blood digestion (e.g., heme, NH3, reactive oxygen species. The development of chemical tools targeting these molecular mechanisms in Malpighian tubules may offer a promising avenue for the development of mosquitocides that are highly-selective against hematophagous females, which are the only life stage that transmits pathogens.

  5. Effect of theobromine-containing toothpaste on dentin tubule occlusion in situ.

    Science.gov (United States)

    Amaechi, Bennett T; Mathews, Sapna M; Mensinkai, Poornima K

    2015-01-01

    Dentin hypersensitivity (DH) is treated by either occlusion of dentin tubules or nerve desensitization. This in situ study compared dentin tubules occlusion by theobromine-containing dentifrices with (Theodent-classic-F®, TCF) and without (Theodent-classic®, TC) fluoride with 1,500 ppm fluoride toothpaste, Colgate®-Regular (Fluoride) and Novamin®-containing toothpaste, Sensodyne®-5000-Nupro (Novamin®). Each subject wore four intraoral appliances bearing dentin blocks while using one of four test dentifrices (n = 20/dentifrice) twice daily for 7 days. The four appliances were removed successively after 1, 2, 3, and 7 days. Treated blocks and their control (untreated) blocks were examined with scanning electron microscopy (SEM). Effects were compared statistically (ANOVA/Tukey's) based on percentage of surface area covered by deposited precipitate layer (%DPL) and percentage of fully open (%FOT), partially occluded (%POT), and completely occluded (%COT) tubules in each block calculated relative to the number of tubules in their control blocks. SEM observation indicated an increased %COT and %DPL over time. After 1 and 2 days, %COT was comparable with TC and TCF, and significantly (p Theobromine-containing toothpastes with and without fluoride have equal potential in occluding dentin tubules within a shorter time period than Novamin®-containing toothpaste; however, the three demonstrated equal potential after 1 week, but not the fluoride toothpaste. Theobromine-containing toothpaste promoted dentin tubule occlusion thus shows potential to relief DH.

  6. Proteomic changes in response to crystal formation in Drosophila Malpighian tubules.

    Science.gov (United States)

    Chung, Vera Y; Konietzny, Rebecca; Charles, Philip; Kessler, Benedikt; Fischer, Roman; Turney, Benjamin W

    2016-04-02

    Kidney stone disease is a major health burden with a complex and poorly understood pathophysiology. Drosophila Malpighian tubules have been shown to resemble human renal tubules in their physiological function. Herein, we have used Drosophila as a model to study the proteomic response to crystal formation induced by dietary manipulation in Malpighian tubules. Wild-type male flies were reared in parallel groups on standard medium supplemented with lithogenic agents: control, Sodium Oxalate (NaOx) and Ethylene Glycol (EG). Malpighian tubules were dissected after 2 weeks to visualize crystals with polarized light microscopy. The parallel group was dissected for protein extraction. A new method of Gel Assisted Sample Preparation (GASP) was used for protein extraction. Differentially abundant proteins (p<0.05) were identified by label-free quantitative proteomic analysis in flies fed with NaOx and EG diet compared with control. Their molecular functions were further screened for transmembrane ion transporter, calcium or zinc ion binder. Among these, 11 candidate proteins were shortlisted in NaOx diet and 16 proteins in EG diet. We concluded that GASP is a proteomic sample preparation method that can be applied to individual Drosophila Malpighian tubules. Our results may further increase the understanding of the pathophysiology of human kidney stone disease.

  7. Regulation of proximal tubule vacuolar H+-ATPase by PKA and AMP-activated protein kinase

    Science.gov (United States)

    Al-bataineh, Mohammad M.; Gong, Fan; Marciszyn, Allison L.; Myerburg, Michael M.

    2014-01-01

    The vacuolar H+-ATPase (V-ATPase) mediates ATP-driven H+ transport across membranes. This pump is present at the apical membrane of kidney proximal tubule cells and intercalated cells. Defects in the V-ATPase and in proximal tubule function can cause renal tubular acidosis. We examined the role of protein kinase A (PKA) and AMP-activated protein kinase (AMPK) in the regulation of the V-ATPase in the proximal tubule as these two kinases coregulate the V-ATPase in the collecting duct. As the proximal tubule V-ATPases have different subunit compositions from other nephron segments, we postulated that V-ATPase regulation in the proximal tubule could differ from other kidney tubule segments. Immunofluorescence labeling of rat ex vivo kidney slices revealed that the V-ATPase was present in the proximal tubule both at the apical pole, colocalizing with the brush-border marker wheat germ agglutinin, and in the cytosol when slices were incubated in buffer alone. When slices were incubated with a cAMP analog and a phosphodiesterase inhibitor, the V-ATPase accumulated at the apical pole of S3 segment cells. These PKA activators also increased V-ATPase apical membrane expression as well as the rate of V-ATPase-dependent extracellular acidification in S3 cell monolayers relative to untreated cells. However, the AMPK activator AICAR decreased PKA-induced V-ATPase apical accumulation in proximal tubules of kidney slices and decreased V-ATPase activity in S3 cell monolayers. Our results suggest that in proximal tubule the V-ATPase subcellular localization and activity are acutely coregulated via PKA downstream of hormonal signals and via AMPK downstream of metabolic stress. PMID:24553431

  8. Strontium effects on root dentin tubule occlusion and nanomechanical properties.

    Science.gov (United States)

    Saeki, Kuniko; Marshall, Grayson W; Gansky, Stuart A; Parkinson, Charles R; Marshall, Sally J

    2016-02-01

    Dentin hypersensitivity often is treated by promotion of dentin tubule occlusion. In this in vitro study we evaluated nanomechanical properties and degree of tubule occlusion conferred to sound and demineralized human root dentin following treatment with a 10% (w/w) strontium acetate solution and its relation to the treatment duration and delivery method. 24 human cervical root dentin disks (8 groups of 3) were polished through 0.25 μm. 12 disks were subjected to an acid challenge (1% citric acid, pH 3.8) for 2 min. The specimens were incubated in artificial saliva, treated by soaking or brushing with deionized (DI) water or a solution of 10% strontium acetate for 2 min twice a day for 28 days. The occlusion percent and nanomechanical properties were determined at the baseline, 5, 14 and 28 days. Cross-sectioned specimens were prepared to evaluate the depth affected by strontium acetate / dentin interaction by SEM. Statistical analysis was performed using linear mixed effects models. A 10% strontium acetate treatment over 5-28 days significantly increased tubule occlusion for normal root dentin and to a lesser extent for demineralized dentin and increased the AFM based nanomechanical properties of demineralized dentin. Brushing was more effective than soaking in recovery of properties of demineralized dentin when treated with strontium. No difference in tubuleocclusion was found between the two delivery methods. Strontium acetate itself proved to have the ability to occlude dentin tubules and result in small changes in the mechanical properties of dentin. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  9. Cyclophilin B expression in renal proximal tubules of hypertensive rats.

    Science.gov (United States)

    Kainer, D B; Doris, P A

    2000-04-01

    Rat cyclophilin-like protein (Cy-LP) is a candidate hypertension gene initially identified by differential hybridization and implicated in renal mechanisms of salt retention and high blood pressure. We report the molecular characterization of rat cyclophilin B (CypB) and demonstrate, through sequence analysis and an allele-specific polymerase chain reaction primer assay, that CypB but not Cy-LP is expressed in rat kidney. CypB is an endoplasmic reticulum-localized prolyl-isomerase that interacts with elongation initiation factor 2-beta, an important regulator of protein translation and a central component of the endoplasmic reticulum stress response to hypoxia or ATP depletion. Active renal transport of sodium is increased in the spontaneously hypertensive rat (SHR), and there is evidence that this coincides with hypoxia and ATP depletion in the renal cortex. In the present studies we have examined expression of CypB in rat proximal tubules, which contributes to the increased renal sodium reabsorption in this model of hypertension. We report that CypB transcript abundance is significantly elevated in proximal convoluted tubules from SHR compared with the control Wistar-Kyoto strain. This upregulation occurs in weanling animals and precedes the development of hypertension, indicating that it is not a simple response to hypertension in SHR. Further, CypB expression is also higher in a proximal tubule cell line derived from SHR compared with a similar line derived from Wistar-Kyoto rats, indicating that this difference is genetically determined. No sequence differences were observed in the CypB cDNA from these 2 strains. These observations suggest that a genetically determined alteration in proximal tubules from SHR occurs that leads to increased expression of CypB. In view of evidence linking CypB to the regulation of elongation initiation factor-2, the upregulation of CypB may result from metabolic stress.

  10. Reduced Insulin Receptor Expression Enhances Proximal Tubule Gluconeogenesis.

    Science.gov (United States)

    Pandey, Gaurav; Shankar, Kripa; Makhija, Ekta; Gaikwad, Anil; Ecelbarger, Carolyn; Mandhani, Anil; Srivastava, Aneesh; Tiwari, Swasti

    2017-02-01

    Reduced insulin receptor protein levels have been reported in the kidney cortex from diabetic humans and animals. We recently reported that, targeted deletion of insulin receptor (IR) from proximal tubules (PT) resulted in hyperglycemia in non-obese mice. To elucidate the mechanism, we examined human proximal tubule cells (hPTC) and C57BL/6 mice fed with high-fat diet (HFD, 60% fat for 20 weeks). Immunoblotting revealed a significantly lower protein level of IR in HFD compare to normal chow diet (NCD). Furthermore, a blunted rise in p-AKT 308 levels in the kidney cortex of HFD mice was observed in response to acute insulin (0.75 IU/kg body weight, i.p) relative to NCD n = 8/group, P gluconeogenesis. Transcript levels of the gluconeogenic enzyme PEPCK were significantly increased in cAMP/DEXA-stimulated hPTC cells (n = 3, P gluconeogenesis and PEPCK induction was significantly attenuated in IR (siRNA) silenced hPTC (n = 3, P gluconeogenesis. Thus reduced insulin signaling of the proximal tubule may contribute to hyperglycemia in the metabolic syndrome via elevated gluconeogenesis. J. Cell. Biochem. 118: 276-285, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Minicollagen-15, a novel minicollagen isolated from Hydra, forms tubule structures in nematocysts.

    Science.gov (United States)

    Adamczyk, Patrizia; Meier, Sebastian; Gross, Thomas; Hobmayer, Bert; Grzesiek, Stephan; Bächinger, Hans Peter; Holstein, Thomas W; Ozbek, Suat

    2008-02-29

    Minicollagens constitute a family of unusually short collagen molecules isolated from cnidarians. They are restricted to the nematocyst, a cylindrical explosive organelle serving in defense and capture of prey. The nematocyst capsule contains a long tubule inside of its matrix, which is expelled and everted during an ultrafast discharge process. Here, we report the cloning and characterization of a novel minicollagen in Hydra, designated minicollagen-15 (NCol-15). NCol-15, like NCol-3 and NCol-4, shows deviations from the canonical cysteine pattern in its terminal cysteine-rich domains (CRDs). Minicollagens share common domain architectures with a central collagen sequence flanked by polyproline stretches and short N- and C-terminal CRDs. The CRDs are involved in the formation of a highly resistant cysteine network, which constitutes the basic structure of the nematocyst capsule. Unlike NCol-1, which is part of the capsule wall, NCol-15 is localized to tubules, arguing for a functional differentiation of minicollagens within the nematocyst architecture. NMR analysis of the altered C-terminal CRD of NCol-15 showed a novel disulfide-linked structure within the cysteine-containing region exhibiting similar folding kinetics and stability as the canonical CRDs. Our data provide evidence for evolutionary diversification among minicollagens, which probably facilitated alterations in the morphology of the nematocyst wall and tubule.

  12. Paracellular transport and energy utilization in the renal tubule.

    Science.gov (United States)

    Yu, Alan S L

    2017-09-01

    Paracellular transport across the tight junction is a general mechanism for transepithelial transport of solutes in epithelia, including the renal tubule. However, why paracellular transport evolved, given the existence of a highly versatile system for transcellular transport, is unknown. Recent studies have identified the paracellular channel, claudin-2, that is responsible for paracellular reabsorption of sodium in the proximal renal tubule. Knockout of claudin-2 in mice impairs proximal sodium and fluid reabsorption but is compensated by upregulation of sodium reabsorption in the loop of Henle. This occurs at the expense of increased renal oxygen consumption, hypoxia of the outer medulla and increased susceptibility to ischemic kidney injury. Paracellular transport can be viewed as a mechanism to exploit the potential energy in existing electrochemical gradients to drive passive transepithelial transport without consuming additional energy. In this way, it enhances the efficiency of energy utilization by transporting epithelia.

  13. Use of poly (amidoamine dendrimer for dentinal tubule occlusion: a preliminary study.

    Directory of Open Access Journals (Sweden)

    Tianda Wang

    Full Text Available The occlusion of dentinal tubules is an effective method to alleviate the symptoms caused by dentin hypersensitivity, a significant health problem in dentistry and daily life. The in situ mineralization within dentinal tubules is a promising treatment for dentin hypersensitivity as it induces the formation of mineral on the sensitive regions and occludes the dentinal tubules. This study was carried out to evaluate the in vitro effect of a whole generation poly(amidoamine (PAMAM dendrimer (G3.0 on dentinal tubule occlusion by inducing mineralization within dentinal tubules. Dentin discs were treated with PAMAM dendrimers using two methods, followed by the in vitro characterization using Attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR, X-ray diffraction (XRD, Field emission scanning electron microscopy (FE-SEM and Energy-Dispersive X-ray Spectroscopy (EDS. These results showed that G3.0 PAMAM dendrimers coated on dentin surface and infiltrated in dentinal tubules could induce hydroxyapatite formation and resulted in effective dentinal tubule occlusion. Moreover, crosslinked PAMAM dendrimers could induce the remineralization of demineralized dentin and thus had the potential in dentinal tubule occlusion. In this in vitro study, dentinal tubules occlusion could be achieved by using PAMAM dendrimers. This could lead to the development of a new therapeutic technique for the treatment of dentin hypersensitivity.

  14. Diglycolic acid inhibits succinate dehydrogenase activity in human proximal tubule cells leading to mitochondrial dysfunction and cell death.

    Science.gov (United States)

    Landry, Greg M; Dunning, Cody L; Conrad, Taylor; Hitt, Mallory J; McMartin, Kenneth E

    2013-08-29

    Diethylene glycol (DEG) is a solvent used in consumer products allowing the increased risk for consumer exposure. DEG metabolism produces two primary metabolites, 2-hydroxyethoxyacetic acid (2-HEAA) and diglycolic acid (DGA). DGA has been shown to be the toxic metabolite responsible for the proximal tubule cell necrosis seen in DEG poisoning. The mechanism of DGA toxicity in the proximal tubule cell is not yet known. The chemical structure of DGA is very similar to citric acid cycle intermediates. Studies were designed to assess whether its mechanism of toxicity involves disruption of cellular metabolic pathways resulting in mitochondrial dysfunction. First, DGA preferentially inhibited succinate dehydrogenase, including human kidney cell enzyme, but had no effect on other citric acid cycle enzyme activities. DGA produces a cellular ATP depletion that precedes cell death. Human proximal tubule (HPT) cells, pre-treated with increasing DGA concentrations, showed significantly decreased oxygen consumption. DGA did not increase lactate levels, indicating no effect on glycolytic activity. DGA increased reactive oxygen species (ROS) production in HPT cells in a concentration and time dependent manner. These results indicate that DGA produced proximal tubule cell dysfunction by specific inhibition of succinate dehydrogenase and oxygen consumption. Disruption of these processes results in decreased energy production and proximal tubule cell death. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Digital three-dimensional reconstruction and ultrastructure of the mouse proximal tubule

    DEFF Research Database (Denmark)

    Zhai, X.Y.; Birn, H.; Jensen, K.B.

    2003-01-01

    . In the medullary rays, these are arranged in layers outside the clusters of more superficial tubules. In contrast to rat and human kidney, no major segmental variation in the ultrastructure of the proximal tubule was identified, and no parameters enabled definition of distinct segments in this strain of mice......, detailed analyses of normal mouse kidney structure and organization are lacking. This study describes the 3D organization and ultrastructural, segmental variation of the mouse kidney proximal tubule. A total of 160 proximal tubules in three C57/BL/6J mouse kidneys were analyzed on 800 serial sections from...

  16. Novel insights on the relationship between T-tubular defects and contractile dysfunction in a mouse model of hypertrophic cardiomyopathy.

    Science.gov (United States)

    Crocini, C; Ferrantini, C; Scardigli, M; Coppini, R; Mazzoni, L; Lazzeri, E; Pioner, J M; Scellini, B; Guo, A; Song, L S; Yan, P; Loew, L M; Tardiff, J; Tesi, C; Vanzi, F; Cerbai, E; Pavone, F S; Sacconi, L; Poggesi, C

    2016-02-01

    Abnormalities of cardiomyocyte Ca(2+) homeostasis and excitation-contraction (E-C) coupling are early events in the pathogenesis of hypertrophic cardiomyopathy (HCM) and concomitant determinants of the diastolic dysfunction and arrhythmias typical of the disease. T-tubule remodelling has been reported to occur in HCM but little is known about its role in the E-C coupling alterations of HCM. Here, the role of T-tubule remodelling in the electro-mechanical dysfunction associated to HCM is investigated in the Δ160E cTnT mouse model that expresses a clinically-relevant HCM mutation. Contractile function of intact ventricular trabeculae is assessed in Δ160E mice and wild-type siblings. As compared with wild-type, Δ160E trabeculae show prolonged kinetics of force development and relaxation, blunted force-frequency response with reduced active tension at high stimulation frequency, and increased occurrence of spontaneous contractions. Consistently, prolonged Ca(2+) transient in terms of rise and duration are also observed in Δ160E trabeculae and isolated cardiomyocytes. Confocal imaging in cells isolated from Δ160E mice reveals significant, though modest, remodelling of T-tubular architecture. A two-photon random access microscope is employed to dissect the spatio-temporal relationship between T-tubular electrical activity and local Ca(2+) release in isolated cardiomyocytes. In Δ160E cardiomyocytes, a significant number of T-tubules (>20%) fails to propagate action potentials, with consequent delay of local Ca(2+) release. At variance with wild-type, we also observe significantly increased variability of local Ca(2+) transient rise as well as higher Ca(2+)-spark frequency. Although T-tubule structural remodelling in Δ160E myocytes is modest, T-tubule functional defects determine non-homogeneous Ca(2+) release and delayed myofilament activation that significantly contribute to mechanical dysfunction. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All

  17. SGLT2 Inhibitors: Glucotoxicity and Tumorigenesis Downstream the Renal Proximal Tubule?

    Science.gov (United States)

    Bertinat, Romina; Nualart, Francisco; Yáñez, Alejandro J

    2016-08-01

    At present, diabetes mellitus is the main cause of end-stage renal disease. Effective glycaemic management is the most powerful tool to delay the establishment of diabetic complications, such as diabetic kidney disease. Together with reducing blood glucose levels, new anti-diabetic agents are expected not only to control the progression but also to restore known defects of the diabetic kidney. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are promising anti-diabetic agents that reduce hyperglycaemia by impairing glucose reabsorption in proximal tubule of the kidney and increasing glucosuria. SGLT2 inhibitors have shown to reduce glucotoxicity in isolated proximal tubule cells and also to attenuate expression of markers of overall kidney damage in experimental animal models of diabetes, but the actual renoprotective effect for downstream nephron segments is still unknown and deserves further attention. Here, we briefly discuss possible undesired effects of enhanced glucosuria and albuminuria in nephron segments beyond the proximal tubule after SGLT2 inhibitor treatment, offering new lines of research to further understand the renoprotective action of these anti-diabetic agents. Strategies blocking glucose reabsorption by renal proximal tubule epithelial cells (RPTEC) may be protective for RPTEC, but downstream nephron segments will still be exposed to high glucose and albumin levels through the luminal face. The actual effect of constant enhanced glucosuria over distal nephron segments remains to be established. J. Cell. Physiol. 231: 1635-1637, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  18. Secretory NaCl and volume flow in renal tubules.

    Science.gov (United States)

    Beyenbach, K W

    1986-05-01

    This review attempts to give a retrospective survey of the available evidence concerning the secretion of NaCl and fluid in renal tubules of the vertebrate kidney. In the absence of glomerular filtration, epithelial secretory mechanisms, which to this date have not been elucidated, are responsible for the renal excretion of NaCl and water in aglomerular fish. However, proximal tubules isolated from glomerular fish kidneys of the flounder, killifish, and the shark also have the capacity to secrete NaCl and fluid. In shark proximal tubules, fluid secretion appears to be driven via secondary active transport of Cl. In another marine vertebrate, the sea snake, secretion of Na (presumably NaCl) and fluid is observed in freshwater-adapted and water-loaded animals. Proximal tubules of mammals can be made to secrete NaCl in vitro together with secretion of aryl acids. An epithelial cell line derived from dog kidney exhibits secondary active secretion of Cl when stimulated with catecholamines. Tubular secretion of NaCl and fluid may serve a variety of renal functions, all of which are considered here. The occurrence of NaCl and fluid secretion in glomerular proximal tubules of teleosts, elasmobranchs, and reptiles and in mammalian renal tissue cultures suggests that the genetic potential for NaCl secretion is present in every vertebrate kidney.

  19. Service and multimedia data transmission in IoT networks using hybrid communication devices

    Directory of Open Access Journals (Sweden)

    Saveliev Anton

    2017-01-01

    Full Text Available Employment of various protocols and technologies in IoT networks leads to the lack of module unification and increase in incompatible technical solutions. Modern IoT networks are not designed for streaming audio/video data, so their application field is limited. Also, modern IoT networks should have connection areas for devices transferring data to the Internet, and consider hardware and software specific characteristics of these devices. We offer one-size-fits-all solution for organization of IoT network, using hybrid modules. These devices provide flexibility, scalability, energy efficiency and multi-use of network for the transfer of various types of data. This approach takes into account software and hardware features of the devices used for data transmission in IoT networks, which helps to automate connecting the modules chosen by user.

  20. Epidermal growth factor decreases PEPT2 transport capacity and expression in the rat kidney proximal tubule cell line SKPT0193 cl.2

    DEFF Research Database (Denmark)

    Bravo, Silvina A; Nielsen, Carsten Uhd; Amstrup, Jan

    2004-01-01

    by studies of apical uptake of [14C]glycylsarcosine, rPepT2 mRNA levels, and immunostaining of SKPT cells with a rPEPT2-specific antibody. On the contrary, apical uptake of glucose and lysine was increased in EGF-treated cells, indicating that EGF was not acting generally to decrease apical nutrient uptake...... mechanisms in the proximal tubule cells. Our findings indicate that EGF decreases rPEPT2 expression by lowering transcription of the rat PepT2 gene or by decreasing rat PepT2 mRNA stability. Previous investigators routinely used SKPT cell culture media with a high (10 ng/ml) EGF concentration. Our study...

  1. Effect of dental materials on gluconeogenesis in rat kidney tubules

    NARCIS (Netherlands)

    Reichl, F.X.; Durner, J.; Mückter, H.; Elsenhans, B.; Forth, W.; Kunzelmann, K.H.; Hickel, R.; Spahl, W.; Hume, W.R.; Moes, G.W.

    1999-01-01

    The effect of dental composite components triethyleneglycoldimethacrylate (TEGDMA) and hydroxyethylmethacrylate (HEMA) as well as mercuric chloride (HgCl2) and methylmercury chloride (MeHgCl) on gluconeogenesis was investigated in isolated rat kidney tubules. From starved rats kidney tubules were

  2. Natural history of seminiferous tubule degeneration in Klinefelter syndrome

    DEFF Research Database (Denmark)

    Aksglaede, Lise; Wikström, Anne M; Rajpert-De Meyts, Ewa

    2006-01-01

    Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates dramatic......Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates...... summarize current knowledge on the development of the classical endocrinological and histological features of 47,XXY males from fetus to adulthood and review the literature concerning the degeneration of the seminiferous tubules in this syndrome....

  3. Plasticity of the transverse tubules following denervation and subsequent reinnervation in rat slow and fast muscle fibres.

    Science.gov (United States)

    Takekura, Hiroaki; Tamaki, Hiroyuki; Nishizawa, Tomie; Kasuga, Norikatsu

    2003-01-01

    We have studied the effects of short term denervation followed by reinnervation on the ultrastructure of the membrane systems and on the content of and distribution of key proteins involved in calcium regulation of fast-twitch (FT) extensor digitorum longus (EDL) and slow-twitch (ST) soleus (SOL) muscle fibres. Ischiadic nerve freezing resulted in total lack of neuromuscular transmission for 3 days followed by a slow recovery, but no decline in twitch force elicited by direct stimulation. The latter measurements indicate no significant atrophy within this time frame. The membrane systems of skeletal muscle fibres were visualized using Ca92+)-K3Fe(CN)6-OsO4 techniques and observed using a high voltage electron microscope. [3H]nitrendipine binding was used to detect levels of dihydropyridine receptor (DHPR) expression. The Ca2+ pumping free sarcoplasmic reticulum domains were not affected by the denervation, but the Ca2+ release domains were dramatically increased, particularly in the FT-EDL muscle fibres. The increase is evidenced by a doubling up of the areas of contacts between SR and transverse (t-) tubules, so that in place of the normal triadic arrangement, pentadic and heptadic junctions, formed by multiple interacting layers of ST and t-tubules are seen. Frequency of pentads and heptads increases and declines in parallel to the denervation and reinnervation but with a delay. Immunofluorecence and electron microscopy observations show presence of DHPR and ryanodine receptor clusters at pentads and heptads junctions. A significant (P muscle fibres indicating that overexpression of DHPRs accompanies the build up extra junctional contacts. The results indicate that denervation reversibly affects the domains of the membrane systems involved in excitation-contraction coupling.

  4. In vivo model for microbial invasion of tooth root dentinal tubules

    Directory of Open Access Journals (Sweden)

    Jane L. BRITTAN

    2016-04-01

    Full Text Available ABSTRACT Objective Bacterial penetration of dentinal tubules via exposed dentine can lead to root caries and promote infections of the pulp and root canal system. The aim of this work was to develop a new experimental model for studying bacterial invasion of dentinal tubules within the human oral cavity. Material and Methods Sections of human root dentine were mounted into lower oral appliances that were worn by four human subjects for 15 d. Roots were then fixed, sectioned, stained and examined microscopically for evidence of bacterial invasion. Levels of invasion were expressed as Tubule Invasion Factor (TIF. DNA was extracted from root samples, subjected to polymerase chain reaction amplification of 16S rRNA genes, and invading bacteria were identified by comparison of sequences with GenBank database. Results All root dentine samples with patent tubules showed evidence of bacterial cell invasion (TIF value range from 5.7 to 9.0 to depths of 200 mm or more. A spectrum of Gram-positive and Gram-negative cell morphotypes were visualized, and molecular typing identified species of Granulicatella, Streptococcus, Klebsiella, Enterobacter, Acinetobacter, and Pseudomonas as dentinal tubule residents. Conclusion A novel in vivo model is described, which provides for human root dentine to be efficiently infected by oral microorganisms. A range of bacteria were able to initially invade dentinal tubules within exposed dentine. The model will be useful for testing the effectiveness of antiseptics, irrigants, and potential tubule occluding agents in preventing bacterial invasion of dentine.

  5. A class of dynamin-like GTPases involved in the generation of the tubular ER network

    Science.gov (United States)

    Hu, Junjie; Shibata, Yoko; Zhu, Peng-Peng; Voss, Christiane; Rismanchi, Neggy; Prinz, William A.; Rapoport, Tom A.; Blackstone, Craig

    2009-01-01

    The endoplasmic reticulum (ER) consists of tubules that are shaped by the reticulons and DP1/Yop1p, but how the tubules form an interconnected network is unknown. Here, we show that mammalian atlastins, which are dynamin-like, integral membrane GTPases, interact with the tubule-shaping proteins. The atlastins localize to the tubular ER and are required for proper network formation in vivo and in vitro. Depletion of the atlastins or overexpression of dominant-negative forms inhibits tubule interconnections. The Sey1p GTPase in S. cerevisiae is likely a functional ortholog of the atlastins; it shares the same signature motifs and membrane topology and interacts genetically and physically with the tubule-shaping proteins. Cells simultaneously lacking Sey1p and a tubule-shaping protein have ER morphology defects. These results indicate that formation of the tubular ER network depends on conserved dynamin-like GTPases. Since atlastin-1 mutations cause a common form of hereditary spastic paraplegia, we suggest ER shaping defects as a novel neuropathogenic mechanism. PMID:19665976

  6. Automated tubule nuclei quantification and correlation with oncotype DX risk categories in ER+ breast cancer whole slide images

    Science.gov (United States)

    Romo-Bucheli, David; Janowczyk, Andrew; Romero, Eduardo; Gilmore, Hannah; Madabhushi, Anant

    2016-03-01

    Early stage estrogen receptor positive (ER+) breast cancer (BCa) treatment is based on the presumed aggressiveness and likelihood of cancer recurrence. The primary conundrum in treatment and management of early stage ER+ BCa is identifying which of these cancers are candidates for adjuvant chemotherapy and which patients will respond to hormonal therapy alone. This decision could spare some patients the inherent toxicity associated with adjuvant chemotherapy. Oncotype DX (ODX) and other gene expression tests have allowed for distinguishing the more aggressive ER+ BCa requiring adjuvant chemotherapy from the less aggressive cancers benefiting from hormonal therapy alone. However these gene expression tests tend to be expensive, tissue destructive and require physical shipping of tissue blocks for the test to be done. Interestingly breast cancer grade in these tumors has been shown to be highly correlated with the ODX risk score. Unfortunately studies have shown that Bloom-Richardson (BR) grade determined by pathologists can be highly variable. One of the constituent categories in BR grading is the quantification of tubules. The goal of this study was to develop a deep learning neural network classifier to automatically identify tubule nuclei from whole slide images (WSI) of ER+ BCa, the hypothesis being that the ratio of tubule nuclei to overall number of nuclei would correlate with the corresponding ODX risk categories. The performance of the tubule nuclei deep learning strategy was evaluated with a set of 61 high power fields. Under a 5-fold cross-validation, the average precision and recall measures were 0:72 and 0:56 respectively. In addition, the correlation with the ODX risk score was assessed in a set of 7513 high power fields extracted from 174 WSI, each from a different patient (At most 50 high power fields per patient study were used). The ratio between the number of tubule and non-tubule nuclei was computed for each WSI. The results suggests that for BCa

  7. Self-(Un)rolling Biopolymer Microstructures: Rings, Tubules, and Helical Tubules from the Same Material.

    Science.gov (United States)

    Ye, Chunhong; Nikolov, Svetoslav V; Calabrese, Rossella; Dindar, Amir; Alexeev, Alexander; Kippelen, Bernard; Kaplan, David L; Tsukruk, Vladimir V

    2015-07-13

    We have demonstrated the facile formation of reversible and fast self-rolling biopolymer microstructures from sandwiched active-passive, silk-on-silk materials. Both experimental and modeling results confirmed that the shape of individual sheets effectively controls biaxial stresses within these sheets, which can self-roll into distinct 3D structures including microscopic rings, tubules, and helical tubules. This is a unique example of tailoring self-rolled 3D geometries through shape design without changing the inner morphology of active bimorph biomaterials. In contrast to traditional organic-soluble synthetic materials, we utilized a biocompatible and biodegradable biopolymer that underwent a facile aqueous layer-by-layer (LbL) assembly process for the fabrication of 2D films. The resulting films can undergo reversible pH-triggered rolling/unrolling, with a variety of 3D structures forming from biopolymer structures that have identical morphology and composition. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Urinary loss of glucose, phosphate, and protein by diffusion into proximal straight tubules injured by D-serine and maleic acid

    International Nuclear Information System (INIS)

    Carone, F.A.; Nakamura, S.; Goldman, B.

    1985-01-01

    In several models of acute renal failure leakage of glomerular filtrate out of the tubule is an important pathogenetic mechanism; however, bidirectional diffusion of solute to account for certain pathophysiologic features of acute renal failure has received meager attention. Using micropuncture and clearance methods, the authors assessed sequentially leakage of solutes and inulin across proximal straight tubules (PST) injured by two nephrotoxins. In d-serine-treated rats with extensive necrosis of PST, the basis for glucosuria and tubular leakage of inulin was studied. Glucose absorption by the proximal convoluted tubule and glucose delivery to the PST were normal, but glucose delivery to the distal tubule was increased nearly 8-fold, indicating diffusion of glucose from interstitial to tubular luminal fluid across the necrotic PST. Total kidney inulin clearance was greatly reduced, but single nephron glomerular filtration rate, based on proximal convoluted tubule samples, was normal, indicating tubular loss of inulin. Urinary recovery of [ 14 C]inulin infused into tubular lumina revealed that proximal convoluted tubule and distal tubule were impermeable to inulin and that inulin diffused out of the necrotic PST. The progressive return over 6 days of tubular impermeability for inulin correlated with relining of PST with new cells. In maleic acid-treated rats the site and extent of tubular necrosis and the nature of urinary loss of solutes were studied. Microdissection revealed that maleic acid caused limited necrosis of PST which averaged 7.4% of total proximal tubular length. Increased urinary excretion of protein, phosphate, and glucose and increased tubular permeability to microinfused [ 14 C]inulin occurred with the onset of PST necrosis, and return of these abnormalities to normal correlated with the degree of cellular repair of the PST

  9. Far infrared radiation promotes rabbit renal proximal tubule cell proliferation and functional characteristics, and protects against cisplatin-induced nephrotoxicity.

    Science.gov (United States)

    Chiang, I-Ni; Pu, Yeong-Shiau; Huang, Chao-Yuan; Young, Tai-Horng

    2017-01-01

    Far infrared radiation, a subdivision of the electromagnetic spectrum, is beneficial for long-term tissue healing, anti-inflammatory effects, growth promotion, sleep modulation, acceleration of microcirculation, and pain relief. We investigated if far infrared radiation is beneficial for renal proximal tubule cell cultivation and renal tissue engineering. We observed the effects of far infrared radiation on renal proximal tubules cells, including its effects on cell proliferation, gene and protein expression, and viability. We also examined the protective effects of far infrared radiation against cisplatin, a nephrotoxic agent, using the human proximal tubule cell line HK-2. We found that daily exposure to far infrared radiation for 30 min significantly increased rabbit renal proximal tubule cell proliferation in vitro, as assessed by MTT assay. Far infrared radiation was not only beneficial to renal proximal tubule cell proliferation, it also increased the expression of ATPase Na+/K+ subunit alpha 1 and glucose transporter 1, as determined by western blotting. Using quantitative polymerase chain reaction, we found that far infrared radiation enhanced CDK5R1, GNAS, NPPB, and TEK expression. In the proximal tubule cell line HK-2, far infrared radiation protected against cisplatin-mediated nephrotoxicity by reducing apoptosis. Renal proximal tubule cell cultivation with far infrared radiation exposure resulted in better cell proliferation, significantly higher ATPase Na+/K+ subunit alpha 1 and glucose transporter 1 expression, and significantly enhanced expression of CDK5R1, GNAS, NPPB, and TEK. These results suggest that far infrared radiation improves cell proliferation and differentiation. In HK-2 cells, far infrared radiation mediated protective effects against cisplatin-induced nephrotoxicity by reducing apoptosis, as indicated by flow cytometry and caspase-3 assay.

  10. Sodium pumps in the Malpighian tubule of Rhodnius sp.

    Directory of Open Access Journals (Sweden)

    CARUSO-NEVES CELSO

    2000-01-01

    Full Text Available Malpighian tubule of Rhodnius sp. express two sodium pumps: the classical ouabain-sensitive (Na+ + K+ATPase and an ouabain-insensitive, furosemide-sensitive Na+-ATPase. In insects, 5-hydroxitryptamine is a diuretic hormone released during meals. It inhibits the (Na+ + K+ATPase and Na+ -ATPase activities indicating that these enzymes are involved in fluid secretion. Furthermore, in Rhodnius neglectus, proximal cells of Malpighian tubule exposed to hyperosmotic medium, regulate their volume through a mechanism called regulatory volume increase. This regulatory response involves inhibition of the (Na+ + K+ATPase activity that could lead to accumulation of active osmotic solute inside the cell, influx of water and return to the normal cell volume. Adenosine, a compound produced in stress conditions, also inhibits the (Na+ + K+ATPase activity. Taken together these data indicate that (Na+ + K+ATPase is a target of the regulatory mechanisms of water and ions transport responsible for homeostasis in Rhodnius sp.

  11. Cooperation of the ER-shaping proteins atlastin, lunapark, and reticulons to generate a tubular membrane network.

    Science.gov (United States)

    Wang, Songyu; Tukachinsky, Hanna; Romano, Fabian B; Rapoport, Tom A

    2016-09-13

    In higher eukaryotes, the endoplasmic reticulum (ER) contains a network of membrane tubules, which transitions into sheets during mitosis. Network formation involves curvature-stabilizing proteins, including the reticulons (Rtns), as well as the membrane-fusing GTPase atlastin (ATL) and the lunapark protein (Lnp). Here, we have analyzed how these proteins cooperate. ATL is needed to not only form, but also maintain, the ER network. Maintenance requires a balance between ATL and Rtn, as too little ATL activity or too high Rtn4a concentrations cause ER fragmentation. Lnp only affects the abundance of three-way junctions and tubules. We suggest a model in which ATL-mediated fusion counteracts the instability of free tubule ends. ATL tethers and fuses tubules stabilized by the Rtns, and transiently sits in newly formed three-way junctions. Lnp subsequently moves into the junctional sheets and forms oligomers. Lnp is inactivated by mitotic phosphorylation, which contributes to the tubule-to-sheet conversion of the ER.

  12. Mechanisms of adaptation to chronic respiratory acidosis in the rabbit proximal tubule.

    OpenAIRE

    Krapf, R

    1989-01-01

    The hyperbicarbonatemia of chronic respiratory acidosis is maintained by enhanced bicarbonate reabsorption in the proximal tubule. To investigate the cellular mechanisms involved in this adaptation, cell and luminal pH were measured microfluorometrically using (2",7')-bis(carboxyethyl)-(5,6)-carboxyfluorescein in isolated, microperfused S2 proximal convoluted tubules from control and acidotic rabbits. Chronic respiratory acidosis was induced by exposure to 10% CO2 for 52-56 h. Tubules from ac...

  13. Tubule-Derived Wnts Are Required for Fibroblast Activation and Kidney Fibrosis.

    Science.gov (United States)

    Zhou, Dong; Fu, Haiyan; Zhang, Lu; Zhang, Ke; Min, Yali; Xiao, Liangxiang; Lin, Lin; Bastacky, Sheldon I; Liu, Youhua

    2017-08-01

    Cell-cell communication via Wnt ligands is necessary in regulating embryonic development and has been implicated in CKD. Because Wnt ligands are ubiquitously expressed, the exact cellular source of the Wnts involved in CKD remains undefined. To address this issue, we generated two conditional knockout mouse lines in which Wntless (Wls), a dedicated cargo receptor that is obligatory for Wnt secretion, was selectively ablated in tubular epithelial cells or interstitial fibroblasts. Blockade of Wnt secretion by genetic deletion of Wls in renal tubules markedly inhibited myofibroblast activation and reduced renal fibrosis after unilateral ureteral obstruction. This effect associated with decreased activation of β -catenin and downstream gene expression and preserved tubular epithelial integrity. In contrast, fibroblast-specific deletion of Wls exhibited little effect on the severity of renal fibrosis after obstructive or ischemia-reperfusion injury. In vitro , incubation of normal rat kidney fibroblasts with tubule-derived Wnts promoted fibroblast proliferation and activation. Furthermore, compared with kidney specimens from patients without CKD, biopsy specimens from patients with CKD also displayed increased expression of multiple Wnt proteins, predominantly in renal tubular epithelium. These results illustrate that tubule-derived Wnts have an essential role in promoting fibroblast activation and kidney fibrosis via epithelial-mesenchymal communication. Copyright © 2017 by the American Society of Nephrology.

  14. RNA sequencing of kidney distal tubule cells reveals multiple mediators of chronic aldosterone action

    DEFF Research Database (Denmark)

    Poulsen, Søren Brandt; Limbutara, Kavee; Fenton, Robert Andrew

    2018-01-01

    The renal aldosterone-sensitive distal tubule (ASDT) is crucial for sodium reabsorption and blood pressure regulation. The ASDT consists of the late distal convoluted tubule (DCT2), connecting tubule (CNT) and collecting duct. Due to difficulties in isolating epithelial cells from the ASDT in lar...

  15. Isolation and Characterization of Adhesive Secretion from Cuvierian Tubules of Sea Cucumber Holothuria forskåli (Echinodermata: Holothuroidea

    Directory of Open Access Journals (Sweden)

    Malgorzata Baranowska

    2011-01-01

    Full Text Available The sea cucumber Holothuria forskåli possesses a specialized system called Cuvierian tubules. During mechanical stimulation white filaments (tubules are expelled and become sticky upon contact with any object. We isolated a protein with adhesive properties from protein extracts of Cuvierian tubules from H. forskåli. This protein was identified by antibodies against recombinant precollagen D which is located in the byssal threads of the mussel Mytilus galloprovincialis. To find out the optimal procedure for extraction and purification, the identified protein was isolated by several methods, including electroelution, binding to glass beads, immunoprecipitation, and gel filtration. Antibodies raised against the isolated protein were used for localization of the adhesive protein in Cuvierian tubules. Immunostaining and immunogold electron microscopical studies revealed the strongest immunoreactivity in the mesothelium; this tissue layer is involved in adhesion. Adhesion of Cuvierian tubule extracts was measured on the surface of various materials. The extracted protein showed the strongest adhesion to Teflon surface. Increased adhesion was observed in the presence of potassium and EDTA, while cadmium caused a decrease in adhesion. Addition of antibodies and trypsin abolished the adhesive properties of the extract.

  16. Future of IoT Networks: A Survey

    Directory of Open Access Journals (Sweden)

    Suk Kyu Lee

    2017-10-01

    Full Text Available The introduction of mobile devices has changed our daily lives. They enable users to obtain information even in a nomadic environment and provide information without limitations. A decade after the introduction of this technology, we are now facing the next innovation that will change our daily lives. With the introduction of the Internet of Things (IoT, our communication ability will not be restricted to only mobile devices. Rather, it will expand to all things with which we coexist. Many studies have discussed IoT-related services and platforms. However, there are only limited discussions about the IoT network. In this paper, we will thoroughly analyze the technical details about the IoT network. Based on our survey of papers, we will provide insight about the future IoT network and the crucial components that will enable it.

  17. Natural history of seminiferous tubule degeneration in Klinefelter syndrome

    DEFF Research Database (Denmark)

    Aksglaede, Lise; Wikström, Anne M; Rajpert-De Meyts, Ewa

    2006-01-01

    Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates dramatic......Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates...

  18. 50 Years of renal physiology from one man and the perfused tubule: Maurice B. Burg.

    Science.gov (United States)

    Hamilton, Kirk L; Moore, Antoni B

    2016-08-01

    Technical advancements in research techniques in science are made in slow increments. Even so, large advances from insight and hard work of an individual with a single technique can have astonishing ramifications. Here, we examine the impact of Dr. Maurice B. Burg and the isolated perfused renal tubule technique and celebrate the 50th anniversary of the publication by Dr. Burg and his colleagues of their landmark paper in the American Journal of Physiology in 1966. In this study, we have taken a scientific visualization approach to study the scientific contributions of Dr. Burg and the isolated perfused tubule preparation as determining research impact by the number of research students, postdoctoral fellows, visiting scientists, and national and international collaborators. Additionally, we have examined the research collaborations (first and second generation scientists), established the migrational visualization of the first generation scientists who worked directly with Dr. Burg, quantified the metrics indices, identified and quantified the network of coauthorship of the first generation scientists with their second generation links, and determined the citations analyses of outputs of Dr. Burg and/or his first generation collaborators as coauthors. We also review the major advances in kidney physiology that have been made with the isolated perfused tubule technique. Finally, we are all waiting for the discoveries that the isolated perfused preparation technique will bring during the next 50 years. Copyright © 2016 the American Physiological Society.

  19. Palladium nanotubes formed by lipid tubule templating and their application in ethanol electrocatalysis.

    Science.gov (United States)

    Wang, Yinan; Ma, Shenghua; Su, Yingchun; Han, Xiaojun

    2015-04-13

    Palladium nanotubes were fabricated by using lipid tubules as templates for the first time in a controlled manner. The positively charged lipid 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) was doped into lipid tubules to adsorb PdCl4 (2-) on the tubule surfaces for further reduction. The lipid tubule formation was optimized by studying the growing dynamics and ethanol/water ratio. The DOTAP-doped tubules showed pH stability from 0 to 14, which makes them ideal templates for metal plating. The Pd nanotubes are open-ended with a tunable wall thickness. They exhibited good electrocatalytic performance in ethanol. Their electrochemically active surface areas were 6.5, 10.6, and 83.2 m(2)  g(-1) for Pd nanotubes with 77, 101, and 150 nm wall thickness, respectively. These Pd nanotubes have great potential in fuel cells. The method demonstrated also opens up a way to synthesize hollow metal nanotubes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. The influence of the type of oil phase on the self-assembly process of ¿-oryzanol + ß-sitosterol tubules in organogel systems

    NARCIS (Netherlands)

    Sawalha, H.I.M.; Margry, G.; Adel, den R.; Venema, P.; Bot, A.; Flöter, E.; Linden, van der E.

    2013-01-01

    Mixtures of ¿-oryzanol and ß-sitosterol were used to structure different oils (decane, limonene, sunflower oil, castor oil and eugenol). The ¿-oryzanol and ß-sitosterol mixtures self-assemble into double-walled hollow tubules (~10 nm in diameter) in the oil phase, which aggregate to form a network

  1. Jellyfish stinging is driven by the moving front of the nematocyst's tubule

    Science.gov (United States)

    Shavit, Uri; Park, Sinwook; Piriatinskiy, Gadi; Yossifon, Gilad; Lotan, Tamar

    2017-11-01

    Nematocysts are ultra-fast stinging organelles that are utilized by the Cnidaria phylum for prey capture, defense and locomotion. They consist of a capsule and a tubule and exert high pressure and acceleration to penetrate the target organism. Previous studies report that the ejection and elongation of the tubule are driven by a buildup of osmotic potential in the capsule. We question this explanation using a microfluidic system that controls the osmotic potential by directing the tubule through oil, where no osmotic potential can develop, while keeping the capsule in water. It was found that the time needed for elongation through oil is orders of magnitude larger than through water. Our mathematical model shows that the p γGlu concentration in the tubule is higher than in the capsule and the internal pressure that develops there serves as the elongation driving force. These findings imply that modifications of the environment along the tubule route have the potential to slow down the process and reduce its impact. This may shed light on prey defense strategies, human protection against jellyfish stinging, the use of nematocysts for drug delivery and exploration of osmotic based methods for nanotubes production and elongation.

  2. T-cell movement on the reticular network.

    Science.gov (United States)

    Donovan, Graham M; Lythe, Grant

    2012-02-21

    The idea that the apparently random motion of T cells in lymph nodes is a result of movement on a reticular network (RN) has received support from dynamic imaging experiments and theoretical studies. We present a mathematical representation of the RN consisting of edges connecting vertices that are randomly distributed in three-dimensional space, and models of lymphocyte movement on such networks including constant speed motion along edges and Brownian motion, not in three-dimensions, but only along edges. The simplest model, in which a cell moves with a constant speed along edges, is consistent with mean-squared displacement proportional to time over intervals long enough to include several changes of direction. A non-random distribution of turning angles is one consequence of motion on a preformed network. Confining cell movement to a network does not, in itself, increase the frequency of cell-cell encounters. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Arginine vasopressin increases cellular free calcium concentration and adenosine 3',5'-monophosphate production in rat renal papillary collecting tubule cells in culture

    International Nuclear Information System (INIS)

    Ishikawa, S.; Okada, K.; Saito, T.

    1988-01-01

    The role of calcium (Ca) in the cellular action of arginine vasopressin (AVP) was examined in rat renal papillary collecting tubule cells in culture. AVP increased both the cellular free Ca concentration ([Ca2+]i) using fura-2, and cAMP production in a dose-dependent manner. AVP-induced cellular Ca mobilization was totally blocked by the antagonist to the antidiuretic action of AVP, and somewhat weakened by the antagonist to the vascular action of AVP. 1-Deamino-8-D-AVP (dDAVP). an antidiuretic analog of AVP, also increased [Ca2+] significantly. Cellular Ca mobilization was not obtained with cAMP, forskolin (a diterpene activator of adenylate cyclase), or phorbol-12-myristate-13-acetate. The early phase of [Ca2+]i depended on the intracellular Ca pool, since an AVP-induced rise in [Ca2+]i was obtained in cells pretreated with Ca-free medium containing 1 mM EGTA, verapamil, or cobalt, which blocked cellular Ca uptake. Also, AVP increased 45 Ca2+ influx during the initial 10 min, which initiated the sustained phase of cellular Ca mobilization. However, cellular cAMP production induced by AVP during the 10-min observation period was diminished in the cells pretreated with Ca-free medium, verapamil, or cobalt, but was still significantly higher than the basal level. This was also diminished by a high Ca concentration in medium. These results indicate that 1) AVP concomitantly regulates cellular free Ca as well as its second messenger cAMP production; 2) AVP-induced elevation of cellular free Ca is dependent on both the cellular Ca pool and extracellular Ca; and 3) there is an optimal level of extracellular Ca to modulate the AVP action in renal papillary collecting tubule cells

  4. Active ion transport in the renal proximal tubule. II. Ionic dependence of the Na pump

    OpenAIRE

    1984-01-01

    The dependence of Na pump activity on intracellular and extracellular Na+ and K+ was investigated using a suspension of rabbit cortical tubules that contained mostly (86%) proximal tubules. The ouabain- sensitive rate of respiration (QO2) was used to measure the Na pump activity of intact tubules, and the Na,K-ATPase hydrolytic activity was measured using lysed proximal tubule membranes. The dependence (K0.5) of the Na pump on intracellular Na+ was affected by the relative intracellular conce...

  5. Mammalian knock out cells reveal prominent roles for atlastin GTPases in ER network morphology

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Guohua; Zhu, Peng-Peng; Renvoisé, Benoît; Maldonado-Báez, Lymarie; Park, Seong Hee; Blackstone, Craig, E-mail: blackstc@ninds.nih.gov

    2016-11-15

    Atlastins are large, membrane-bound GTPases that participate in the fusion of endoplasmic reticulum (ER) tubules to generate the polygonal ER network in eukaryotes. They also regulate lipid droplet size and inhibit bone morphogenetic protein (BMP) signaling, though mechanisms remain unclear. Humans have three atlastins (ATL1, ATL2, and ATL3), and ATL1 and ATL3 are mutated in autosomal dominant hereditary spastic paraplegia and hereditary sensory neuropathies. Cellular investigations of atlastin orthologs in most yeast, plants, flies and worms are facilitated by the presence of a single or predominant isoform, but loss-of-function studies in mammalian cells are complicated by multiple, broadly-expressed paralogs. We have generated mouse NIH-3T3 cells lacking all three mammalian atlastins (Atl1/2/3) using CRISPR/Cas9-mediated gene knockout (KO). ER morphology is markedly disrupted in these triple KO cells, with prominent impairment in formation of three-way ER tubule junctions. This phenotype can be rescued by expression of distant orthologs from Saccharomyces cerevisiae (Sey1p) and Arabidopsis (ROOT HAIR DEFECTIVE3) as well as any one of the three human atlastins. Minimal, if any, changes are observed in the morphology of mitochondria and the Golgi apparatus. Alterations in BMP signaling and increased sensitivity to ER stress are also noted, though effects appear more modest. Finally, atlastins appear required for the proper differentiation of NIH-3T3 cells into an adipocyte-like phenotype. These findings have important implications for the pathogenesis of hereditary spastic paraplegias and sensory neuropathies associated with atlastin mutations. - Highlights: • NIH-3T3 cells lacking all three atlastin paralogs were generated using CRISPR/Cas9. • Cells lacking all atlastin GTPases exhibit far fewer 3-way ER tubule junctions. • ER morphology defects in atlastin knockout cells are rescued by distant plant and yeast orthologs. • Atlastin knock out cells also

  6. Mammalian knock out cells reveal prominent roles for atlastin GTPases in ER network morphology

    International Nuclear Information System (INIS)

    Zhao, Guohua; Zhu, Peng-Peng; Renvoisé, Benoît; Maldonado-Báez, Lymarie; Park, Seong Hee; Blackstone, Craig

    2016-01-01

    Atlastins are large, membrane-bound GTPases that participate in the fusion of endoplasmic reticulum (ER) tubules to generate the polygonal ER network in eukaryotes. They also regulate lipid droplet size and inhibit bone morphogenetic protein (BMP) signaling, though mechanisms remain unclear. Humans have three atlastins (ATL1, ATL2, and ATL3), and ATL1 and ATL3 are mutated in autosomal dominant hereditary spastic paraplegia and hereditary sensory neuropathies. Cellular investigations of atlastin orthologs in most yeast, plants, flies and worms are facilitated by the presence of a single or predominant isoform, but loss-of-function studies in mammalian cells are complicated by multiple, broadly-expressed paralogs. We have generated mouse NIH-3T3 cells lacking all three mammalian atlastins (Atl1/2/3) using CRISPR/Cas9-mediated gene knockout (KO). ER morphology is markedly disrupted in these triple KO cells, with prominent impairment in formation of three-way ER tubule junctions. This phenotype can be rescued by expression of distant orthologs from Saccharomyces cerevisiae (Sey1p) and Arabidopsis (ROOT HAIR DEFECTIVE3) as well as any one of the three human atlastins. Minimal, if any, changes are observed in the morphology of mitochondria and the Golgi apparatus. Alterations in BMP signaling and increased sensitivity to ER stress are also noted, though effects appear more modest. Finally, atlastins appear required for the proper differentiation of NIH-3T3 cells into an adipocyte-like phenotype. These findings have important implications for the pathogenesis of hereditary spastic paraplegias and sensory neuropathies associated with atlastin mutations. - Highlights: • NIH-3T3 cells lacking all three atlastin paralogs were generated using CRISPR/Cas9. • Cells lacking all atlastin GTPases exhibit far fewer 3-way ER tubule junctions. • ER morphology defects in atlastin knockout cells are rescued by distant plant and yeast orthologs. • Atlastin knock out cells also

  7. Role of CAP350 in centriolar tubule stability and centriole assembly.

    Directory of Open Access Journals (Sweden)

    Mikael Le Clech

    Full Text Available BACKGROUND: Centrioles are microtubule-based cylindrical structures composed of nine triplet tubules and are required for the formation of the centrosome, flagella and cilia. Despite theirs importance, centriole biogenesis is poorly understood. Centrosome duplication is initiated at the G1/S transition by the sequential recruitment of a set of conserved proteins under the control of the kinase Plk4. Subsequently, the procentriole is assembled by the polymerization of centriolar tubules via an unknown mechanism involving several tubulin paralogs. METHODOLOGY/PRINCIPAL FINDINGS: Here, we developed a cellular assay to study centrosome duplication and procentriole stability based on its sensitivity to the microtubule-depolymerizing drug nocodazole. By using RNA interference experiments, we show that the stability of growing procentrioles is regulated by the microtubule-stabilizing protein CAP350, independently of hSAS-6 and CPAP which initiate procentriole growth. Furthermore, our analysis reveals the critical role of centriolar tubule stability for an efficient procentriole growth. CONCLUSIONS/SIGNIFICANCE: CAP350 belongs to a new class of proteins which associate and stabilize centriolar tubules to control centriole duplication.

  8. Worst-Case Cooperative Jamming for Secure Communications in CIoT Networks.

    Science.gov (United States)

    Li, Zhen; Jing, Tao; Ma, Liran; Huo, Yan; Qian, Jin

    2016-03-07

    The Internet of Things (IoT) is a significant branch of the ongoing advances in the Internet and mobile communications. The use of a large number of IoT devices makes the spectrum scarcity problem even more serious. The usable spectrum resources are almost entirely occupied, and thus, the increasing radio access demands of IoT devices cannot be met. To tackle this problem, the Cognitive Internet of Things (CIoT) has been proposed. In a CIoT network, secondary users, i.e., sensors and actuators, can access the licensed spectrum bands provided by licensed primary users (such as telephones). Security is a major concern in CIoT networks. However, the traditional encryption method at upper layers (such as symmetric cryptography and asymmetric cryptography) may be compromised in CIoT networks, since these types of networks are heterogeneous. In this paper, we address the security issue in spectrum-leasing-based CIoT networks using physical layer methods. Considering that the CIoT networks are cooperative networks, we propose to employ cooperative jamming to achieve secrecy transmission. In the cooperative jamming scheme, a certain secondary user is employed as the helper to harvest energy transmitted by the source and then uses the harvested energy to generate an artificial noise that jams the eavesdropper without interfering with the legitimate receivers. The goal is to minimize the signal to interference plus noise ratio (SINR) at the eavesdropper subject to the quality of service (QoS) constraints of the primary traffic and the secondary traffic. We formulate the considered minimization problem into a two-stage robust optimization problem based on the worst-case Channel State Information of the Eavesdropper. By using semi-definite programming (SDP), the optimal solutions of the transmit covariance matrices can be obtained. Moreover, in order to build an incentive mechanism for the secondary users, we propose an auction framework based on the cooperative jamming scheme

  9. Hierarchically assembled DNA origami tubules with reconfigurable chirality

    International Nuclear Information System (INIS)

    Chen, Haorong; Cha, Tae-Gon; Pan, Jing; Choi, Jong Hyun

    2013-01-01

    The dynamic reconfiguration of a hierarchically assembled tubular structure is demonstrated using the DNA origami technique. Short cylindrical DNA origami monomers are synthesized and linked into elongated tubules, which can then be disassembled via toehold-mediated strand displacement. The disassembled subunits are subsequently linked into tubules of a different chirality. The reconfiguration is performed with the subunits carrying dumbbell hairpin DNA oligonucleotides or gold nanoparticles (AuNPs). The reconfiguration of higher order origami structures presented here is useful for constructing dynamic nanostructures that exceed the size limit of single DNA origami and may facilitate the study of molecular or particle interactions by tuning their relative distance and organization. (paper)

  10. Annexin IV (Xanx-4) has a functional role in the formation of pronephric tubules.

    Science.gov (United States)

    Seville, Rachel A; Nijjar, Sarbjit; Barnett, Mark W; Massé, Karine; Jones, Elizabeth A

    2002-04-01

    Vertebrate kidney organogenesis is characterised by the successive formation of the pronephros, the mesonephros and the metanephros. The pronephros is the first to form and is the functional embryonic kidney of lower vertebrates; although it is vestigial in higher vertebrates, it is a necessary precursor for the other kidney types. The Xenopus pronephros is a simple paired organ; each nephron consists of a single large glomus, one set of tubules and a single duct. The simple organisation of the pronephros and the amenability of Xenopus laevis embryos to manipulation make the Xenopus pronephros an attractive system in which to study organogenesis. It has been shown that pronephric tubules can be induced to form in presumptive ectodermal tissue by treatment with RA and activin. We have used this system in a subtractive hybridisation screen that resulted in the cloning of Xenopus laevis annexin IV (Xanx-4). Xanx-4 transcripts are specifically located to the developing pronephric tubules, and the protein to the luminal surface of these tubules. Temporal expression shows zygotic transcription is upregulated at the time of pronephric tubule specification and persists throughout pronephric development. The temporal and spatial expression pattern of Xanx-4 suggests it may have a role in pronephric tubule development. Overexpression of Xanx-4 yields no apparent phenotype, but Xanx-4 depletion, using morpholinos, produces a shortened, enlarged tubule phenotype. The phenotype observed can be rescued by co-injection of Xanx-4 mRNA. Although the function of annexins is not yet clear, studies have suggested a role for annexins in a number of cellular processes. Annexin IV has been shown to have an inhibitory role in the regulation of epithelial calcium-activated chloride ion conductance. The enlarged pronephric tubule phenotype observed may be attributed to incorrect modulation of exocytosis, membrane plasticity or ion channels and/or water homeostasis. In this study, we

  11. A Framework to Implement IoT Network Performance Modelling Techniques for Network Solution Selection.

    Science.gov (United States)

    Delaney, Declan T; O'Hare, Gregory M P

    2016-12-01

    No single network solution for Internet of Things (IoT) networks can provide the required level of Quality of Service (QoS) for all applications in all environments. This leads to an increasing number of solutions created to fit particular scenarios. Given the increasing number and complexity of solutions available, it becomes difficult for an application developer to choose the solution which is best suited for an application. This article introduces a framework which autonomously chooses the best solution for the application given the current deployed environment. The framework utilises a performance model to predict the expected performance of a particular solution in a given environment. The framework can then choose an apt solution for the application from a set of available solutions. This article presents the framework with a set of models built using data collected from simulation. The modelling technique can determine with up to 85% accuracy the solution which performs the best for a particular performance metric given a set of solutions. The article highlights the fractured and disjointed practice currently in place for examining and comparing communication solutions and aims to open a discussion on harmonising testing procedures so that different solutions can be directly compared and offers a framework to achieve this within IoT networks.

  12. A Framework to Implement IoT Network Performance Modelling Techniques for Network Solution Selection

    Directory of Open Access Journals (Sweden)

    Declan T. Delaney

    2016-12-01

    Full Text Available No single network solution for Internet of Things (IoT networks can provide the required level of Quality of Service (QoS for all applications in all environments. This leads to an increasing number of solutions created to fit particular scenarios. Given the increasing number and complexity of solutions available, it becomes difficult for an application developer to choose the solution which is best suited for an application. This article introduces a framework which autonomously chooses the best solution for the application given the current deployed environment. The framework utilises a performance model to predict the expected performance of a particular solution in a given environment. The framework can then choose an apt solution for the application from a set of available solutions. This article presents the framework with a set of models built using data collected from simulation. The modelling technique can determine with up to 85% accuracy the solution which performs the best for a particular performance metric given a set of solutions. The article highlights the fractured and disjointed practice currently in place for examining and comparing communication solutions and aims to open a discussion on harmonising testing procedures so that different solutions can be directly compared and offers a framework to achieve this within IoT networks.

  13. The Influence of Concentration and Temperature on the Formation of γ-Oryzanol + β-Sitosterol Tubules in Edible Oil Organogels.

    Science.gov (United States)

    Sawalha, Hassan; Venema, Paul; Bot, Arjen; Flöter, Eckhard; van der Linden, Erik

    2011-03-01

    The gelation process of mixtures of γ-oryzanol and sitosterol structurants in sunflower oil was studied using light scattering, rheology, and micro-scanning calorimetry (Micro-DSC). The relation between temperature and the critical aggregation concentration (CAC) of tubule formation of γ-oryzanol and sitosterol was determined using these techniques. The temperature dependence of the CAC was used to estimate the binding energy and enthalpic and entropic contribution to the tubular formation process. The binding energy calculated at the corresponding temperatures and CACs were relatively low, in order of 2 RT (4.5 kJ mol(-1)), which is in accord with the reversibility of the tubular formation process. The formation of the tubules was associated with negative (exothermic) enthalpy change (ΔH(0)) compared with positive entropy term (-T ΔS(0) >0), indicating that the aggregation into tubules is an enthalpy-driven process. The oryzanol-sitosterol ratio affected the aggregation process; solutions with ratio of (60 oryzanol-40 sitosterol) started aggregation at higher temperature compared with other ratios.

  14. Metabolism of cysteine and cysteinesulfinate in rat kidney tubules

    International Nuclear Information System (INIS)

    De La Rosa, J.; Stipanuk, M.H.

    1986-01-01

    In studies with rat hepatocytes, hypotaurine plus taurine production accounted for less than 5% of the total amount of cysteine (CYS) catabolized, whereas more than 90% of the metabolized cysteinesulfinate (CSA) was converted to taurine plus hypotaurine. Similar studies have been carried out with kidney tubules isolated from fed rats and incubated with 2 mM [1- 14 C]CYS or 25 mM [1- 14 C]CSA at 37 0 C for up to 40 min. The production of 14 CO 2 from CSA (3.1 +/- 1.3 nmol/sup ./ min -1 /sup ./ mg dry wt -1 ) was equivalent to the accumulation of N in NH 4 + plus glutamate. Substantial oxidation of CYS was observed (16 +/- 11 nmol CO 2 x min -1 x mg dry wt -1 ), but only 12% of the expected amount of N was recovered as NH 4 + plus glutamate. Accumulation of hypotaurine plus taurine was equivalent to 20% of the observed rate of 14 CO 2 production from CSA but accounted for only 2% of the observed rate of 14 CO 2 production from CYS. Addition of unlabeled CSA to incubations with varying levels of CYS had no effect on production of 14 CO 2 . Addition of 2 mM α-ketoglutarate to the incubation mixtures resulted in an increased in 14 CO 2 production from CSA to 290% of the control level but had no effect on CYS oxidation. In agreement with the authors findings for rat hepatocytes, these data suggest that most metabolism of CYS by the rat kidney tubule occurs by a CSA-independent pathway. However, in contrast to the metabolism of CSA almost entirely to taurine in the hepatocyte, kidney tubules appeared to metabolize CSA primarily by the transamination pathway

  15. Modularization of biochemical networks based on classification of Petri net t-invariants.

    Science.gov (United States)

    Grafahrend-Belau, Eva; Schreiber, Falk; Heiner, Monika; Sackmann, Andrea; Junker, Björn H; Grunwald, Stefanie; Speer, Astrid; Winder, Katja; Koch, Ina

    2008-02-08

    Structural analysis of biochemical networks is a growing field in bioinformatics and systems biology. The availability of an increasing amount of biological data from molecular biological networks promises a deeper understanding but confronts researchers with the problem of combinatorial explosion. The amount of qualitative network data is growing much faster than the amount of quantitative data, such as enzyme kinetics. In many cases it is even impossible to measure quantitative data because of limitations of experimental methods, or for ethical reasons. Thus, a huge amount of qualitative data, such as interaction data, is available, but it was not sufficiently used for modeling purposes, until now. New approaches have been developed, but the complexity of data often limits the application of many of the methods. Biochemical Petri nets make it possible to explore static and dynamic qualitative system properties. One Petri net approach is model validation based on the computation of the system's invariant properties, focusing on t-invariants. T-invariants correspond to subnetworks, which describe the basic system behavior.With increasing system complexity, the basic behavior can only be expressed by a huge number of t-invariants. According to our validation criteria for biochemical Petri nets, the necessary verification of the biological meaning, by interpreting each subnetwork (t-invariant) manually, is not possible anymore. Thus, an automated, biologically meaningful classification would be helpful in analyzing t-invariants, and supporting the understanding of the basic behavior of the considered biological system. Here, we introduce a new approach to automatically classify t-invariants to cope with network complexity. We apply clustering techniques such as UPGMA, Complete Linkage, Single Linkage, and Neighbor Joining in combination with different distance measures to get biologically meaningful clusters (t-clusters), which can be interpreted as modules. To find

  16. Modularization of biochemical networks based on classification of Petri net t-invariants

    Directory of Open Access Journals (Sweden)

    Grunwald Stefanie

    2008-02-01

    Full Text Available Abstract Background Structural analysis of biochemical networks is a growing field in bioinformatics and systems biology. The availability of an increasing amount of biological data from molecular biological networks promises a deeper understanding but confronts researchers with the problem of combinatorial explosion. The amount of qualitative network data is growing much faster than the amount of quantitative data, such as enzyme kinetics. In many cases it is even impossible to measure quantitative data because of limitations of experimental methods, or for ethical reasons. Thus, a huge amount of qualitative data, such as interaction data, is available, but it was not sufficiently used for modeling purposes, until now. New approaches have been developed, but the complexity of data often limits the application of many of the methods. Biochemical Petri nets make it possible to explore static and dynamic qualitative system properties. One Petri net approach is model validation based on the computation of the system's invariant properties, focusing on t-invariants. T-invariants correspond to subnetworks, which describe the basic system behavior. With increasing system complexity, the basic behavior can only be expressed by a huge number of t-invariants. According to our validation criteria for biochemical Petri nets, the necessary verification of the biological meaning, by interpreting each subnetwork (t-invariant manually, is not possible anymore. Thus, an automated, biologically meaningful classification would be helpful in analyzing t-invariants, and supporting the understanding of the basic behavior of the considered biological system. Methods Here, we introduce a new approach to automatically classify t-invariants to cope with network complexity. We apply clustering techniques such as UPGMA, Complete Linkage, Single Linkage, and Neighbor Joining in combination with different distance measures to get biologically meaningful clusters (t

  17. Innervation of the renal proximal convoluted tubule of the rat

    International Nuclear Information System (INIS)

    Barajas, L.; Powers, K.

    1989-01-01

    Experimental data suggest the proximal tubule as a major site of neurogenic influence on tubular function. The functional and anatomical axial heterogeneity of the proximal tubule prompted this study of the distribution of innervation sites along the early, mid, and late proximal convoluted tubule (PCT) of the rat. Serial section autoradiograms, with tritiated norepinephrine serving as a marker for monoaminergic nerves, were used in this study. Freehand clay models and graphic reconstructions of proximal tubules permitted a rough estimation of the location of the innervation sites along the PCT. In the subcapsular nephrons, the early PCT (first third) was devoid of innervation sites with most of the innervation occurring in the mid (middle third) and in the late (last third) PCT. Innervation sites were found in the early PCT in nephrons located deeper in the cortex. In juxtamedullary nephrons, innervation sites could be observed on the PCT as it left the glomerulus. This gradient of PCT innervation can be explained by the different tubulovascular relationships of nephrons at different levels of the cortex. The absence of innervation sites in the early PCT of subcapsular nephrons suggests that any influence of the renal nerves on the early PCT might be due to an effect of neurotransmitter released from renal nerves reaching the early PCT via the interstitium and/or capillaries

  18. Worst-Case Cooperative Jamming for Secure Communications in CIoT Networks

    Directory of Open Access Journals (Sweden)

    Zhen Li

    2016-03-01

    Full Text Available The Internet of Things (IoT is a significant branch of the ongoing advances in the Internet and mobile communications. Yet, the use of a large number of IoT devices can severely worsen the spectrum scarcity problem. The usable spectrum resources are almost entirely occupied, and thus, the increasing demands of radio access from IoT devices cannot be met. To tackle this problem, the Cognitive Internet of Things (CIoT has been proposed. In a CIoT network, secondary users, i.e., sensors and actuators, can access the licensed spectrum bands provided by licensed primary users (such as cellular telephones. Security is a major concern in CIoT networks. However, the traditional encryption method at upper layers (such as symmetric and asymmetric ciphers may not be suitable for CIoT networks since these networks are composed of low-profile devices. In this paper, we address the security issues in spectrum-leasing-based CIoT networks using physical layer methods. Considering that the CIoT networks are cooperative in nature, we propose to employ cooperative jamming to achieve secure transmission. In our proposed cooperative jamming scheme, a certain secondary user is employed as the helper to harvest energy transmitted by the source and then uses the harvested energy to generate an artificial noise that jams the eavesdropper without interfering with the legitimate receivers. The goal is to minimize the Signal to Interference plus Noise Ratio (SINR at the eavesdropper subject to the Quality of Service (QoS constraints of the primary traffic and the secondary traffic. We formulate the minimization problem into a two-stage robust optimization problem based on the worst-case Channel State Information of the Eavesdropper (ECSI. By using Semi-Definite Programming (SDP, the optimal solutions of the transmit covariance matrices can be obtained. Moreover, in order to build an incentive mechanism for the secondary users, we propose an auction framework based on the

  19. Dentine tubule infection and endodontic therapy implications.

    Science.gov (United States)

    Oguntebi, B R

    1994-07-01

    A critical review of the literature suggests that the microenvironment of dentinal tubules appears to favour the selection of relatively few bacterial types irrespective of the aetiology of the infection process; coronal dental caries or pulpar necrosis. These bacteria may constitute an important reservoir from which root canal infection and reinfection may occur following pulp necrosis or during and after endodontic treatment. Previous studies of this microflora have utilized microbiological culture techniques which need to be supplemented by those that allow in situ demonstration as well as identification of the bacteria. Newer treatment strategies that are designed to eliminate this microflora must include agents that can penetrate the dentinal tubules and destroy these microorganisms, since they are located in an area beyond the host defence mechanisms where they cannot be reached by systemically administered antimicrobial agents.

  20. Visualizing the origins of selfish de novo mutations in individual seminiferous tubules of human testes.

    Science.gov (United States)

    Maher, Geoffrey J; McGowan, Simon J; Giannoulatou, Eleni; Verrill, Clare; Goriely, Anne; Wilkie, Andrew O M

    2016-03-01

    De novo point mutations arise predominantly in the male germline and increase in frequency with age, but it has not previously been possible to locate specific, identifiable mutations directly within the seminiferous tubules of human testes. Using microdissection of tubules exhibiting altered expression of the spermatogonial markers MAGEA4, FGFR3, and phospho-AKT, whole genome amplification, and DNA sequencing, we establish an in situ strategy for discovery and analysis of pathogenic de novo mutations. In 14 testes from men aged 39-90 y, we identified 11 distinct gain-of-function mutations in five genes (fibroblast growth factor receptors FGFR2 and FGFR3, tyrosine phosphatase PTPN11, and RAS oncogene homologs HRAS and KRAS) from 16 of 22 tubules analyzed; all mutations have known associations with severe diseases, ranging from congenital or perinatal lethal disorders to somatically acquired cancers. These results support proposed selfish selection of spermatogonial mutations affecting growth factor receptor-RAS signaling, highlight its prevalence in older men, and enable direct visualization of the microscopic anatomy of elongated mutant clones.

  1. Small-World and Scale-Free Network Models for IoT Systems

    Directory of Open Access Journals (Sweden)

    Insoo Sohn

    2017-01-01

    Full Text Available It is expected that Internet of Things (IoT revolution will enable new solutions and business for consumers and entrepreneurs by connecting billions of physical world devices with varying capabilities. However, for successful realization of IoT, challenges such as heterogeneous connectivity, ubiquitous coverage, reduced network and device complexity, enhanced power savings, and enhanced resource management have to be solved. All these challenges are heavily impacted by the IoT network topology supported by massive number of connected devices. Small-world networks and scale-free networks are important complex network models with massive number of nodes and have been actively used to study the network topology of brain networks, social networks, and wireless networks. These models, also, have been applied to IoT networks to enhance synchronization, error tolerance, and more. However, due to interdisciplinary nature of the network science, with heavy emphasis on graph theory, it is not easy to study the various tools provided by complex network models. Therefore, in this paper, we attempt to introduce basic concepts of graph theory, including small-world networks and scale-free networks, and provide system models that can be easily implemented to be used as a powerful tool in solving various research problems related to IoT.

  2. Substrate modulation of fatty acid effects on energization and respiration of kidney proximal tubules during hypoxia/reoxygenation.

    Directory of Open Access Journals (Sweden)

    Anja Bienholz

    Full Text Available Kidney proximal tubules subjected to hypoxia/reoxygenation develop a nonesterified fatty acid-induced energetic deficit characterized by persistent partial mitochondrial deenergization that can be prevented and reversed by citric acid cycle substrates. To further assess the role of competition between fatty acids and substrates on inner membrane substrate carriers in the deenergization and the contribution to deenergization of fatty acid effects on respiratory function, digitonin-permeabilized rabbit and mouse tubules were studied using either addition of exogenous oleate after control normoxic incubation or increases of endogenous fatty acids produced by hypoxia/reoxygenation. The results demonstrated major effects of matrix oxaloacetate accumulation on succinate-supported energization and respiration and their modification by fatty acids. Improvements of energization in the presence of fatty acids by glutamate were shown to result predominantly from lowering matrix oxaloacetate rather than from amelioration of transmembrane cycling of fatty acids and uncoupling. Mouse tubules had 2.5 fold higher rates of succinate utilization, which resulted in stronger effects of oxaloacetate accumulation than rabbit tubules. Hypoxia/reoxygenation induced respiratory inhibition that was more severe for complex I-dependent substrates. Fatty acids themselves did not acutely contribute to this respiratory inhibition, but lowering them during 60 min. reoxygenation to allow recovery of ATP during that period alleviated it. These data clarify the basis for the nonesterified fatty acid-induced mitochondrial energetic deficit in kidney proximal tubules that impairs structural and functional recovery and provide insight into interactions that need to be considered in the design of substrate-based interventions to improve mitochondrial function.

  3. Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips

    Science.gov (United States)

    Homan, Kimberly A.; Kolesky, David B.; Skylar-Scott, Mark A.; Herrmann, Jessica; Obuobi, Humphrey; Moisan, Annie; Lewis, Jennifer A.

    2016-10-01

    Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand.

  4. Data on Na,K-ATPase in primary cultures of renal proximal tubule cells treated with catecholamines

    Directory of Open Access Journals (Sweden)

    Mary Taub

    2016-03-01

    Full Text Available This data article is concerned with chronic regulation of Na,K-ATPase by catecholamines. After a chronic treatment, inhibition of Na,K-ATPase activity was observed in cultures with dopamine, while a stimulation was observed in cultures treated with norepinephrine. Following a chronic incubation with guanabenz, an α adrenergic agonist, an increase in Na,K-ATPase α and β subunit mRNAs was observed. This data supports the research article entitled, “Renal proximal tubule Na, K-ATPase is controlled by CREB regulated transcriptional coactivators as well as salt inducible kinase 1” (Taub et al. 2015 [1]. Keywords: Catecholamines, Kidney, Proximal tubule, Na,K-ATPase, Chronic

  5. Deep-apical tubules: dynamic lipid-raft microdomains in the brush-border region of enterocytes

    DEFF Research Database (Denmark)

    Hansen, Gert H; Pedersen, Jens; Niels-Christiansen, Lise-Lotte

    2003-01-01

    microdomains. Deep-apical tubules were positioned close to the actin rootlets of adjacent microvilli in the terminal web region, which had a diameter of 50-100 nm, and penetrated up to 1 microm into the cytoplasm. Markers for transcytosis, IgA and the polymeric immunoglobulin receptor, as well as the resident...... lipid raft-containing compartments, but little is otherwise known about these raft microdomains. We therefore studied in closer detail apical lipid-raft compartments in enterocytes by immunogold electron microscopy and biochemical analyses. Novel membrane structures, deep-apical tubules, were visualized...... brush-border enzyme aminopeptidase N, were present in these deep-apical tubules. We propose that deep-apical tubules are a specialized lipid-raft microdomain in the brush-border region functioning as a hub in membrane trafficking at the brush border. In addition, the sensitivity to cholesterol depletion...

  6. Auto-regeneration of mice testicle seminiferous tubules due to malnutrition based on stem cells mobilization using honey

    Directory of Open Access Journals (Sweden)

    Erma Safitri

    2016-03-01

    Conclusions: Results of this study revealed a significantly different of C34 and CD45 expressions between groups, also an increase SSCs expression and testicle seminiferous tubules cells regeneration as well.

  7. Tubule urate and PAH transport: sensitivity and specificity of serum protein inhibition

    International Nuclear Information System (INIS)

    Grantham, J.J.; Kennedy, J.; Cowley, B.

    1987-01-01

    Macromolecules in rabbit serum inhibit the cellular uptake and transepithelial secretion of [ 14 C]urate and p-[ 3 H]aminohippurate ([ 3 H]PAH) in rabbit S 2 proximal tubule segments. To understand better the potential role these inhibitors may have in the regulation of renal organic anion excretion, the authors examined the specificity and relative inhibitory effects on tubule urate and PAH transport of albumin and γ-globulin, the major inhibitory proteins in rabbit serum. Native rabbit serum markedly inhibited the cellular accumulation or urate and PAH by isolated nonperfused segments. Urate and PAH transport was also inhibited by bovine serum, human serum, Cohn-fractionated rabbit albumin, and rabbit γ-globulin, but not by Cohn-fractionated bovine serum albumin. α-Lactalbumin and β-lactoglobulin, derived from milk, also inhibited urate and PAH transport, but to a lesser extent than albumin and γ-globulin. The transport inhibitory effects of proteins were independent of their binding to urate and PAH. Unidirectional influx and the steady-state intracellular accumulation of urate and PAH in suspensions of proximal tubules were decreased by rabbit serum proteins, suggesting that these inhibitors act on the external face of the cells to diminish the uptake of the organic anions. These studies indicate that the principal plasma proteins (albumin and γ-globulin) significantly inhibit urate and PAH transporters in the basolateral membranes of S 2 proximal tubules. They suggest that circulating plasma proteins that can penetrate the basement membrane of proximal tubules may directly modulate the renal excretion of urate and PAH

  8. Developmentally regulated GTP-binding protein 2 is required for stabilization of Rac1-positive membrane tubules.

    Science.gov (United States)

    Mani, Muralidharan; Lee, Unn Hwa; Yoon, Nal Ae; Yoon, Eun Hye; Lee, Byung Ju; Cho, Wha Ja; Park, Jeong Woo

    2017-11-04

    Previously we have reported that developmentally regulated GTP-binding protein 2 (DRG2) localizes on Rab5 endosomes and plays an important role in transferrin (Tfn) recycling. We here identified DRG2 as a key regulator of membrane tubule stability. At 30 min after Tfn treatment, DRG2 localized to membrane tubules which were enriched with phosphatidylinositol 4-monophosphate [PI(4)P] and did not contain Rab5. DRG2 interacted with Rac1 more strongly with GTP-bound Rac1 and tubular localization of DRG2 depended on Rac1 activity. DRG2 depletion led to destabilization of membrane tubules, while ectopic expression of DRG2 rescued the stability of the membrane tubules in DRG2-depleted cells. Our results reveal a novel mechanism for regulation of membrane tubule stability mediated by DRG2. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Optimization of Wireless Node Discovery in an IoT Network

    DEFF Research Database (Denmark)

    Vasilev, Vladislav; Iliev, Georgi; Poulkov, Vladimir

    2015-01-01

    in the decrease in discovery costs. The proposed model covers well the dynamics of the complex sensor network, such as the one that maybe employed in an Internet of Things (IoT) scenario, where nodes need to act autonomously during the communication process. We apply the Lotka-Voltera model to increase...

  10. The Leptospira outer membrane protein LipL32 induces tubulointerstitial nephritis-mediated gene expression in mouse proximal tubule cells.

    Science.gov (United States)

    Yang, Chih-Wei; Wu, Mai-Szu; Pan, Ming-Jeng; Hsieh, Wang-Ju; Vandewalle, Alain; Huang, Chiu-Ching

    2002-08-01

    Tubulointerstitial nephritis is a main renal manifestation caused by pathogenic leptospira that accumulate mostly in the proximal tubules, thereby inducing tubular injury and tubulointerstitial nephritis. To elucidate the role of leptospira outer membrane proteins in tubulointerstitial nephritis, outer membrane proteins from pathogenic Leptospira shermani and nonpathogenic Leptospira patoc extracted by Triton X-114 were administered to cultured mouse proximal tubule cells. A dose-dependent increase of monocyte chemoattractant protein-1 (MCP-1), RANTES, nitrite, and tumor necrosis factor-alpha (TNF-alpha) in the culture supernatant was observed 48 h after incubating Leptospira shermani outer membrane proteins with mouse proximal tubule cells. RT competitive-PCR experiments showed that Leptospira shermani outer membrane proteins (0.2 microg/ml) increased the expression of MCP-1, nitric oxide synthase (iNOS), RANTES, and TNF-alpha mRNA by 3.0-, 9.4-, 2.5-, and 2.5-fold, respectively, when compared with untreated cells. Outer membrane proteins extract from avirulent Leptospira patoc did not induce significant effects. The pathogenic outer membrane proteins extract contain a major component of a 32-kD lipoprotein (LipL32), which is absent in the nonpathogenic leptospira outer membrane. An antibody raised against LipL32 prevented the stimulatory effect of Leptospira shermani outer membrane proteins extract on MCP-1 and iNOS mRNA expression in cultured proximal tubule cells, whereas recombinant LipL32 significantly stimulated the expression of MCP-1 and iNOS mRNAs and augmented nuclear binding of nuclear factor-kappaB (NF-kappaB) and AP-1 transcription factors in proximal tubule cells. An antibody raised against LipL32 also blunted the effects induced by the recombinant LipL32. This study demonstrates that LipL32 is a major component of pathogenic leptospira outer membrane proteins involved in the pathogenesis of tubulointerstitial nephritis.

  11. Discrete dynamic modeling of T cell survival signaling networks

    Science.gov (United States)

    Zhang, Ranran

    2009-03-01

    Biochemistry-based frameworks are often not applicable for the modeling of heterogeneous regulatory systems that are sparsely documented in terms of quantitative information. As an alternative, qualitative models assuming a small set of discrete states are gaining acceptance. This talk will present a discrete dynamic model of the signaling network responsible for the survival and long-term competence of cytotoxic T cells in the blood cancer T-LGL leukemia. We integrated the signaling pathways involved in normal T cell activation and the known deregulations of survival signaling in leukemic T-LGL, and formulated the regulation of each network element as a Boolean (logic) rule. Our model suggests that the persistence of two signals is sufficient to reproduce all known deregulations in leukemic T-LGL. It also indicates the nodes whose inactivity is necessary and sufficient for the reversal of the T-LGL state. We have experimentally validated several model predictions, including: (i) Inhibiting PDGF signaling induces apoptosis in leukemic T-LGL. (ii) Sphingosine kinase 1 and NFκB are essential for the long-term survival of T cells in T-LGL leukemia. (iii) T box expressed in T cells (T-bet) is constitutively activated in the T-LGL state. The model has identified potential therapeutic targets for T-LGL leukemia and can be used for generating long-term competent CTL necessary for tumor and cancer vaccine development. The success of this model, and of other discrete dynamic models, suggests that the organization of signaling networks has an determining role in their dynamics. Reference: R. Zhang, M. V. Shah, J. Yang, S. B. Nyland, X. Liu, J. K. Yun, R. Albert, T. P. Loughran, Jr., Network Model of Survival Signaling in LGL Leukemia, PNAS 105, 16308-16313 (2008).

  12. Local pH domains regulate NHE3-mediated Na+ reabsorption in the renal proximal tubule

    Science.gov (United States)

    Burford, James L.; McDonough, Alicia A.; Holstein-Rathlou, Niels-Henrik; Peti-Peterdi, Janos

    2014-01-01

    The proximal tubule Na+/H+ exchanger 3 (NHE3), located in the apical dense microvilli (brush border), plays a major role in the reabsorption of NaCl and water in the renal proximal tubule. In response to a rise in blood pressure NHE3 redistributes in the plane of the plasma membrane to the base of the brush border, where NHE3 activity is reduced. This NHE3 redistribution is assumed to provoke pressure natriuresis; however, it is unclear how NHE3 redistribution per se reduces NHE3 activity. To investigate if the distribution of NHE3 in the brush border can change the reabsorption rate, we constructed a spatiotemporal mathematical model of NHE3-mediated Na+ reabsorption across a proximal tubule cell and compared the model results with in vivo experiments in rats. The model predicts that when NHE3 is localized exclusively at the base of the brush border, it creates local pH microdomains that reduce NHE3 activity by >30%. We tested the model's prediction experimentally: the rat kidney cortex was loaded with the pH-sensitive fluorescent dye BCECF, and cells of the proximal tubule were imaged in vivo using confocal fluorescence microscopy before and after an increase of blood pressure by ∼50 mmHg. The experimental results supported the model by demonstrating that a rise of blood pressure induces the development of pH microdomains near the bottom of the brush border. These local changes in pH reduce NHE3 activity, which may explain the pressure natriuresis response to NHE3 redistribution. PMID:25298526

  13. Phosphorylation of rat kidney Na-K pump at Ser938 is required for rapid angiotensin II-dependent stimulation of activity and trafficking in proximal tubule cells.

    Science.gov (United States)

    Massey, Katherine J; Li, Quanwen; Rossi, Noreen F; Keezer, Susan M; Mattingly, Raymond R; Yingst, Douglas R

    2016-02-01

    How angiotensin (ANG) II acutely stimulates the Na-K pump in proximal tubules is only partially understood, limiting insight into how ANG II increases blood pressure. First, we tested whether ANG II increases the number of pumps in plasma membranes of native rat proximal tubules under conditions of rapid activation. We found that exposure to 100 pM ANG II for 2 min, which was previously shown to increase affinity of the Na-K pump for Na and stimulate activity threefold, increased the amount of the Na-K pump in plasma membranes of native tubules by 33%. Second, we tested whether previously observed increases in phosphorylation of the Na-K pump at Ser(938) were part of the stimulatory mechanism. These experiments were carried out in opossum kidney cells, cultured proximal tubules stably coexpressing the ANG type 1 (AT1) receptor, and either wild-type or a S938A mutant of rat kidney Na-K pump under conditions found by others to stimulate activity. We found that 10 min of incubation in 10 pM ANG II stimulated activity of wild-type pumps from 2.3 to 3.5 nmol K · mg protein(-1) · min(-1) and increased the amount of the pump in the plasma membrane by 80% but had no effect on cells expressing the S938A mutant. We conclude that acute stimulation of Na-K pump activity in native rat proximal tubules includes increased trafficking to the plasma membrane and that phosphorylation at Ser(938) is part of the mechanism by which ANG II directly stimulates activity and trafficking of the rat kidney Na-K pump in opossum kidney cells.

  14. A bradykinin-potentiating peptide (BPP-10c) from Bothrops jararaca induces changes in seminiferous tubules

    Science.gov (United States)

    2013-01-01

    Background The testis-specific isoform of angiotensin-converting enzyme (tACE) is exclusively expressed in germ cells during spermatogenesis. Although the exact role of tACE in male fertility is unknown, it clearly plays a critical function in spermatogenesis. The dipeptidase domain of tACE is identical to the C-terminal catalytic domain of somatic ACE (sACE). Bradykinin potentiating peptides (BPPs) from snake venoms are the first natural sACE inhibitors described and their structure–activity relationship studies were the basis for the development of antihypertensive drugs such as captopril. In recent years, it has been showed that a number of BPPs – including BPP-10c – are able to distinguish between the N- and C-active sites of sACE, what is not applicable to captopril. Considering the similarity between tACE and sACE (and since BPPs are able to distinguish between the two active sites of sACE), the effects of the BPP-10c and captopril on the structure and function of the seminiferous epithelium were characterized in the present study. BPP-10c and captopril were administered in male Swiss mice by intraperitoneal injection (4.7 μmol/kg for 15 days) and histological sections of testes were analyzed. Classification of seminiferous tubules and stage analysis were carried out for quantitative evaluation of germ cells of the seminiferous epithelium. The blood-testis barrier (BTB) permeability and distribution of claudin-1 in the seminiferous epithelium were analyzed by hypertonic fixative method and immunohistochemical analyses of testes, respectively. Results The morphology of seminiferous tubules from animals treated with BPP-10c showed an intense disruption of the epithelium, presence of atypical multinucleated cells in the lumen and degenerated germ cells in the adluminal compartment. BPP-10c led to an increase in the number of round spermatids and total support capacity of Sertoli cell in stages I, V, VII/VIII of the seminiferous epithelium cycle, without

  15. A bradykinin-potentiating peptide (BPP-10c) from Bothrops jararaca induces changes in seminiferous tubules.

    Science.gov (United States)

    Gilio, Joyce M; Portaro, Fernanda Cv; Borella, Maria I; Lameu, Claudiana; Camargo, Antonio Cm; Alberto-Silva, Carlos

    2013-11-06

    The testis-specific isoform of angiotensin-converting enzyme (tACE) is exclusively expressed in germ cells during spermatogenesis. Although the exact role of tACE in male fertility is unknown, it clearly plays a critical function in spermatogenesis. The dipeptidase domain of tACE is identical to the C-terminal catalytic domain of somatic ACE (sACE). Bradykinin potentiating peptides (BPPs) from snake venoms are the first natural sACE inhibitors described and their structure-activity relationship studies were the basis for the development of antihypertensive drugs such as captopril. In recent years, it has been showed that a number of BPPs - including BPP-10c - are able to distinguish between the N- and C-active sites of sACE, what is not applicable to captopril. Considering the similarity between tACE and sACE (and since BPPs are able to distinguish between the two active sites of sACE), the effects of the BPP-10c and captopril on the structure and function of the seminiferous epithelium were characterized in the present study. BPP-10c and captopril were administered in male Swiss mice by intraperitoneal injection (4.7 μmol/kg for 15 days) and histological sections of testes were analyzed. Classification of seminiferous tubules and stage analysis were carried out for quantitative evaluation of germ cells of the seminiferous epithelium. The blood-testis barrier (BTB) permeability and distribution of claudin-1 in the seminiferous epithelium were analyzed by hypertonic fixative method and immunohistochemical analyses of testes, respectively. The morphology of seminiferous tubules from animals treated with BPP-10c showed an intense disruption of the epithelium, presence of atypical multinucleated cells in the lumen and degenerated germ cells in the adluminal compartment. BPP-10c led to an increase in the number of round spermatids and total support capacity of Sertoli cell in stages I, V, VII/VIII of the seminiferous epithelium cycle, without affecting BTB permeability

  16. Attenuation characteristics of monolayer graphene by Pi-and T-networks modeling of multilayer microstrip line

    Institute of Scientific and Technical Information of China (English)

    Pulkit Sharma; Sumit Pratap Singh; Kamlesh Patel

    2017-01-01

    The impedances of Pi-and T-networks are obtained from the measured S-parameters of the multilayer microstrip line by modeling as an attenuator.The changes in impedances have been analyzed for the properties of various superstrates at the microwave ranges.With graphene on glass and graphene on quartz loadings,the impedances have increased and shifted towards lower frequency more in Pi-network than T-network modeling.This shift has become more prominent at higher frequency for the graphene on glass than graphene on quartz.A little increase in attenuation is found for graphene on glass or quartz than bare glass and quartz.The present study can be extended to obtain attenuation characteristic of any thin film by simple experimental method in the microwave frequencies.

  17. Effect of water on self-assembled tubules in β-sitosterol + γ-oryzanol-based organogels

    Science.gov (United States)

    den Adel, Ruud; Heussen, Patricia C. M.; Bot, Arjen

    2010-10-01

    Mixtures of β-sitosterol and γ-oryzanol form a network in triglyceride oil that may serve as an alternative to the network of small crystallites of triglycerides occurring in regular oil structuring. The present x-ray diffraction study investigates the relation between the crystal forms of the individual compounds and the mixture in oil, water and emulsion. β-Sitosterol and γ-oryzanol form normal crystals in oil, in water, or in emulsions. The crystals are sensitive to the presence of water. The mixture of β-sitosterol + γ-oryzanol forms crystals in water and emulsions that can be traced back to the crystals of the pure compounds. Only in oil, a completely different structure emerges in the mixture of β-sitosterol + γ-oryzanol, which bears no relation to the structures that are formed by both individual compounds, and which can be identified as a self-assembled tubule (diameter 7.2±0.1 nm, wall thickness 0.8±0.2 nm).

  18. Effect of water on self-assembled tubules in {beta}-sitosterol + {gamma}-oryzanol-based organogels

    Energy Technology Data Exchange (ETDEWEB)

    Adel, Ruud den; Heussen, Patricia C M; Bot, Arjen, E-mail: ruud-den.adel@unilever.co [Unilever Research and Development Vlaardingen, Olivier van Noortlaan 120, NL-3133 AT Vlaardingen (Netherlands)

    2010-10-01

    Mixtures of {beta}-sitosterol and {gamma}-oryzanol form a network in triglyceride oil that may serve as an alternative to the network of small crystallites of triglycerides occurring in regular oil structuring. The present x-ray diffraction study investigates the relation between the crystal forms of the individual compounds and the mixture in oil, water and emulsion. {beta}-Sitosterol and {gamma}-oryzanol form normal crystals in oil, in water, or in emulsions. The crystals are sensitive to the presence of water. The mixture of {beta}-sitosterol + {gamma}-oryzanol forms crystals in water and emulsions that can be traced back to the crystals of the pure compounds. Only in oil, a completely different structure emerges in the mixture of {beta}-sitosterol + {gamma}-oryzanol, which bears no relation to the structures that are formed by both individual compounds, and which can be identified as a self-assembled tubule (diameter 7.2{+-}0.1 nm, wall thickness 0.8{+-}0.2 nm).

  19. Effect of water on self-assembled tubules in β-sitosterol + γ-oryzanol-based organogels

    International Nuclear Information System (INIS)

    Adel, Ruud den; Heussen, Patricia C M; Bot, Arjen

    2010-01-01

    Mixtures of β-sitosterol and γ-oryzanol form a network in triglyceride oil that may serve as an alternative to the network of small crystallites of triglycerides occurring in regular oil structuring. The present x-ray diffraction study investigates the relation between the crystal forms of the individual compounds and the mixture in oil, water and emulsion. β-Sitosterol and γ-oryzanol form normal crystals in oil, in water, or in emulsions. The crystals are sensitive to the presence of water. The mixture of β-sitosterol + γ-oryzanol forms crystals in water and emulsions that can be traced back to the crystals of the pure compounds. Only in oil, a completely different structure emerges in the mixture of β-sitosterol + γ-oryzanol, which bears no relation to the structures that are formed by both individual compounds, and which can be identified as a self-assembled tubule (diameter 7.2±0.1 nm, wall thickness 0.8±0.2 nm).

  20. Cellular localization of uranium in the renal proximal tubules during acute renal uranium toxicity.

    Science.gov (United States)

    Homma-Takeda, Shino; Kitahara, Keisuke; Suzuki, Kyoko; Blyth, Benjamin J; Suya, Noriyoshi; Konishi, Teruaki; Terada, Yasuko; Shimada, Yoshiya

    2015-12-01

    Renal toxicity is a hallmark of uranium exposure, with uranium accumulating specifically in the S3 segment of the proximal tubules causing tubular damage. As the distribution, concentration and dynamics of accumulated uranium at the cellular level is not well understood, here, we report on high-resolution quantitative in situ measurements by high-energy synchrotron radiation X-ray fluorescence analysis in renal sections from a rat model of uranium-induced acute renal toxicity. One day after subcutaneous administration of uranium acetate to male Wistar rats at a dose of 0.5 mg uranium kg(-1) body weight, uranium concentration in the S3 segment of the proximal tubules was 64.9 ± 18.2 µg g(-1) , sevenfold higher than the mean renal uranium concentration (9.7 ± 2.4 µg g(-1) ). Uranium distributed into the epithelium of the S3 segment of the proximal tubules and highly concentrated uranium (50-fold above mean renal concentration) in micro-regions was found near the nuclei. These uranium levels were maintained up to 8 days post-administration, despite more rapid reductions in mean renal concentration. Two weeks after uranium administration, damaged areas were filled with regenerating tubules and morphological signs of tissue recovery, but areas of high uranium concentration (100-fold above mean renal concentration) were still found in the epithelium of regenerating tubules. These data indicate that site-specific accumulation of uranium in micro-regions of the S3 segment of the proximal tubules and retention of uranium in concentrated areas during recovery are characteristics of uranium behavior in the kidney. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Tubulation of class II MHC compartments is microtubule dependent and involves multiple endolysosomal membrane proteins in primary dendritic cells.

    Science.gov (United States)

    Vyas, Jatin M; Kim, You-Me; Artavanis-Tsakonas, Katerina; Love, J Christopher; Van der Veen, Annemarthe G; Ploegh, Hidde L

    2007-06-01

    Immature dendritic cells (DCs) capture exogenous Ags in the periphery for eventual processing in endolysosomes. Upon maturation by TLR agonists, DCs deliver peptide-loaded class II MHC molecules from these compartments to the cell surface via long tubular structures (endolysosomal tubules). The nature and rules that govern the movement of these DC compartments are unknown. In this study, we demonstrate that the tubules contain multiple proteins including the class II MHC molecules and LAMP1, a lysosomal resident protein, as well as CD63 and CD82, members of the tetraspanin family. Endolysosomal tubules can be stained with acidotropic dyes, indicating that they are extensions of lysosomes. However, the proper trafficking of class II MHC molecules themselves is not necessary for endolysosomal tubule formation. DCs lacking MyD88 can also form endolysosomal tubules, demonstrating that MyD88-dependent TLR activation is not necessary for the formation of this compartment. Endolysosomal tubules in DCs exhibit dynamic and saltatory movement, including bidirectional travel. Measured velocities are consistent with motor-based movement along microtubules. Indeed, nocodazole causes the collapse of endolysosomal tubules. In addition to its association with microtubules, endolysosomal tubules follow the plus ends of microtubules as visualized in primary DCs expressing end binding protein 1 (EB1)-enhanced GFP.

  2. Piecewise-Constant-Model-Based Interior Tomography Applied to Dentin Tubules

    Directory of Open Access Journals (Sweden)

    Peng He

    2013-01-01

    Full Text Available Dentin is a hierarchically structured biomineralized composite material, and dentin’s tubules are difficult to study in situ. Nano-CT provides the requisite resolution, but the field of view typically contains only a few tubules. Using a plate-like specimen allows reconstruction of a volume containing specific tubules from a number of truncated projections typically collected over an angular range of about 140°, which is practically accessible. Classical computed tomography (CT theory cannot exactly reconstruct an object only from truncated projections, needless to say a limited angular range. Recently, interior tomography was developed to reconstruct a region-of-interest (ROI from truncated data in a theoretically exact fashion via the total variation (TV minimization under the condition that the ROI is piecewise constant. In this paper, we employ a TV minimization interior tomography algorithm to reconstruct interior microstructures in dentin from truncated projections over a limited angular range. Compared to the filtered backprojection (FBP reconstruction, our reconstruction method reduces noise and suppresses artifacts. Volume rendering confirms the merits of our method in terms of preserving the interior microstructure of the dentin specimen.

  3. Real-Time Performance of a Self-Powered Environmental IoT Sensor Network System.

    Science.gov (United States)

    Wu, Fan; Rüdiger, Christoph; Yuce, Mehmet Rasit

    2017-02-01

    Wireless sensor networks (WSNs) play an increasingly important role in monitoring applications in many areas. With the emergence of the Internet-of-Things (IoT), many more lowpower sensors will need to be deployed in various environments to collect and monitor data about environmental factors in real time. Providing power supply to these sensor nodes becomes a critical challenge for realizations of IoT applications as sensor nodes are normally battery-powered and have a limited lifetime. This paper proposes a wireless sensor network that is powered by solar energy harvesting. The sensor network monitors the environmental data with low-power sensor electronics and forms a network using multiple XBee wireless modules. A detailed performance analysis of the network system under solar energy harvesting has been presented. The sensor network system and the proposed energy-harvesting techniques are configured to achieve a continuous energy source for the sensor network. The proposed energy-harvesting system has been successfully designed to enable an energy solution in order to keep sensor nodes active and reliable for a whole day. The paper also outlines some of our experiences in real-time implementation of a sensor network system with energy harvesting.

  4. Real-Time Performance of a Self-Powered Environmental IoT Sensor Network System

    Directory of Open Access Journals (Sweden)

    Fan Wu

    2017-02-01

    Full Text Available Wireless sensor networks (WSNs play an increasingly important role in monitoring applications in many areas. With the emergence of the Internet-of-Things (IoT, many more lowpower sensors will need to be deployed in various environments to collect and monitor data about environmental factors in real time. Providing power supply to these sensor nodes becomes a critical challenge for realizations of IoT applications as sensor nodes are normally battery-powered and have a limited lifetime. This paper proposes a wireless sensor network that is powered by solar energy harvesting. The sensor network monitors the environmental data with low-power sensor electronics and forms a network using multiple XBee wireless modules. A detailed performance analysis of the network system under solar energy harvesting has been presented. The sensor network system and the proposed energy-harvesting techniques are configured to achieve a continuous energy source for the sensor network. The proposed energy-harvesting system has been successfully designed to enable an energy solution in order to keep sensor nodes active and reliable for a whole day. The paper also outlines some of our experiences in real-time implementation of a sensor network system with energy harvesting.

  5. Functionally induced changes in water transport in the proximal tubule segment of rat kidneys

    DEFF Research Database (Denmark)

    Faarup, Poul; von Holstein-Rathlou, Niels-Henrik; Nørgaard, Tove

    2011-01-01

    To eliminate freezing artifacts in the proximal tubule cells, two cryotechniques were applied to normal rat kidneys, ie, freeze substitution and special freeze drying. In addition, salt depletion and salt loading were applied to groups of rats to evaluate whether the segmental structure of the pr......To eliminate freezing artifacts in the proximal tubule cells, two cryotechniques were applied to normal rat kidneys, ie, freeze substitution and special freeze drying. In addition, salt depletion and salt loading were applied to groups of rats to evaluate whether the segmental structure...... segment, representing a structural background for the essential transport of water from the proximal tubules to the peritubular capillaries....

  6. Masonry structures built with fictile tubules: Experimental and numerical analyses

    Science.gov (United States)

    Tiberti, Simone; Scuro, Carmelo; Codispoti, Rosamaria; Olivito, Renato S.; Milani, Gabriele

    2017-11-01

    Masonry structures with fictile tubules were a distinctive building technique of the Mediterranean area. This technique dates back to Roman and early Christian times, used to build vaulted constructions and domes with various geometrical forms by virtue of their modular structure. In the present work, experimental tests were carried out to identify the mechanical properties of hollow clay fictile tubules and a possible reinforcing technique for existing buildings employing such elements. The experimental results were then validated by devising and analyzing numerical models with the FE software Abaqus, also aimed at investigating the structural behavior of an arch via linear and nonlinear static analyses.

  7. Chemically triggered ejection of membrane tubules controlled by intermonolayer friction.

    Science.gov (United States)

    Fournier, J-B; Khalifat, N; Puff, N; Angelova, M I

    2009-01-09

    We report a chemically driven membrane shape instability that triggers the ejection of a tubule growing exponentially toward a chemical source. The instability is initiated by a dilation of the exposed monolayer, which is coupled to the membrane spontaneous curvature and slowed down by intermonolayer friction. Our experiments are performed by local delivery of a basic pH solution to a giant vesicle. Quantitative fits of the data give an intermonolayer friction coefficient b approximately 2x10;{9} J s/m;{4}. The exponential growth of the tubule may be explained by a Marangoni stress yielding a pulling force proportional to its length.

  8. POINeT: protein interactome with sub-network analysis and hub prioritization

    Directory of Open Access Journals (Sweden)

    Lai Jin-Mei

    2009-04-01

    Full Text Available Abstract Background Protein-protein interactions (PPIs are critical to every aspect of biological processes. Expansion of all PPIs from a set of given queries often results in a complex PPI network lacking spatiotemporal consideration. Moreover, the reliability of available PPI resources, which consist of low- and high-throughput data, for network construction remains a significant challenge. Even though a number of software tools are available to facilitate PPI network analysis, an integrated tool is crucial to alleviate the burden on querying across multiple web servers and software tools. Results We have constructed an integrated web service, POINeT, to simplify the process of PPI searching, analysis, and visualization. POINeT merges PPI and tissue-specific expression data from multiple resources. The tissue-specific PPIs and the numbers of research papers supporting the PPIs can be filtered with user-adjustable threshold values and are dynamically updated in the viewer. The network constructed in POINeT can be readily analyzed with, for example, the built-in centrality calculation module and an integrated network viewer. Nodes in global networks can also be ranked and filtered using various network analysis formulas, i.e., centralities. To prioritize the sub-network, we developed a ranking filtered method (S3 to uncover potential novel mediators in the midbody network. Several examples are provided to illustrate the functionality of POINeT. The network constructed from four schizophrenia risk markers suggests that EXOC4 might be a novel marker for this disease. Finally, a liver-specific PPI network has been filtered with adult and fetal liver expression profiles. Conclusion The functionalities provided by POINeT are highly improved compared to previous version of POINT. POINeT enables the identification and ranking of potential novel genes involved in a sub-network. Combining with tissue-specific gene expression profiles, PPIs specific to

  9. Chloride secretagogues stimulate inositol phosphate formation in shark rectal gland tubules cultured in suspension

    International Nuclear Information System (INIS)

    Ecay, T.W.; Valentich, J.D.

    1991-01-01

    Neuroendocrine activation of transepithelial chloride secretion by shark rectal gland cells is associated with increases in cellular cAMP, cGMP, and free calcium concentrations. We report here on the effects of several chloride secretagogues on inositol phosphate formation in cultured rectal gland tubules. Vasoactive intestinal peptide (VIP), atriopeptin (AP), and ionomycin increase the total inositol phosphate levels of cultured tubules, as measured by ion exchange chromatography. Forskolin, a potent chloride secretagogue, has no effect on inositol phosphate formation. The uptake of 3 H-myo-inositol into phospholipids is very slow, preventing the detection of increased levels of inositol trisphosphate. However, significant increases in inositol monophosphate (IP1) and inositol biphosphate (IP2) were measured. The time course of VIP- and AP-stimulated IP1 and IP2 formation is similar to the effects of these agents on the short-circuit current responses of rectal gland monolayer cultures. In addition, aluminum fluoride, an artificial activator of guanine nucleotide-binding proteins, stimulates IP1 and IP2 formation. We conclude that rectal gland cells contain VIP and AP receptors coupled to the activation of phospholipase C. Coupling may be mediated by G-proteins. Receptor-stimulated increases in inositol phospholipid metabolism is one mechanism leading to increased intracellular free calcium concentrations, an important regulatory event in the activation of transepithelial chloride secretion by shark rectal gland epithelial cells

  10. How green are the TEN-T core network corridors?

    DEFF Research Database (Denmark)

    Panagakos, George; Psaraftis, Harilaos N.

    defining this concept, identified the characteristics that distinguish a green corridor from an otherwise efficient one. The main thesis of this paper is that the „core network corridors‟ of the new TEN-T guidelines exhibit all these qualities and the vision of a green corridor network in Europe is close...... to reality. To support this thesis, and in continuation of the work of SuperGreen, the paper examines the proposed new „guidelines‟ for the development of the TEN-T after presenting a brief history of transport network development in Europe....

  11. Tubulation of Class II MHC Compartments Is Microtubule Dependent and Involves Multiple Endolysosomal Membrane Proteins in Primary Dendritic Cells1

    Science.gov (United States)

    Vyas, Jatin M.; Kim, You-Me; Artavanis-Tsakonas, Katerina; Love, J. Christopher; Van der Veen, Annemarthe G.; Ploegh, Hidde L.

    2009-01-01

    Immature dendritic cells (DCs) capture exogenous Ags in the periphery for eventual processing in endolysosomes. Upon maturation by TLR agonists, DCs deliver peptide-loaded class II MHC molecules from these compartments to the cell surface via long tubular structures (endolysosomal tubules). The nature and rules that govern the movement of these DC compartments are unknown. In this study, we demonstrate that the tubules contain multiple proteins including the class II MHC molecules and LAMP1, a lysosomal resident protein, as well as CD63 and CD82, members of the tetraspanin family. Endolysosomal tubules can be stained with acidotropic dyes, indicating that they are extensions of lysosomes. However, the proper trafficking of class II MHC molecules themselves is not necessary for endolysosomal tubule formation. DCs lacking MyD88 can also form endolysosomal tubules, demonstrating that MyD88-dependent TLR activation is not necessary for the formation of this compartment. Endolysosomal tubules in DCs exhibit dynamic and saltatory movement, including bidirectional travel. Measured velocities are consistent with motor-based movement along microtubules. Indeed, nocodazole causes the collapse of endolysosomal tubules. In addition to its association with microtubules, endolysosomal tubules follow the plus ends of microtubules as visualized in primary DCs expressing end binding protein 1 (EB1)-enhanced GFP. PMID:17513769

  12. Role of calcium in the dopaminergic effect on the proximal convoluted tubule of rat kidney

    International Nuclear Information System (INIS)

    Chan, Y.L.; Chatsudthipong, V.; Su-Tsai, S.M.; von Riotte, A.

    1986-01-01

    Microperfusion studies have shown that dopamine inhibits fluid and bicarbonate absorption in the rate proximal tubule. These studies are designed to examine the cellular mechanism underlying the proximal cellular response to dopamine action. In the isolated proximal cells, dopamine, in the concentration of 10 -6 M or less, had no effect on cAMP production. However, dopamine could increase cytosolic calcium concentration (from 90 nM to 210 nM) as measured by fluorospectrometry with fura-2 as a calcium indicator. Ca-45 flux studies have shown that dopamine could increase initial influx but not the steady state uptake of Ca. Dopamine could also increase efflux of Ca. In situ microperfusion of proximal tubule and peritubular capillaries has demonstrated that Ca ionophore, A23187 (10 -6 M), could simulate the inhibitory effects of dopamine on fluid and biocarbonate absorption. There was no additive effect observed when both agents were added together in the capillary perfusate. Removal of calcium from the perfusate could partially blunt the effect of dopamine. These results suggest that intracellular calcium plays a crucial role in the dopaminergic regulation of proximal tubular transport

  13. A Multi-Hop Clustering Mechanism for Scalable IoT Networks.

    Science.gov (United States)

    Sung, Yoonyoung; Lee, Sookyoung; Lee, Meejeong

    2018-03-23

    It is expected that up to 26 billion Internet of Things (IoT) equipped with sensors and wireless communication capabilities will be connected to the Internet by 2020 for various purposes. With a large scale IoT network, having each node connected to the Internet with an individual connection may face serious scalability issues. The scalability problem of the IoT network may be alleviated by grouping the nodes of the IoT network into clusters and having a representative node in each cluster connect to the Internet on behalf of the other nodes in the cluster instead of having a per-node Internet connection and communication. In this paper, we propose a multi-hop clustering mechanism for IoT networks to minimize the number of required Internet connections. Specifically, the objective of proposed mechanism is to select the minimum number of coordinators, which take the role of a representative node for the cluster, i.e., having the Internet connection on behalf of the rest of the nodes in the cluster and to map a partition of the IoT nodes onto the selected set of coordinators to minimize the total distance between the nodes and their respective coordinator under a certain constraint in terms of maximum hop count between the IoT nodes and their respective coordinator. Since this problem can be mapped into a set cover problem which is known as NP-hard, we pursue a heuristic approach to solve the problem and analyze the complexity of the proposed solution. Through a set of experiments with varying parameters, the proposed scheme shows 63-87.3% reduction of the Internet connections depending on the number of the IoT nodes while that of the optimal solution is 65.6-89.9% in a small scale network. Moreover, it is shown that the performance characteristics of the proposed mechanism coincide with expected performance characteristics of the optimal solution in a large-scale network.

  14. Antioxidant Effects of Selenium on Seminiferous Tubules of Immature Mice Testis

    Directory of Open Access Journals (Sweden)

    Davoud Kushki

    2015-12-01

    Full Text Available Background: The freezing of immature testis tissue and then the transplant of it can be considered as a major step in fertility preservation for young boys with cancer, the survival of animal generation exposed to extinction and cloning animalistic desirable species. One of the most prevalent of damages in during the freezing-thawing process is oxidative stress. Objectives: The objective of this study was to investigate the antioxidant effects of selenium compound (Na2SeO3 on rate of seminiferous tubules injury in during of cryopreservation. Materials and Methods: In this experimental study, 8 BALB/c immature male mice (6 - 8 days old were randomly selected, and the testes removed surgically (n = 16. The testes divided into 2 groups: experimental group, control group (opposite testes. For each of the two experimental and control groups, two types of soluble (freezing solution and thawing solution were prepared. These solutions, which contain 2 mg/mL solution of Na2SeO3 and control solution, were prepared in the DMEM (Dulbecco’s modified eagle medium base medium. Of each group were 4 testes into fast freezing-thawing procedure and 4 testes were into slow freezing-thawing procedure. Then this testis for analyzing injury, after preparatory process, was stained with hematoxylin-eosin. Results: At the slow freezing-thawing procedure, seminiferous tubules injury significantly reduced in experimental group compared to control group. At the fast freezing-thawing procedure, seminiferous tubules injury significantly reduced in experimental group compared with of control group. Conclusions: It seems that Se due to its antioxidant properties, the harmful effects of freezing-thawing process reduces and protects seminiferous tubules from oxidative injury.

  15. In Vitro Evaluation of Dentin Tubule Occlusion for Novel Calcium Lactate Phosphate (CLP Paste

    Directory of Open Access Journals (Sweden)

    Jen-Chang Yang

    2017-02-01

    Full Text Available Introduction: The objective of this in vitro study is to evaluate the effective and long-term occlusion of dentinal tubules using a novel calcium lactate phosphate (CLP based desensitizing agent. Methods: Dentin disks (n = 9 were pre-etched using 1 M lactic acid for 30 s and individually treated with Colgate® Pro-Relief™ paste, CLP paste, and double distilled water (ddH2O by a rubber-cupped handpiece. Dentin disks were analyzed under optical micrographs for pre-treatment, directly after treatment, and 14 days post-treatment. One-way ANOVA and post-hoc Tukey’s test were used to determine whether there were any statistically significant differences in dentinal tubule diameter. Results: A significant decrease occurred in the mean tubule diameter for dentin disks treated with CLP paste. A decrease was observed from 3.52 ± 0.83 µm to 2.62 ± 0.42 µm right after treatment, further decreasing to 1.71 ± 0.45 µm after immersion in artificial saliva for 14 days (p < 0.05. Conclusions: The results suggest that the CLP based desensitizing paste has remineralization properties and provides instant and lasting effectiveness in dentinal tubule occlusion.

  16. Towards A New Opportunistic IoT Network Architecture for Wildlife Monitoring System

    NARCIS (Netherlands)

    Ayele, Eyuel Debebe; Meratnia, Nirvana; Havinga, Paul J.M.

    In this paper we introduce an opportunistic dual radio IoT network architecture for wildlife monitoring systems (WMS). Since data processing consumes less energy than transmitting the raw data, the proposed architecture leverages opportunistic mobile networks in a fixed LPWAN IoT network

  17. Locally formed dopamine inhibits Na+-K+-ATPase activity in rat renal cortical tubule cells

    International Nuclear Information System (INIS)

    Seri, I.; Kone, B.C.; Gullans, S.R.; Aperia, A.; Brenner, B.M.; Ballermann, B.J.

    1988-01-01

    Dopamine, generated locally from L-dopa, inhibits Na + -K + -ATPase in permeabilized rat proximal tubules under maximum transport rate conditions for sodium. To determine whether locally formed dopamine inhibits Na + -K + -ATPase activity in intact cortical tubule cells we studied the effect of L-dopa on ouabain-sensitive oxygen consumption rate (Qo 2 ) and 86 Rb uptake in renal cortical tubule cell suspensions. L-Dopa did not affect ouabain-insensitive Qo 2 or mitochondrial respiration. However, L-dopa inhibited ouabain-sensitive Qo 2 in a concentration-dependent manner, with half-maximal inhibition (K 0.5 ) of 5 x 10 -7 M and a maximal inhibition of 14.1 ± 1.5% at 10 -4 M. L-Dopa also blunted the nystatin-stimulated Qo 2 in a concentration-dependent manner, indicating the L-dopa directly inhibits Na + -K + -ATPase activity and not sodium entry. Ouabain-sensitive 86 Rb uptake was also inhibited by L-dopa. Carbidopa, an inhibitor of the conversion of L-dopa to dopamine, eliminated the effect of L-dopa on ouabain-sensitive Qo 2 and 86 Rb uptake, indicating that dopamine rather than L-dopa was the active agent. The finding that the L-dopa concentration-response curve was shifted to the left by one order of magnitude in the presence of nystatin suggests that the inhibitory effect is enhanced when the intracellular sodium concentration is increased. By studying the effect of L-dopa on ouabain-sensitive Qo 2 at increasing extracellular sodium concentrations in the presence of nystatin, the authors demonstrated that the inhibitory effect of locally formed dopamine on the Na + -K + -ATPase is indeed dependent on the sodium available for the enzyme and occurs in an uncompetitive manner

  18. Dentinal tubule occluding capability of nano-hydroxyapatite; The in-vitro evaluation.

    Science.gov (United States)

    Baglar, Serdar; Erdem, Umit; Dogan, Mustafa; Turkoz, Mustafa

    2018-04-29

    In this in-vitro study, the effectiveness of experimental pure nano-hydroxyapatite (nHAP) and 1%, 2%, and 3% F¯ doped nano-HAp on dentine tubule occlusion was investigated. And also, the cytotoxicity of materials used in the experiment was evaluated. Nano-HAp types were synthesized by the precipitation method. Forty dentin specimens were randomly divided into five groups of; 1-no treatment (control), 2-specimens treated with 10% pure nano-HAp and 3, 4, 5 specimens treated with 1%, 2%, and 3% F - doped 10% nano-HAp, respectively. To evaluate the effectiveness of the materials used; pH, FTIR, and scanning electron microscopy evaluations were performed before and after degredation in simulated body fluid. To determine cytotoxicity of the materials, MTT assay was performed. Statistical evaluations were performed with F and t tests. All of the nano-HAp materials used in this study built up an effective covering layer on the dentin surfaces even with plugs in tubules. It was found that this layer had also a resistance to degradation. None of the evaluated nano-HAp types were have toxicity. Fluoride doping showed a positive effect on physical and chemical stability until a critical value of 1% F - . The all evaluated nano-HAp types may be effectively used in dentin hypersensitivity treatment. The formed nano-HAp layers were seem to resistant to hydrolic deletion. The pure and 1% F - doped nano-HAp showed the highest biocompatibility thus it was assessed that pure and 1% F - doped materials may be used as an active ingredient in dentin hypersensitivity agents. © 2018 Wiley Periodicals, Inc.

  19. Cadmium transport by the gut and Malpighian tubules of Chironomus riparius

    International Nuclear Information System (INIS)

    Leonard, Erin M.; Pierce, Laura M.; Gillis, Patricia L.; Wood, Chris M.; O'Donnell, Michael J.

    2009-01-01

    Many aquatic insects are very insensitive to cadmium in short-term laboratory studies. LC50 values for larvae of the midge Chironomus riparius are over 25,000 times the Criterion Maximum Concentration in the United States Environmental Protection Agency (U.S. EPA (2000)) species sensitivity distribution (SSD). Excretion or sequestration of cadmium may contribute to insensitivity and we have therefore examined cadmium transport by isolated guts and renal tissues of C. riparius larvae. Regional differences of Cd transport along the gut were identified using a Cd 2+ -selective microelectrode in conjunction with the Scanning Ion-Selective Electrode Technique (SIET). Cd is transported into the anterior midgut (AMG) cells from the lumen and out of the cells into the hemolymph. The transport of Cd from the gut lumen to the hemolymph exposes other tissues such as the nervous system and muscles to Cd. The gut segments which remove Cd from the hemolymph at the highest rate are the posterior midgut (PMG) and the ileum. In addition, assays using an isolated Malpighian (renal) tubule preparation have shown that the Malpighian tubules (MT) both sequester and secrete Cd. For larvae bathed in 10 μmol l -1 Cd, the tubules can secrete the entire hemolymph burden of Cd in ∼15 h.

  20. The Lowe syndrome protein OCRL1 is required for endocytosis in the zebrafish pronephric tubule.

    Directory of Open Access Journals (Sweden)

    Francesca Oltrabella

    2015-04-01

    Full Text Available Lowe syndrome and Dent-2 disease are caused by mutation of the inositol 5-phosphatase OCRL1. Despite our increased understanding of the cellular functions of OCRL1, the underlying basis for the renal tubulopathy seen in both human disorders, of which a hallmark is low molecular weight proteinuria, is currently unknown. Here, we show that deficiency in OCRL1 causes a defect in endocytosis in the zebrafish pronephric tubule, a model for the mammalian renal tubule. This coincides with a reduction in levels of the scavenger receptor megalin and its accumulation in endocytic compartments, consistent with reduced recycling within the endocytic pathway. We also observe reduced numbers of early endocytic compartments and enlarged vacuolar endosomes in the sub-apical region of pronephric cells. Cell polarity within the pronephric tubule is unaffected in mutant embryos. The OCRL1-deficient embryos exhibit a mild ciliogenesis defect, but this cannot account for the observed impairment of endocytosis. Catalytic activity of OCRL1 is required for renal tubular endocytosis and the endocytic defect can be rescued by suppression of PIP5K. These results indicate for the first time that OCRL1 is required for endocytic trafficking in vivo, and strongly support the hypothesis that endocytic defects are responsible for the renal tubulopathy in Lowe syndrome and Dent-2 disease. Moreover, our results reveal PIP5K as a potential therapeutic target for Lowe syndrome and Dent-2 disease.

  1. Organic anion and cation SLC22 "drug" transporter (Oat1, Oat3, and Oct1 regulation during development and maturation of the kidney proximal tubule.

    Directory of Open Access Journals (Sweden)

    Thomas F Gallegos

    Full Text Available Proper physiological function in the pre- and post-natal proximal tubule of the kidney depends upon the acquisition of selective permeability, apical-basolateral epithelial polarity and the expression of key transporters, including those involved in metabolite, toxin and drug handling. Particularly important are the SLC22 family of transporters, including the organic anion transporters Oat1 (originally identified as NKT and Oat3 as well as the organic cation transporter Oct1. In ex vivo cultures of metanephric mesenchyme (MM; the embryonic progenitor tissue of the nephron Oat function was evident before completion of nephron segmentation and corresponded with the maturation of tight junctions as measured biochemically by detergent extractability of the tight junction protein, ZO-1. Examination of available time series microarray data sets in the context of development and differentiation of the proximal tubule (derived from both in vivo and in vitro/ex vivo developing nephrons allowed for correlation of gene expression data to biochemically and functionally defined states of development. This bioinformatic analysis yielded a network of genes with connectivity biased toward Hnf4α (but including Hnf1α, hyaluronic acid-CD44, and notch pathways. Intriguingly, the Oat1 and Oat3 genes were found to have strong temporal co-expression with Hnf4α in the cultured MM supporting the notion of some connection between the transporters and this transcription factor. Taken together with the ChIP-qPCR finding that Hnf4α occupies Oat1, Oat3, and Oct1 proximal promoters in the in vivo differentiating rat kidney, the data suggest a network of genes with Hnf4α at its center plays a role in regulating the terminal differentiation and capacity for drug and toxin handling by the nascent proximal tubule of the kidney.

  2. Architecture of the rat nephron-arterial network

    DEFF Research Database (Denmark)

    Marsh, Donald J; Postnov, Dmitry D; Rowland, Douglas

    2017-01-01

    Among solid organs the kidney's vascular network stands out because each nephron has 2 distinct capillary structures in series, and because tubuloglomerular feedback (TGF), one of the mechanisms responsible for blood flow autoregulation, is specific to renal tubules. TGF and the myogenic mechanis...

  3. Morphometry of testis and seminiferous tubules of the adult crab-eating fox (Cerdocyon thous, Linnaeus, 1766

    Directory of Open Access Journals (Sweden)

    Bianca Cabral Caldeira

    2010-10-01

    Full Text Available Body and testicular biometric parameters are very important for establishing reproductive patterns and, consequently, the development of protocols for assisted reproduction in different species. A direct correlation between the testis weight and the sperm population was observed in other studied species, because the testis size primarily reflects the total volume of the seminiferous tubule, its main component. The objective of this study was to determine the testicular volume parameters and correlate data from morphometry of testis and seminiferous tubules with body mass in six adult crab-eating foxes. The mean body weight of the crab-eating foxes in this study was 6.53 kg, with approximately 0.068% allocated to the testicular mass and 0.042% specifically to seminiferous tubules, which represented 87.5% of the testicular parenchyma. The albuginea comprised 12.5% of the testicular mass. The mean diameter of seminiferous tubules was 236 µm, and the mean thickness of the seminiferous epithelium was 62.9 µm. Values of tubular parameters indicate a sperm productivity close to those observed in previously studied carnivores.

  4. Subcellular distribution of folate and folate binding protein in renal proximal tubules

    International Nuclear Information System (INIS)

    Sharkey, C.; Hjelle, J.T.; Selhub, J.

    1986-01-01

    High affinity folate binding protein (FBP) found in brush border membranes derived from renal cortices is thought to be involved in the renal conservation of folate. To examine the mechanisms of folate recovery, the subcellular distribution of FBP and 3 H-folate in rabbit renal proximal tubules (PT) was examined using analytical cell fractionation techniques. Tubules contain 3.41 +/- 0.32 picomoles FBP/mg protein (X +/- S.D.; n = 5). Postnuclear supernates (PNS) of PT were layered atop Percoll-sucrose gradients, centrifuged, fractions collected and assayed for various marker enzymes and FBP. Pooled fractions from such gradients were subsequently treated with digitonin and centrifuged in a stoichiometric manner with the activity of the microvillar enzyme, alanylaminopeptidase (AAP); excess FBP distributed with more buoyant particles. Infusion of 3 H-folate into rabbit kidneys followed by tubule isolation and fractionation revealed a time dependent shift in distribution of radiolabel from the AAP-rich gradient fractions to a region containing more buoyant particles; radiolevel was not associated with lysosomal markers. EM-radioautography revealed grains over intracellular vesicles. These results are consistent with the hypothesis that folate is recovered by a process involving receptor-mediated endocytosis or transcytosis

  5. Studies on the origin and structure of tubules made by the movement protein of Cowpea mosaic virus

    NARCIS (Netherlands)

    Pouwels, J.; Velden, van der T.; Willemse, J.; Borst, J.W.; Lent, van J.W.M.; Bisseling, T.; Wellink, J.E.

    2004-01-01

    Cowpea mosaic virus (CPMV) moves from cell to cell by transporting virus particles via tubules formed through plasmodesmata by the movement protein (MP). On the surface of protoplasts, a fusion between the MP and the green fluorescent protein forms similar tubules and peripheral punctate spots. Here

  6. A gene regulatory network armature for T-lymphocyte specification

    Energy Technology Data Exchange (ETDEWEB)

    Fung, Elizabeth-sharon [Los Alamos National Laboratory

    2008-01-01

    Choice of a T-lymphoid fate by hematopoietic progenitor cells depends on sustained Notch-Delta signaling combined with tightly-regulated activities of multiple transcription factors. To dissect the regulatory network connections that mediate this process, we have used high-resolution analysis of regulatory gene expression trajectories from the beginning to the end of specification; tests of the short-term Notchdependence of these gene expression changes; and perturbation analyses of the effects of overexpression of two essential transcription factors, namely PU.l and GATA-3. Quantitative expression measurements of >50 transcription factor and marker genes have been used to derive the principal components of regulatory change through which T-cell precursors progress from primitive multipotency to T-lineage commitment. Distinct parts of the path reveal separate contributions of Notch signaling, GATA-3 activity, and downregulation of PU.l. Using BioTapestry, the results have been assembled into a draft gene regulatory network for the specification of T-cell precursors and the choice of T as opposed to myeloid dendritic or mast-cell fates. This network also accommodates effects of E proteins and mutual repression circuits of Gfil against Egr-2 and of TCF-l against PU.l as proposed elsewhere, but requires additional functions that remain unidentified. Distinctive features of this network structure include the intense dose-dependence of GATA-3 effects; the gene-specific modulation of PU.l activity based on Notch activity; the lack of direct opposition between PU.l and GATA-3; and the need for a distinct, late-acting repressive function or functions to extinguish stem and progenitor-derived regulatory gene expression.

  7. Passive permeability of salicylic acid in renal proximal S2 and S3 tubules

    International Nuclear Information System (INIS)

    Chatton, J.Y.; Roch-Ramel, F.

    1991-01-01

    The role of nonionic diffusion in the transport of salicylic acid across rabbit proximal S2 and S3 segments was investigated using the in vitro isolated perfused tubule technique. The [ 14 C] salicylic acid apparent reabsorptive permeability (P'I-b, 10(-5) cm/s) was measured at 19 degrees C with luminal solutions kept at different pH and bath maintained at pH 7.4. In S2 tubules, P'I-b was 25.0 +/- 3.5 when luminal pH was 6.0; P'I-b decreased to 8.1 +/- 1.4 and to 4.4 +/- 1.2 at a luminal pH of 6.5 and 7.0, respectively. In S3 tubules, P'I-b was 17.6 +/- 2.4, 5.3 +/- 1.1 and 3.4 +/- 1.1 at a luminal pH of 6.0, 6.5 and 7.0, respectively. There was a close correlation between P'I-b and the calculated proportion of nonionized salicylic acid present at each pH, indicating that only the nonionized molecule could diffuse in our conditions. We calculated the apparent permeability of nonionic salicylic acid and found 0.248 +/- 0.032 cm/s for S2 and 0.176 +/- 0.022 cm/s for S3 tubules. These calculated permeabilities were independent of pH

  8. Spatiotemporal Stochastic Modeling of IoT Enabled Cellular Networks: Scalability and Stability Analysis

    KAUST Repository

    Gharbieh, Mohammad; Elsawy, Hesham; Bader, Ahmed; Alouini, Mohamed-Slim

    2017-01-01

    The Internet of Things (IoT) is large-scale by nature, which is manifested by the massive number of connected devices as well as their vast spatial existence. Cellular networks, which provide ubiquitous, reliable, and efficient wireless access, will play fundamental rule in delivering the first-mile access for the data tsunami to be generated by the IoT. However, cellular networks may have scalability problems to provide uplink connectivity to massive numbers of connected things. To characterize the scalability of cellular uplink in the context of IoT networks, this paper develops a traffic-aware spatiotemporal mathematical model for IoT devices supported by cellular uplink connectivity. The developed model is based on stochastic geometry and queueing theory to account for the traffic requirement per IoT device, the different transmission strategies, and the mutual interference between the IoT devices. To this end, the developed model is utilized to characterize the extent to which cellular networks can accommodate IoT traffic as well as to assess and compare three different transmission strategies that incorporate a combination of transmission persistency, backoff, and power-ramping. The analysis and the results clearly illustrate the scalability problem imposed by IoT on cellular network and offer insights into effective scenarios for each transmission strategy.

  9. Spatiotemporal Stochastic Modeling of IoT Enabled Cellular Networks: Scalability and Stability Analysis

    KAUST Repository

    Gharbieh, Mohammad

    2017-05-02

    The Internet of Things (IoT) is large-scale by nature, which is manifested by the massive number of connected devices as well as their vast spatial existence. Cellular networks, which provide ubiquitous, reliable, and efficient wireless access, will play fundamental rule in delivering the first-mile access for the data tsunami to be generated by the IoT. However, cellular networks may have scalability problems to provide uplink connectivity to massive numbers of connected things. To characterize the scalability of cellular uplink in the context of IoT networks, this paper develops a traffic-aware spatiotemporal mathematical model for IoT devices supported by cellular uplink connectivity. The developed model is based on stochastic geometry and queueing theory to account for the traffic requirement per IoT device, the different transmission strategies, and the mutual interference between the IoT devices. To this end, the developed model is utilized to characterize the extent to which cellular networks can accommodate IoT traffic as well as to assess and compare three different transmission strategies that incorporate a combination of transmission persistency, backoff, and power-ramping. The analysis and the results clearly illustrate the scalability problem imposed by IoT on cellular network and offer insights into effective scenarios for each transmission strategy.

  10. Optimizing mission critical data dissemination in massive IoT networks

    KAUST Repository

    Farooq, Muhammad Junaid

    2017-06-29

    Mission critical data dissemination in massive Internet of things (IoT) networks imposes constraints on the message transfer delay between devices. Due to low power and communication range of IoT devices, data is foreseen to be relayed over multiple device-to-device (D2D) links before reaching the destination. The coexistence of a massive number of IoT devices poses a challenge in maximizing the successful transmission capacity of the overall network alongside reducing the multi-hop transmission delay in order to support mission critical applications. There is a delicate interplay between the carrier sensing threshold of the contention based medium access protocol and the choice of packet forwarding strategy selected at each hop by the devices. The fundamental problem in optimizing the performance of such networks is to balance the tradeoff between conflicting performance objectives such as the spatial frequency reuse, transmission quality, and packet progress towards the destination. In this paper, we use a stochastic geometry approach to quantify the performance of multi-hop massive IoT networks in terms of the spatial frequency reuse and the transmission quality under different packet forwarding schemes. We also develop a comprehensive performance metric that can be used to optimize the system to achieve the best performance. The results can be used to select the best forwarding scheme and tune the carrier sensing threshold to optimize the performance of the network according to the delay constraints and transmission quality requirements.

  11. The development of enamel tubules during the formation of enamel in the marsupial Monodelphis domestica.

    OpenAIRE

    Sasagawa, I; Ferguson, M W

    1991-01-01

    In Monodelphis domestica, although both processes from odontoblasts and projections from ameloblasts were found in developing enamel, the majority of the contents of enamel tubules were probably processes that originated from odontoblasts. Processes from odontoblasts penetrating into enamel touched part of the ameloblasts in the stage of enamel formation. No specialised cell junctions were seen at the adherence between the two. There were no enamel tubules in the aprismatic and pseudoprismati...

  12. Role of diacylglycerol in adrenergic-stimulated sup 86 Rb uptake by proximal tubules

    Energy Technology Data Exchange (ETDEWEB)

    Baines, A.D.; Drangova, R.; Ho, P. (Univ. of Toronto, Ontario (Canada))

    1990-05-01

    We used rat proximal tubule fragments purified by Percoll centrifugation to examine the role of diacylglycerol (DAG) in noradrenergic-stimulated Na+ reabsorption. Tubular DAG concentration and ouabain-inhibitable 86Rb uptake increased within 30 s after adding norepinephrine (NE) and remained elevated for at least 5 min. NE (1 microM) increased DAG content 17% and ouabain-inhibitable 86Rb uptake 23%. Cirazoline-stimulated 86Rb uptake was not inhibited by BaCl, quinidine, or bumetanide (1-10 microM) or by the omission of HCO3- or Cl- from the medium, but it was completely inhibited by ouabain and furosemide. Oleoyl-acetyl glycerol, L-alpha-1,2-dioctanoylglycerol, and L-alpha-1,2-dioleoylglycerol (DOG) increased total 86Rb uptake 8-11%. 12-O-tetradecanoylphorbol-13-acetate (TPA) (5 nM) increased uptake by only 4%. Staurosporine at 5 nM inhibited DOG stimulation completely, whereas 50 nM staurosporine was required to inhibit NE stimulation completely. Sphingosine inhibited DOG stimulation by 66% but did not inhibit NE stimulation. Amiloride (1 mM) completely blocked DOG stimulation. Monensin increased 86Rb uptake 31% and completely blocked the DOG effect but reduced the NE effect by only 26% (P = 0.08). In tubules from salt-loaded rats, NE did not increase DAG concentration, but NE-stimulated 86Rb uptake was reduced by only 23% (P = 0.15). Thus DAG released by NE may stimulate Na+ entry through Na(+)-H+ exchange. NE predominantly stimulates Na(+)-K(+)-adenosinetriphosphatase (ATPase) by activating a protein kinase that is insensitive to DAG and TPA and is inhibited by staurosporine but not by sphingosine. NE may also stimulate K+ efflux through a BaCl-insensitive K+ channel that is inhibited by millimolar furosemide.

  13. Fluid transport and ion fluxes in mammalian kidney proximal tubule: a model analysis of isotonic transport

    DEFF Research Database (Denmark)

    Larsen, E.H.; Møbjerg, N.; Sørensen, Jens Nørkær

    2006-01-01

    transport similar to rat proximal tubule. Na+ recirculation is required for truly isotonic transport. The tonicity of the absorbate and the recirculation flux depend critically on ion permeabilities of interspace basement membrane. Conclusion: Our model based on solute-solvent coupling in lateral space......Aim: By mathematical modelling, we analyse conditions for near-isotonic and isotonic transport by mammalian kidney proximal tubule. Methods: The model comprises compliant lateral intercellular space (lis) and cells, and infinitely large luminal and peritubular compartments with diffusible species......: Na+, K+, Cl and an intracellular non-diffusible anion. Unknown model variables are solute concentrations, electrical potentials, volumes and hydrostatic pressures in cell and lis, and transepithelial potential. We used data mainly from rat proximal tubule to model epithelial cells and interspace...

  14. Transport of water in proximal kidney tubules from whole tubules to single channels: length and section of the selectivity filter of aquaporin-1.

    Science.gov (United States)

    Whittembury, G; González, E; Hernández, C S; Gutiérrez, A M; Echevarría, M

    1997-06-27

    Proximal straight tubule (PST) were dissected from rabbit kidneys, held with crimping pipettes in a chamber bathed in a buffered mannitol isosmotic solution (MBS, 295 mOsm/kg). Tubule cell volume changes with time (dV/Adt) after steps in MBS osmolality (delta Cs) were monitored on line with an inverted microscope, a TV camera and an image processor. Reflection coefficients sigma and osmotic permeability coefficients, Pos, for several solutes were measured using two methods. Method 1: sigma was calculated from the delta Csiso of impermeant and permeant solutes at which (dV/Adt)t-->0 = 0 (i.e., by a null point method). It is denoted as sigma 1. sigma 1 = 1.00 for mannitol (M), raffinose (R), sucrose (S), glycerol (G), acetamide (A) and urea (U). With formamide (F), sigma 1, Formamide = 0.62 +/- 0.05. These findings confirm our previous value of dp = 4.5 A for the diameter of the selectivity filter of the basolateral PST cell membrane water channel AQP1. Method 2: PST were exposed for 20 s to MBS made hyperosmotic by addition of a delta Cs of 35 mOsm/kg of R, S, M, G, A and U. Cells shrunk within 500 ms of t = 0 to their osmometric volume and remained shrunk for the 20 s of the osmotic challenge. Pos was measured from the shrinking curves. P(os) = 3000 +/- 25 microns/s with R, S, M, G, A and U. Method 2 also allowed to calculate sigma, denoted as sigma 2. sigma 2 = 1.00 for R, S, M, G, A and U. By contrast, the shrinking curve produced by a delta Cs of 35 mOsm/kg F was 1/5th to 1/6th slower and smaller (i.e., subosmometric) than that produced by a delta Cs of 35 mOsm/kg R, S, M, G, A and U. Furthermore, with F cells did not remain shrunk but recovered their original volume within 3 s. P(os) (measured with F) is denoted as P(os)*, P(os)* = 480 +/- 30 microns/s. sigma 2, Formamide = 0.16 +/- 0.01. Use of sigma 1, sigma 2 and P(os)* values in Hill's equations for the bimodal theory of osmosis leads to n = 2-9. Where n is the number of water molecules single filling

  15. Performance Analysis of Dual-Polarized Massive MIMO System with Human-Care IoT Devices for Cellular Networks

    Directory of Open Access Journals (Sweden)

    Jun-Ki Hong

    2018-01-01

    Full Text Available The performance analysis of the dual-polarized massive multiple-input multiple-output (MIMO system with Internet of things (IoT devices is studied when outdoor human-care IoT devices are connected to a cellular network via a dual-polarized massive MIMO system. The research background of the performance analysis of dual-polarized massive MIMO system with IoT devices is that recently the data usage of outdoor human-care IoT devices has increased. Therefore, the outdoor human-care IoT devices are necessary to connect with 5G cellular networks which can expect 1000 times higher performance compared with 4G cellular networks. Moreover, in order to guarantee the safety of the patient for emergency cases, a human-care Iot device must be connected to cellular networks which offer more stable communication for outdoors compared to short-range communication technologies such as Wi-Fi, Zigbee, and Bluetooth. To analyze the performance of the dual-polarized massive MIMO system for human-care IoT devices, a dual-polarized MIMO spatial channel model (SCM is proposed which considers depolarization effect between the dual-polarized transmit-antennas and the receive-antennas. The simulation results show that the performance of the dual-polarized massive MIMO system is improved about 16% to 92% for 20 to 150 IoT devices compared to conventional single-polarized massive MIMO system for identical size of the transmit array.

  16. Structural and functional alterations in Malpighian tubules as biomarkers of environmental pollution: synopsis and prospective.

    Science.gov (United States)

    Giglio, Anita; Brandmayr, Pietro

    2017-08-01

    Although a number of biomarkers of pollutant exposure have been identified in invertebrate species, little is known about the effect on Malpighian tubules playing an essential role in excretion and osmoregulation. Analyses of structural and functional alterations on this organ can be useful to predict the effects at the organism and population level in monitoring studies of environmental pollution. The aim of the present review is to provide a synthesis of existing knowledge on cellular damages induced by xenobiotics in Malpighian tubules both under laboratory and field conditions. We compared studies of exposure to pesticides and heavy metals as mainly environmental contaminants from anthropogenic activities. This report provided evidence that the exposure to xenobiotics has an effect on this organ and reinforces the need for further research integrating molecular biomarkers with analysis on Malpighian tubules. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Early effects of aldosterone on Na-K pump in rat cortical collecting tubules

    International Nuclear Information System (INIS)

    Fujii, Y.; Takemoto, F.; Katz, A.I.

    1990-01-01

    Sustained exposure to aldosterone (Aldo) increases the abundance and activity of the Na-K pump in cortical collecting tubules (CCT). However, the onset and mechanism of the early interaction of Aldo with the CCT pump, especially in adrenal-intact animals, are unclear. We evaluated the short-term effects of the hormone on Na-K-adenosinetriphosphatase (ATPase) activity and on ouabain-sensitive 86Rb uptake, a measure of the transporting rate of the pump, in microdissected CCT from adrenal-intact rats. Incubation with Aldo (10(-8) M, 2 h) had no effect on Na-K-ATPase activity (Vmax), whereas it produced at least a twofold increase in 86Rb uptake. This effect was generated by physiological concentrations of the hormone (threshold 10(-10) M; apparent K1/2 approximately 10(-9) M), after a short lag of less than or equal to 30 min. Incubation with Aldo in the presence of amiloride or nystatin or in a Na-free medium (choline chloride) did not prevent the enhanced 86Rb uptake seen after Aldo alone; possible interpretations of these observations are discussed. We conclude that Aldo produces a rapid stimulation of pump function in CCT that precedes its induction of new pump synthesis; the physiological significance of this effect is suggested by its occurrence in tubules from adrenal-intact animals within the time frame and concentration range of the hormone's effects on electrolyte transport

  18. Acid-base transport by the renal proximal tubule.

    Science.gov (United States)

    Skelton, Lara A; Boron, Walter F; Zhou, Yuehan

    2010-01-01

    Each day, the kidneys filter 180 L of blood plasma, equating to some 4,300 mmol of the major blood buffer, bicarbonate (HCO3-). The glomerular filtrate enters the lumen of the proximal tubule (PT), and the majority of filtered HCO3- is reclaimed along the early (S1) and convoluted (S2) portions of the PT in a manner coupled to the secretion of H+ into the lumen. The PT also uses the secreted H+ to titrate non-HCO3- buffers in the lumen, in the process creating "new HCO3-" for transport into the blood. Thus, the PT - along with more distal renal segments - is largely responsible for regulating plasma [HCO3-]. In this review we first focus on the milestone discoveries over the past 50+ years that define the mechanism and regulation of acid-base transport by the proximal tubule. Further on in the review, we will summarize research still in progress from our laboratory, work that addresses the problem of how the PT is able to finely adapt to acid-base disturbances by rapidly sensing changes in basolateral levels of HCO3- and CO2 (but not pH), and thereby to exert tight control over the acid-base composition of the blood plasma.

  19. Reversible effects of acute hypertension on proximal tubule sodium transporters

    DEFF Research Database (Denmark)

    Zhang, Y; Magyar, C E; Norian, J M

    1998-01-01

    Acute hypertension provokes a rapid decrease in proximal tubule sodium reabsorption with a decrease in basolateral membrane sodium-potassium-ATPase activity and an increase in the density of membranes containing apical membrane sodium/hydrogen exchangers (NHE3) [Y. Zhang, A. K. Mircheff, C. B....... Renal cortex lysate was fractionated on sorbitol gradients. Basolateral membrane sodium-potassium-ATPase activity (but not subunit immunoreactivity) decreased one-third to one-half after BP was elevated and recovered after BP was normalized. After BP was elevated, 55% of the apical NHE3 immunoreactivity......, smaller fractions of sodium-phosphate cotransporter immunoreactivity, and apical alkaline phosphatase and dipeptidyl-peptidase redistributed to membranes of higher density enriched in markers of the intermicrovillar cleft (megalin) and endosomes (Rab 4 and Rab 5), whereas density distributions...

  20. X radiation effect in the proximal contorted renal tubules of mice

    International Nuclear Information System (INIS)

    Pacheco, I.P.

    1977-01-01

    Exposing C 57B1, 100 days old, mice to X-ray radiation in doses of 150, 300 and 400 R was observed in the proximal contorted renal tubules. An early appearance of unspecific alterations which are peculiar to ageing [pt

  1. Effects of bioactive glass with and without mesoporous structures on desensitization in dentinal tubule occlusion

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Wen-Cheng [Advanced Medical Devices and Composites Laboratory, Department of Fiber and Composite Materials, College of Engineering, Feng Chia University, Taichung 40724, Taiwan (China); Kung, Jung-Chang [Department of Family Dentistry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Chen, Cheng-Hwei [School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Hsiao, Yu-Cheng [Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Shih, Chi-Jen, E-mail: cjshih@kmu.edu.tw [Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chien, Chi-Sheng, E-mail: jannie.gissing@msa.hinet.net [Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan (China); Department of Orthopaedics, Chi Mei Foundation Hospital, Tainan, Taiwan (China); Department of Electrical Engineering, Southern Taiwan University of Science and Technology, Tainan, Taiwan (China)

    2013-10-15

    Bioactive glass (BG) is a potential material for treating dentin hypersensitivity due to its high ability of dissolution. In this study, conventional BG and BG with well-ordered mesopore structures (MBG) were applied for dentinal tubule occlusion. We used X-ray diffractometer (XRD), scanning electronic microscope (SEM), and Fourier transform infrared (FTIR) to investigate the physiochemical properties and the dentinal tubule occlusion ability of BG and MBG groups. The results showed that the major crystallite phase of MBG and BG agents was monocalcium phosphate monohydrate. MBG pastes, mixed with 30 and 40 wt% phosphoric acid hardening solutions, had the ability to create a penetration depth greater than 50 μm. These results showed that BG with mesoporous structures turned the pastes mixed with suitable phosphoric acid solution into a material with great ability for occluding dentinal tubules; it has a short reaction time and good operability, and these agents have better potential for the treatment of dentin hypersensitivity than BG without mesoporous structures.

  2. Effects of bioactive glass with and without mesoporous structures on desensitization in dentinal tubule occlusion

    International Nuclear Information System (INIS)

    Chen, Wen-Cheng; Kung, Jung-Chang; Chen, Cheng-Hwei; Hsiao, Yu-Cheng; Shih, Chi-Jen; Chien, Chi-Sheng

    2013-01-01

    Bioactive glass (BG) is a potential material for treating dentin hypersensitivity due to its high ability of dissolution. In this study, conventional BG and BG with well-ordered mesopore structures (MBG) were applied for dentinal tubule occlusion. We used X-ray diffractometer (XRD), scanning electronic microscope (SEM), and Fourier transform infrared (FTIR) to investigate the physiochemical properties and the dentinal tubule occlusion ability of BG and MBG groups. The results showed that the major crystallite phase of MBG and BG agents was monocalcium phosphate monohydrate. MBG pastes, mixed with 30 and 40 wt% phosphoric acid hardening solutions, had the ability to create a penetration depth greater than 50 μm. These results showed that BG with mesoporous structures turned the pastes mixed with suitable phosphoric acid solution into a material with great ability for occluding dentinal tubules; it has a short reaction time and good operability, and these agents have better potential for the treatment of dentin hypersensitivity than BG without mesoporous structures.

  3. Antioxidant Protection against Pathological Mycotoxins Alterations on Proximal Tubules in Rat Kidney

    Directory of Open Access Journals (Sweden)

    Susan Abdu

    2011-04-01

    Full Text Available Background: Ochratoxin A (OTA was one of the mycotoxins and received attention worldwide because of the hazard it posed to human and animal health, where the kidney was the primary target organ for OTA toxicity. In the other hand, dates served as a good source of natural antioxidants and could potentially be considered as a functional food.Methods: The study was performed in the department of biology in King Abdulaziz University. Animals were gavage administrated and divided into four groups: first group received (sodium bicarbonate, second group received (289 µg OTA /kg B.W. /day, third group received (1mg Ajwa/kg B.W. / day and fourth group received (289 µg OTA /kg B.W./day+ 1mg Ajwa /kg B.W. / day. Serum (creatinine - urea levels were measured in each group at the time of tissue collection , some biopsies were fixed in 10% buffered formalin solution for light microscopy processing stained with Haematoxylin and Eosin (H& E., Periodic Acid-Schiff (PAS and Masson´s Trichrome (M.T..Other biopsies were immediately collected into electron microscopy processing. Results: After 28 days, a significant decrease in body weight, kidney weight and relative weight was detected in OTA treated group. Also, Serum (creatinine - urea level were elevated .The normal cyto-architecture of proximal tubules were lost exhibiting damaged bruch border, degenerated, binucleated and karyomegalic cells. The most destructed ultra-structure was the mitochondria which severely swollen with disintegrated membranes. In Ajwa Date extract-group the proximal tubules were normal, whereas in Ajwa date extract + OTA -group the severity of the lesions was significantly reduced. Conclusion: The present results indicated that, Ajwa date have protective effects and ameliorated the lesions of Ochratoxin nepherotoxicity which might lead to kidney failure.

  4. Role of delta-tubulin and the C-tubule in assembly of Paramecium basal bodies

    Directory of Open Access Journals (Sweden)

    Beisson Janine

    2001-03-01

    Full Text Available Abstract Background A breakthrough in the understanding of centriole assembly was provided by the characterization of the UNI3 gene in Chlamydomonas. Deletion of this gene, found to encode a novel member of the tubulin superfamily, delta-tubulin, results in the loss of the C-tubule, in the nine microtubule triplets which are the hallmark of centrioles and basal bodies. Delta-tubulin homologs have been identified in the genomes of mammals and protozoa, but their phylogenetic relationships are unclear and their function is not yet known. Results Using the method of gene-specific silencing, we have inactivated the Paramecium delta-tubulin gene, which was recently identified. This inactivation leads to loss of the C-tubule in all basal bodies, without any effect on ciliogenesis. This deficiency does not directly affect basal body duplication, but perturbs the cortical cytoskeleton, progressively leading to mislocalization and loss of basal bodies and to altered cell size and shape. Furthermore, additional loss of B- and even A-tubules at one or more triplet sites are observed: around these incomplete cylinders, the remaining doublets are nevertheless positioned according to the native ninefold symmetry. Conclusions The fact that in two distinct phyla, delta-tubulin plays a similar role provides a new basis for interpreting phylogenetic relationships among delta-tubulins. The role of delta-tubulin in C-tubule assembly reveals that tubulins contribute subtle specificities at microtubule nucleation sites. Our observations also demonstrate the existence of a prepattern for the ninefold symmetry of the organelle which is maintained even if less than 9 triplets develop.

  5. Destruction and regeneration of seminiferous tubules after local x-irradiation of testes of the adult rats

    International Nuclear Information System (INIS)

    Kurnosova, T.R.; Rajtsina, S.S.

    1987-01-01

    It was established that the local X-irradiation (1000 R) of testes of the adult rats results in a total destruction of seminiferous tubules. The restitution of the organ structure proceeds via formation of new seminiferous tubules in which spermatogenic epithelium later develops. Rete testis and germ cells preserved in its epithelium from embryogenesis are a source of regeneration material. The results obtained favour the suggestion about the dynamic structure of mammalian testis

  6. Optimizing mission critical data dissemination in massive IoT networks

    KAUST Repository

    Farooq, Muhammad Junaid; Elsawy, Hesham; Zhu, Quanyan; Alouini, Mohamed-Slim

    2017-01-01

    Mission critical data dissemination in massive Internet of things (IoT) networks imposes constraints on the message transfer delay between devices. Due to low power and communication range of IoT devices, data is foreseen to be relayed over multiple

  7. Nicotine increases brain functional network efficiency.

    Science.gov (United States)

    Wylie, Korey P; Rojas, Donald C; Tanabe, Jody; Martin, Laura F; Tregellas, Jason R

    2012-10-15

    Despite the use of cholinergic therapies in Alzheimer's disease and the development of cholinergic strategies for schizophrenia, relatively little is known about how the system modulates the connectivity and structure of large-scale brain networks. To better understand how nicotinic cholinergic systems alter these networks, this study examined the effects of nicotine on measures of whole-brain network communication efficiency. Resting state fMRI was acquired from fifteen healthy subjects before and after the application of nicotine or placebo transdermal patches in a single blind, crossover design. Data, which were previously examined for default network activity, were analyzed with network topology techniques to measure changes in the communication efficiency of whole-brain networks. Nicotine significantly increased local efficiency, a parameter that estimates the network's tolerance to local errors in communication. Nicotine also significantly enhanced the regional efficiency of limbic and paralimbic areas of the brain, areas which are especially altered in diseases such as Alzheimer's disease and schizophrenia. These changes in network topology may be one mechanism by which cholinergic therapies improve brain function. Published by Elsevier Inc.

  8. Secure and Efficient Access Control Scheme for Wireless Sensor Networks in the Cross-Domain Context of the IoT

    Directory of Open Access Journals (Sweden)

    Ming Luo

    2018-01-01

    Full Text Available Nowadays wireless sensor network (WSN is increasingly being used in the Internet of Things (IoT for data collection, and design of an access control scheme that allows an Internet user as part of IoT to access the WSN becomes a hot topic. A lot of access control schemes have been proposed for the WSNs in the context of the IoT. Nevertheless, almost all of these schemes assume that communication nodes in different network domains share common system parameters, which is not suitable for cross-domain IoT environment in practical situations. To solve this shortcoming, we propose a more secure and efficient access control scheme for wireless sensor networks in the cross-domain context of the Internet of Things, which allows an Internet user in a certificateless cryptography (CLC environment to communicate with a sensor node in an identity-based cryptography (IBC environment with different system parameters. Moreover, our proposed scheme achieves known session-specific temporary information security (KSSTIS that most of access control schemes cannot satisfy. Performance analysis is given to show that our scheme is well suited for wireless sensor networks in the cross-domain context of the IoT.

  9. Effects of two desensitizing dentifrices on dentinal tubule occlusion with citric acid challenge: Confocal laser scanning microscopy study

    Directory of Open Access Journals (Sweden)

    Sneha Anil Rajguru

    2017-01-01

    Full Text Available Background: Dentin hypersensitivity results when patent tubules are exposed to pain-inducing external stimuli. Aim: This study aims to compare the effects of two desensitizing dentifrices containing NovaMin and arginine on dentinal tubule occlusion with and without citric acid challenge in vitro using confocal laser scanning microscopy (CLSM. Materials and Methods: Forty dentin discs were randomly divided into Groups I and II containing twenty specimens each, treated with NovaMin and arginine-containing dentifrices, respectively. Groups I and II were divided into subgroups A and B where IA and IIA underwent CLSM analysis to determine the percentage of tubule occlusion while IB and IIB underwent 0.3% citric acid challenge and CLSM analysis. A novel grading system was devised to categorize tubule occlusion. Results: In Group II, the percentage of occluded tubules was highest for IIA (72.25% ± 10.57% and least for IIB (42.55% ± 8.65% having statistical significance (P < 0.0005. In Group I, the difference between IA (49.9% ± 12.96% and IB (43.15% ± 12.43% was statistically insignificant (P = 0.249. On the comparison between IB and IIB statistically indifferent result was obtained (P = 0.901, whereas the difference between IA and IIA was statistically significant (P < 0.001. The results of grading system were for IA 50% of samples belonged to Grade 2, for IIA 60% - Grade 3, and for IB 70% and for IIB 90% - Grade 2. Conclusion: Dentinal tubule occlusion with arginine-containing dentifrice was significantly higher than NovaMin. However, it could not resist citric acid challenge as effectively as NovaMin. The effects of NovaMin were more sustainable as compared to arginine-containing dentifrice, thus proving to be a better desensitizing agent.

  10. Network centrality based team formation: A case study on T-20 cricket

    Directory of Open Access Journals (Sweden)

    Paramita Dey

    2017-07-01

    Full Text Available This paper proposes and evaluates the novel utilization of small world network properties for the formation of team of players with both best performances and best belongingness within the team network. To verify this concept, this methodology is applied to T-20 cricket teams. The players are treated as nodes of the network, whereas the number of interactions between team members is denoted as the edges between those nodes. All intra country networks form the cricket network for this case study. Analysis of the networks depicts that T-20 cricket network inherits all characteristics of small world network. Making a quantitative measure for an individual performance in the team sports is important with respect to the fact that for team selection of an International match, from pool of best players, only eleven players can be selected for the team. The statistical record of each player considered as a traditional way of quantifying the performance of a player. But the other criteria such as performing against a strong opponent or performance as an effective team member such as fielding, running between the wickets, good partnership deserves more credential. In this paper a revised method based on social networking is presented to quantify the quality of team belongingness and efficiency of each player. The application of Social Network Analysis (SNA is explored to measure performances and the rank of the players. A bidirectional weighted network of players is generated using the information collected from T-20 cricket (2014–2016 and used for network analysis. Thus team was formed based on that ranking and compared with their IPL (Indian Premier League performances of 2016.

  11. Chapitre 14. Networking Project: available S&T resources in the United States for networking with home countries

    OpenAIRE

    Johnson, Jean

    2013-01-01

    Some science and technology (S&T) policies and programs of the United States would facilitate the networking of the foreign-born scientists and engineers (S&Es) with their home countries to contribute to development. These policies and programs would mainly facilitate networking to build up S&T infrastructure. The Director of the National Science Foundation (NSF) has encouraged the U.S. science community to become even further engaged in the world, and has elevated international science withi...

  12. Disruption of Core Planar Cell Polarity Signaling Regulates Renal Tubule Morphogenesis but Is Not Cystogenic.

    Science.gov (United States)

    Kunimoto, Koshi; Bayly, Roy D; Vladar, Eszter K; Vonderfecht, Tyson; Gallagher, Anna-Rachel; Axelrod, Jeffrey D

    2017-10-23

    Oriented cell division (OCD) and convergent extension (CE) shape developing renal tubules, and their disruption has been associated with polycystic kidney disease (PKD) genes, the majority of which encode proteins that localize to primary cilia. Core planar cell polarity (PCP) signaling controls OCD and CE in other contexts, leading to the hypothesis that disruption of PCP signaling interferes with CE and/or OCD to produce PKD. Nonetheless, the contribution of PCP to tubulogenesis and cystogenesis is uncertain, and two major questions remain unanswered. Specifically, the inference that mutation of PKD genes interferes with PCP signaling is untested, and the importance of PCP signaling for cystogenic PKD phenotypes has not been examined. We show that, during proliferative stages, PCP signaling polarizes renal tubules to control OCD. However, we find that, contrary to the prevailing model, PKD mutations do not disrupt PCP signaling but instead act independently and in parallel with PCP signaling to affect OCD. Indeed, PCP signaling that is normally downregulated once development is completed is retained in cystic adult kidneys. Disrupting PCP signaling results in inaccurate control of tubule diameter, a tightly regulated parameter with important physiological ramifications. However, we show that disruption of PCP signaling is not cystogenic. Our results suggest that regulating tubule diameter is a key function of PCP signaling but that loss of this control does not induce cysts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. In-Network Data Processing in Software-Defined IoT with a Programmable Data Plane

    Directory of Open Access Journals (Sweden)

    Ki-Wook Kim

    2018-01-01

    Full Text Available Making an SDN data plane flexible enough to satisfy the various requirements of heterogeneous IoT applications is very desirable in terms of software-defined IoT (SD-IoT networking. Network devices with a programmable data plane provide an ability to dynamically add new packet- and data-processing procedures to IoT applications. The previously proposed solutions for the addition of the programmability feature to the SDN data plane provide extensibility for the packet-forwarding operations of new protocols, but IoT applications need a more flexible programmability for in-network data-processing operations (e.g., the sensing-data aggregation from thousands of sensor nodes. Moreover, some IoT models such as OMG DDS, oneM2M, and Eclipse SCADA use the publish-subscribe model that is difficult to represent using the operations of the existing message-centric data-plane models. We introduce a new in-network data-processing scheme for the SD-IoT data plane that defines an event-driven data-processing model that can express a variety of in-network data-processing cases in the SD-IoT environment. Also, the proposed model comprises a language for the programming of the data-processing procedures, while a flexible data-plane structure that can install and execute the programs at runtime is additionally presented. We demonstrate the flexibility of the proposed scheme by using sample programs in a number of example SD-IoT cases.

  14. The Single Kinin Receptor Signals to Separate and Independent Physiological Pathways in Malpighian Tubules of the Yellow Fever Mosquito

    Science.gov (United States)

    2010-06-10

    mortar and pestle . On the day of the experiment a female mosquito, 4-7 days post-eclosion, was cold anesthetized and decapitated. Malpighian tubules...tubules was analyzed with the electron probe as described previously (7, 62), except that we used the JEOL JXA 8900 EPMA Microprobe (Tokyo, Japan

  15. Study of t$\\bar{t}$ production in tau jets channel at CDFII using neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Amerio, Silvia [Univ. of Trento (Italy)

    2005-12-01

    CDF (Collider Detector at Fermilab) is a particle detector located at Fermi National Laboratories, near Chicago. it allows to study decay products of p$\\bar{p}$ collisions at center-of-mass energy of 1.96 TeV. During its first period of data taking (RunI), CDF observed for the first time the top quark (1995). The current period of data taking (RunII) is devoted to precise measurements of top properties and to search for new physics. This thesis work is about the top decay channel named τ + jets. A t$\\bar{t}$ pair decays in two W bosons and two b quarks. In a τ + jets event, one out of the two W decays into two jets of hadrons, while the other produces a τ lepton and a neutrino; the τ decays semileptonically in one or more charged and neutral pions while b quarks hadronize producing two jets of particles. Thus the final state of a τ + jets event has this specific signature: five jets, one τ-like, i.e. narrow and with low track multiplicity, two from b quarks, two from a W boson and a large amount of missing energy from two τ neutrinos. They search for this signal in 311 pb-1 of data collected with TOP{_}MULTIJET trigger. They use neural networks to separate signal from background and on the selected sample they perform a t$\\bar{t}$ production cross section measurement. The thesis is structured as follows: in Chapter 1 they outline the physics of top and τ, concentrating on their discovery, production mechanisms and current physics results involving them. Chapter 2 is devoted to the description of the experimental setup: the accelerator complex first and CDF detector then. The trigger system is described in Chapter 3, while Chapter 4 shows how particles are reconstructed exploiting information from different CDF subdetectors. With Chapter 5 they begin to present their analysis: we use a feed forward neural network based on a minimization algorithm developed in Trento University, called Reactive Taboo Search (RTS), especially designed to rapidly

  16. Study of t anti-t production in tau jets channel at CDFII using neural networks

    International Nuclear Information System (INIS)

    Amerio, Silvia

    2005-01-01

    CDF (Collider Detector at Fermilab) is a particle detector located at Fermi National Laboratories, near Chicago. it allows to study decay products of p(bar p) collisions at center-of-mass energy of 1.96 TeV. During its first period of data taking (RunI), CDF observed for the first time the top quark (1995). The current period of data taking (RunII) is devoted to precise measurements of top properties and to search for new physics. This thesis work is about the top decay channel named τ + jets. A t(bar t) pair decays in two W bosons and two b quarks. In a τ + jets event, one out of the two W decays into two jets of hadrons, while the other produces a τ lepton and a neutrino; the τ decays semileptonically in one or more charged and neutral pions while b quarks hadronize producing two jets of particles. Thus the final state of a τ + jets event has this specific signature: five jets, one τ-like, i.e. narrow and with low track multiplicity, two from b quarks, two from a W boson and a large amount of missing energy from two τ neutrinos. They search for this signal in 311 pb -1 of data collected with TOP( ) MULTIJET trigger. They use neural networks to separate signal from background and on the selected sample they perform a t(bar t) production cross section measurement. The thesis is structured as follows: in Chapter 1 they outline the physics of top and τ, concentrating on their discovery, production mechanisms and current physics results involving them. Chapter 2 is devoted to the description of the experimental setup: the accelerator complex first and CDF detector then. The trigger system is described in Chapter 3, while Chapter 4 shows how particles are reconstructed exploiting information from different CDF subdetectors. With Chapter 5 they begin to present their analysis: we use a feed forward neural network based on a minimization algorithm developed in Trento University, called Reactive Taboo Search (RTS), especially designed to rapidly escape from local

  17. Short-term PV/T module temperature prediction based on PCA-RBF neural network

    Science.gov (United States)

    Li, Jiyong; Zhao, Zhendong; Li, Yisheng; Xiao, Jing; Tang, Yunfeng

    2018-02-01

    Aiming at the non-linearity and large inertia of temperature control in PV/T system, short-term temperature prediction of PV/T module is proposed, to make the PV/T system controller run forward according to the short-term forecasting situation to optimize control effect. Based on the analysis of the correlation between PV/T module temperature and meteorological factors, and the temperature of adjacent time series, the principal component analysis (PCA) method is used to pre-process the original input sample data. Combined with the RBF neural network theory, the simulation results show that the PCA method makes the prediction accuracy of the network model higher and the generalization performance stronger than that of the RBF neural network without the main component extraction.

  18. Scattering of neutrons by catalase: a study of molecules, subunits, and tubules

    International Nuclear Information System (INIS)

    Randall, J.; Starling, D.; Baldwin, J.P.; Ibel, K.

    1976-01-01

    The paper deals with small-angle scattering of neutrons by catalase tetramers, dimers, and monomers and with neutron diffraction by helical assemblies of tetramers in the form of tubules. A preliminary study of catalase is described

  19. A de novo transcriptome of the Malpighian tubules in non-blood-fed and blood-fed Asian tiger mosquitoes Aedes albopictus: insights into diuresis, detoxification, and blood meal processing

    Directory of Open Access Journals (Sweden)

    Carlos J. Esquivel

    2016-03-01

    Malpighian tubules, respectively, to confirm that the transcriptomic changes were associated with functional consequences. In particular, in vivo diuresis assays demonstrated that adult female mosquitoes have a reduced diuretic capacity within 24 h after a blood meal. Moreover, biochemical assays in isolated Malpighian tubules showed an increase in glutathione S-transferase activity and the accumulation of uric acid (an end product of purine catabolism within 24 h after a blood meal. Our data provide new insights into the molecular physiology of Malpighian tubules in culicine mosquitoes and reveal potentially important molecular targets for the development of chemical and/or gene-silencing insecticides that would disrupt renal function in mosquitoes.

  20. Network Security Issues in The Internet of Things (IoT)

    OpenAIRE

    Millar, Stuart

    2016-01-01

    This paper surveys a broad range of other research works in order to discuss network security issues in the Internet of Things (IoT). We begin with setting the scene generally with an outline of IoT, followed by a discussion of IoT layer models and topologies. After this, IoT standardization efforts and protocols are analysed, before we discuss in depth vulnerabilities, attacks and mitigations with regard IoT. It is concluded that ample research and narrative exists for protocols and vulnerab...

  1. Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL.

    Science.gov (United States)

    Della Gatta, Giusy; Palomero, Teresa; Perez-Garcia, Arianne; Ambesi-Impiombato, Alberto; Bansal, Mukesh; Carpenter, Zachary W; De Keersmaecker, Kim; Sole, Xavier; Xu, Luyao; Paietta, Elisabeth; Racevskis, Janis; Wiernik, Peter H; Rowe, Jacob M; Meijerink, Jules P; Califano, Andrea; Ferrando, Adolfo A

    2012-02-26

    The TLX1 and TLX3 transcription factor oncogenes have a key role in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). Here we used reverse engineering of global transcriptional networks to decipher the oncogenic regulatory circuit controlled by TLX1 and TLX3. This systems biology analysis defined T cell leukemia homeobox 1 (TLX1) and TLX3 as master regulators of an oncogenic transcriptional circuit governing T-ALL. Notably, a network structure analysis of this hierarchical network identified RUNX1 as a key mediator of the T-ALL induced by TLX1 and TLX3 and predicted a tumor-suppressor role for RUNX1 in T cell transformation. Consistent with these results, we identified recurrent somatic loss-of-function mutations in RUNX1 in human T-ALL. Overall, these results place TLX1 and TLX3 at the top of an oncogenic transcriptional network controlling leukemia development, show the power of network analyses to identify key elements in the regulatory circuits governing human cancer and identify RUNX1 as a tumor-suppressor gene in T-ALL.

  2. Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules.

    Science.gov (United States)

    Armour, Eric A; Carson, Robert P; Ess, Kevin C

    2012-08-15

    Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia.

  3. Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules

    Science.gov (United States)

    Armour, Eric A.; Carson, Robert P.

    2012-01-01

    Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia. PMID:22674026

  4. Locally formed dopamine inhibits Na sup + -K sup + -ATPase activity in rat renal cortical tubule cells

    Energy Technology Data Exchange (ETDEWEB)

    Seri, I.; Kone, B.C.; Gullans, S.R.; Aperia, A.; Brenner, B.M.; Ballermann, B.J. (Harvard Medical School, Boston, MA (USA) Karolinska Institute, Stockholm (Sweden))

    1988-10-01

    Dopamine, generated locally from L-dopa, inhibits Na{sup +}-K{sup +}-ATPase in permeabilized rat proximal tubules under maximum transport rate conditions for sodium. To determine whether locally formed dopamine inhibits Na{sup +}-K{sup +}-ATPase activity in intact cortical tubule cells we studied the effect of L-dopa on ouabain-sensitive oxygen consumption rate ({dot Q}o{sub 2}) and {sup 86}Rb uptake in renal cortical tubule cell suspensions. L-Dopa did not affect ouabain-insensitive {dot Q}o{sub 2} or mitochondrial respiration. However, L-dopa inhibited ouabain-sensitive {dot Q}o{sub 2} in a concentration-dependent manner, with half-maximal inhibition (K{sub 0.5}) of 5 {times} 10{sup {minus}7} M and a maximal inhibition of 14.1 {plus minus} 1.5% at 10{sup {minus}4}M. L-Dopa also blunted the nystatin-stimulated {dot Q}o{sub 2} in a concentration-dependent manner, indicating the L-dopa directly inhibits Na{sup +}-K{sup +}-ATPase activity and not sodium entry. Ouabain-sensitive {sup 86}Rb uptake was also inhibited by L-dopa. Carbidopa, an inhibitor of the conversion of L-dopa to dopamine, eliminated the effect of L-dopa on ouabain-sensitive {dot Q}o{sub 2} and {sup 86}Rb uptake, indicating that dopamine rather than L-dopa was the active agent. The finding that the L-dopa concentration-response curve was shifted to the left by one order of magnitude in the presence of nystatin suggests that the inhibitory effect is enhanced when the intracellular sodium concentration is increased. By studying the effect of L-dopa on ouabain-sensitive {dot Q}o{sub 2} at increasing extracellular sodium concentrations in the presence of nystatin, the authors demonstrated that the inhibitory effect of locally formed dopamine on the Na{sup +}-K{sup +}-ATPase is indeed dependent on the sodium available for the enzyme and occurs in an uncompetitive manner.

  5. T-wave end detection using neural networks and Support Vector Machines.

    Science.gov (United States)

    Suárez-León, Alexander Alexeis; Varon, Carolina; Willems, Rik; Van Huffel, Sabine; Vázquez-Seisdedos, Carlos Román

    2018-05-01

    In this paper we propose a new approach for detecting the end of the T-wave in the electrocardiogram (ECG) using Neural Networks and Support Vector Machines. Both, Multilayer Perceptron (MLP) neural networks and Fixed-Size Least-Squares Support Vector Machines (FS-LSSVM) were used as regression algorithms to determine the end of the T-wave. Different strategies for selecting the training set such as random selection, k-means, robust clustering and maximum quadratic (Rényi) entropy were evaluated. Individual parameters were tuned for each method during training and the results are given for the evaluation set. A comparison between MLP and FS-LSSVM approaches was performed. Finally, a fair comparison of the FS-LSSVM method with other state-of-the-art algorithms for detecting the end of the T-wave was included. The experimental results show that FS-LSSVM approaches are more suitable as regression algorithms than MLP neural networks. Despite the small training sets used, the FS-LSSVM methods outperformed the state-of-the-art techniques. FS-LSSVM can be successfully used as a T-wave end detection algorithm in ECG even with small training set sizes. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Vitality of Enterococcus faecalis inside dentinal tubules after five root canal disinfection methods.

    Science.gov (United States)

    Vatkar, Niranjan Ashok; Hegde, Vivek; Sathe, Sucheta

    2016-01-01

    To compare the vitality of Enterococcus faecalis within dentinal tubules after subjected to five root canal disinfection methods. Dentin blocks (n = 60) were colonized with E. faecalis. After 4 weeks of incubation, the dentin blocks were divided into one control and five test groups (n = 10 each). The root canals of test groups were subjected to one of the disinfection methods, namely, normal saline (NS), sodium hypochlorite (NaOCl), chlorhexidine digluconate (CHX), neodymium-doped yttrium aluminum garnet (Nd: YAG) laser, and diode laser. The effect of disinfection methods was assessed by LIVE/DEAD BacLight stain under the confocal laser scanning microscopy to determine the "zone of dead bacteria" (ZDB). Mean values were calculated for ZDB and the difference between groups was established. Penetration of E. faecalis was seen to a depth of >1000 μm. Viable bacteria were detected with NS irrigation. NaOCl and CHX showed partial ZDB. When the root canals were disinfected with Nd: YAG and diode lasers, no viable bacteria were found. E. faecalis has the ability to colonize inside dentinal tubules to a depth of >1000 μm. In contrast to conventional irrigants, both Nd: YAG and diode lasers were effective in eliminating the vitality of E. faecalis. NS, NaOCl, and CHX showed viable bacteria remaining in dentinal tubules.

  7. Ribavirin exposure induces histopathological changes in the seminiferous tubules of testes in albino rats

    International Nuclear Information System (INIS)

    Batool, A.

    2013-01-01

    Study objectives: The objectives of the study are to describe and compare histopathological changes in the seminiferous tubules of testes of rat, with different doses of Ribavirin at different time intervals. Introduction: The chemical disturbances may affect a vast number of potential sites in male reproductive system as well as its complex hormonal regulation. Testicular toxicity may reduce the fertility of the male. The current study was conducted to evaluate the effects of Ribavirin on the histological structure of seminiferous tubules in the testes of albino rats. Materials and Methods: Seventy two sexually mature adult male albino rats weighing 180-200gms were divided into four groups: A, B, C and D; each group having 18 rats. Ribavirin was administered intraperitoneally in different doses to these groups that were 20mg, 100mg and 200mg/kg body weight, while group A was control. Each group was further divided into three subgroups according to three time points which were selected for sacrifice that were 20th, 40th and 60th day from the last exposure to drug. Six randomly selected rats from each group were sacrificed on every sacrifice time. Results and Conclusion: The seminiferous tubules with degenerative changes like appearance of vacuole and necrotic material were observed in comparison to control groups, on 20th day of sacrifice in all groups. In rats sacrificed on day 40th and 60th, the sign of recovery in the form of regeneration of seminiferous epithelium was observed that was more marked in low dose groups than high dose groups which showed late recovery. We conclude that ribavirin being used as antiviral drug induces reversible degenerative changes in the seminiferous tubules of testes of albino rats. (author)

  8. Leveraging Fog Computing for Scalable IoT Datacenter Using Spine-Leaf Network Topology

    Directory of Open Access Journals (Sweden)

    K. C. Okafor

    2017-01-01

    Full Text Available With the Internet of Everything (IoE paradigm that gathers almost every object online, huge traffic workload, bandwidth, security, and latency issues remain a concern for IoT users in today’s world. Besides, the scalability requirements found in the current IoT data processing (in the cloud can hardly be used for applications such as assisted living systems, Big Data analytic solutions, and smart embedded applications. This paper proposes an extended cloud IoT model that optimizes bandwidth while allowing edge devices (Internet-connected objects/devices to smartly process data without relying on a cloud network. Its integration with a massively scaled spine-leaf (SL network topology is highlighted. This is contrasted with a legacy multitier layered architecture housing network services and routing policies. The perspective offered in this paper explains how low-latency and bandwidth intensive applications can transfer data to the cloud (and then back to the edge application without impacting QoS performance. Consequently, a spine-leaf Fog computing network (SL-FCN is presented for reducing latency and network congestion issues in a highly distributed and multilayer virtualized IoT datacenter environment. This approach is cost-effective as it maximizes bandwidth while maintaining redundancy and resiliency against failures in mission critical applications.

  9. Regulation of MRP2-mediated transport in shark rectal salt gland tubules.

    NARCIS (Netherlands)

    Miller, D.S.; Masereeuw, R.; Karnaky Jr, K.J.

    2002-01-01

    We examined endothelin-1 (ET-1) regulation of the xenobiotic efflux pump, multidrug resistance-associated protein isoform 2 (MRP2), in intact dogfish shark rectal salt gland tubules using a fluorescent substrate sulforhodamine 101 and confocal microscopy. Subnanomolar to nanomolar concentrations of

  10. Efficacy of Modified Bioactive Glass for Dentin Remineralization and Obstruction of Dentinal Tubules

    Directory of Open Access Journals (Sweden)

    Mahshid Saffarpour

    2017-10-01

    Full Text Available Objectives: This study assessed the efficacy of modified bioactive glass (MBG for dentin remineralization and obstruction of dentinal tubules.Materials and Methods: Thirty-six dentin discs were made from 20 third molars and were stored in 12% lactic acid solution for two weeks to induce demineralization. The samples were divided into three groups (n=12: 1- BG, 2- BG modified with 5% strontium (Sr and 3- BG modified with 10% Sr. After applying the BG, the samples were stored in artificial saliva for 7, 14 and 21 days. Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR, X-ray Diffraction (XRD analysis, Scanning Electron Microscopy (SEM, and Energy-Dispersive X-ray (EDX analysis were used to assess remineralization. Also, 6 dentin discs were divided into three groups of BG, BG modified with 5% Sr and BG modified with 10% Sr, to examine tubular occlusion. The discs were etched using 0.5M of EDTA for two minutes and were stored in artificial saliva for 7 days. Changes in dentin surface morphology were evaluated under SEM.Results: Group 3 showed high rates of remineralization at days 7 and 14, although the rate decreased at day 21. Group 2 exhibited high rates of remineralization at days 7, 14 and 21. Dentinal tubules were partially occluded by BG and BG modified with 5% Sr, while they were almost completely obstructed after the use of BG modified with 10% Sr.Conclusions: Strontium increases remineralization. Addition of 10% Sr to BG enhances apatite formation; however, the apatite dissolves over time. Addition of 5% Sr to BG stabilizes the apatite lattice and increases the remineralization.

  11. Dancing with the Stars: Using Image Analysis to Study the Choreography of the Endoplasmic Reticulum and Its Partners and of Movement Within Its Tubules.

    Science.gov (United States)

    Griffing, Lawrence R

    2018-01-01

    In this chapter, approaches to the image analysis of the choreography of the plant endoplasmic reticulum (ER) labeled with fluorescent fusion proteins ("stars," if you wish) are presented. The approaches include the analyses of those parts of the ER that are attached through membrane contact sites to moving or nonmoving partners (other "stars"). Image analysis is also used to understand the nature of the tubular polygonal network, the hallmark of this organelle, and how the polygons change over time due to tubule sliding or motion. Furthermore, the remodeling polygons of the ER interact with regions of fundamentally different topology, the ER cisternae, and image analysis can be used to separate the tubules from the cisternae. ER cisternae, like polygons and tubules, can be motile or stationary. To study which parts are attached to nonmoving partners, such as domains of the ER that form membrane contact sites with the plasma membrane/cell wall, an image analysis approach called persistency mapping has been used. To study the domains of the ER that are moving rapidly and streaming through the cell, the image analysis of optic flow has been used. However, optic flow approaches confuse the movement of the ER itself with the movement of proteins within the ER. As an overall measure of ER dynamics, optic flow approaches are of value, but their limitation as to what exactly is "flowing" needs to be specified. Finally, there are important imaging approaches that directly address the movement of fluorescent proteins within the ER lumen or in the membrane of the ER. Of these, fluorescence recovery after photobleaching (FRAP), inverse FRAP (iFRAP), and single particle tracking approaches are described.

  12. Effects of lead intoxication on intercellular junctions and biochemical alterations of the renal proximal tubule cells.

    Science.gov (United States)

    Navarro-Moreno, L G; Quintanar-Escorza, M A; González, S; Mondragón, R; Cerbón-Solorzáno, J; Valdés, J; Calderón-Salinas, J V

    2009-10-01

    Lead intoxication is a worldwide health problem which frequently affects the kidney. In this work, we studied the effects of chronic lead intoxication (500 ppm of Pb in drinking water during seven months) on the structure, function and biochemical properties of rat proximal tubule cells. Lead-exposed animals showed increased lead concentration in kidney, reduction of calcium and amino acids uptake, oxidative damage and glucosuria, proteinuria, hematuria and reduced urinary pH. These biochemical and physiological alterations were related to striking morphological modifications in the structure of tubule epithelial cells and in the morphology of their mitochondria, nuclei, lysosomes, basal and apical membranes. Interestingly, in addition to the nuclei, inclusion bodies were found in the cytoplasm and in mitochondria. The epithelial cell structure modifications included an early loss of the apical microvillae, followed by a decrement of the luminal space and the respective apposition and proximity of apical membranes, resulting in the formation of atypical intercellular contacts and adhesion structures. Similar but less marked alterations were observed in subacute lead intoxication as well. Our work contributes in the understanding of the physiopathology of lead intoxication on the structure of renal tubular epithelial cell-cell contacts in vivo.

  13. Cystine uptake by cultured cells originating from dog proximal tubule segments

    International Nuclear Information System (INIS)

    States, B.; Reynolds, R.; Lee, J.; Segal, S.

    1990-01-01

    Large numbers of kidney epithelial cells were cultured successfully from isolated dog proximal tubule segments. Cells in primary culture and in first passage retained the cystine-dibasic amino acid co-transporter system which is found in vivo and in freshly isolated proximal tubule segments. In contrast to other cultured cells, the cystine-glutamate anti-porter was absent in primary cultures. However, this anti-porter system seemed to be developing in cells in first passage. The intracellular ratio of cysteine:reduced glutathione (CSH:GSH) was maintained at 1:36 in both primary cultures and in low passage cells. Incubation of cells in primary culture for 5 min at 37 degrees C with 0.025 mM [ 35 S]L-cystine resulted in incorporation of approximately 36 and 8.5% of the label into intracellular CSH and GSH, respectively. These cultured cells, therefore, seem to be an excellent model system for the eventual elucidation of (a) the inticacies of cystine metabolism and (b) regulation of (1) the cystine-dibasic amino acid co-transporter system and (2) the development of the cysteine-glutamate anti-porter system

  14. Alpha/Theta Neurofeedback Increases Mentalization and Default Mode Network Connectivity in a Non-Clinical Sample.

    Science.gov (United States)

    Imperatori, Claudio; Della Marca, Giacomo; Amoroso, Noemi; Maestoso, Giulia; Valenti, Enrico Maria; Massullo, Chiara; Carbone, Giuseppe Alessio; Contardi, Anna; Farina, Benedetto

    2017-11-01

    Several studies showed the effectiveness of alpha/theta (A/T) neurofeedback training in treating some psychiatric conditions. Despite the evidence of A/T effectiveness, the psychological and neurobiological bases of its effects is still unclear. The aim of the present study was to explore the usefulness of the A/T training in increasing mentalization in a non-clinical sample. The modifications of electroencephalographic (EEG) functional connectivity in Default Mode Network (DMN) associated with A/T training were also investigated. Forty-four subjects were enrolled in the study and randomly assigned to receive ten sessions of A/T training [neurofeedback group (NFG) = 22], or to act as controls [waiting list group (WLG) = 22]. All participants were administered the mentalization questionnaire (MZQ) and the Symptom Checklist-90-Revised (SCL-90-R). In the post training assessment, compared to WLG, NFG showed a significant increase of MZQ total scores (3.94 ± 0.73 vs. 3.53 ± 0.77; F 1;43 = 8.19; p = 0.007; d = 0.863). Furthermore, A/T training was also associated with a significant increase of EEG functional connectivity in several DMN brain areas (e.g. Posterior Cingulate Cortex). Taken together our results support the usefulness of the A/T training in enhancing mentalization and DMN connectivity.

  15. A Measurement of $t\\bar{t}$Production Cross Section in $p\\bar{p}$ Collisions at $\\sqrt{s}$ = 1.8 TeV Using Neural Networks

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Harpreet [UC, Riverside

    1999-01-01

    We present the results of a new measurement of the $t\\bar{t}$ production cross section using eμ channel in pp collisions at $\\sqrt{s}$= 1.8 TeV. This study corresponds to an integrated luminosity of 108.3 ± 5.7 $pb^{-1}$ acquired by the D0 detector during the Fermilab Tevatron Collider Run I (1992-1996). By using neural network techniques instead of the conventional analysis methods, we show that the signal acceptance can be increased by 10% (for $m_t$ = 172 GeV /$c^2$ ) while the background remains constant. Four eμ events are observed in data with an estimated background of 0.22 ± 0.14 corresponding to a $t\\bar{t}$ production cross section of 9.75 ± 5.53 pb.

  16. Immortalization of canine adipose-derived mesenchymal stem cells and their seminiferous tubule transplantation.

    Science.gov (United States)

    Fang, Jia; Wei, Yudong; Teng, Xin; Zhao, Shanting; Hua, Jinlian

    2018-04-01

    Adipose-derived mesenchymal stem cells (ADSCs) are proven to provide good effects in numerous tissue engineering application and other cell-based therapies. However, the difficulty in the proliferation of ADSCs, known as the "Hayflick limit" in vitro, limits their clinical application. Here, we immortalized canine ADSCs (cADSCs) with SV40 gene and transplanted them into busulfan-induced seminiferous tubules of infertile mice. The proliferation of these immortalized cells was improved significantly. Then, cellular differentiation assays showed that the immortalized cADSCs could differentiate into three-germ-layer cells, osteogenesis, chondrogenesis, adipogenesis phenotypes, and primordial germ cell-like cells (PGCLCs). In addition, the immortalized cADSCs can proliferate in the busulfan-induced seminiferous tubules of infertile mice. These findings confirmed that the immortalized cADSCs maintain the criteria of cADSCs. © 2017 Wiley Periodicals, Inc.

  17. Does stimulation of NaCl secretion in in vitro perfused rectal gland tubules of Squalus acanthias increase membrane capacitance?

    Science.gov (United States)

    Greger, R; Thiele, I; Warth, R; Bleich, M

    1998-07-01

    NaCl secretion in rectal gland tubules (RGT) of Squalus acanthias requires the activation of Cl– channels in the luminal membrane. The RGT and its mechanism of activation are an early evolutionary paradigm of exocrine secretion. The respective Cl– channels probably resemble the shark equivalent of the cystic fibrosis transmembrane conductance regulator (CFTR). Activation of these Cl– channels occurs via cAMP. It has been hypothesized that the activation of CFTR occurs via exocytosis or inhibited endocytosis. To examine this question directly by electrical measurements we have performed whole-cell patch-clamp analyses of in vitro perfused RGT. NaCl secretion was stimulated by a solution (Stim) containing forskolin (10 µmol/l), dibutyryl-cAMP (0.5 mmol/l) and adenosine (0.5 mmol/l). This led to the expected strong depolarization and an increase in membrane conductance (G m). The membrane capacitance (C m) was measured by a newly devised two-frequency synchronous detector method. It was increased by Stim significantly from 5.00±0.22 to 5.17±0.21 pF (n=50). The increase in C m correlated with the increase in G m with a slope of 51 fF/nS. Next the effect of furosemide (500 µmol/l) was examined in previously stimulated RGT. Furosemide was supposed to inhibit coupled Na+2Cl–K+ uptake and to reduce cell volume but not membrane trafficking of Cl– channels. Furosemide reduced G m slightly (due to the fall in cytosolic Cl– concentration) and C m to the same extent by which Stim had increased it. Both changes were statistically significant, and the slope of ΔC m/ΔG m was similar to that caused by Stim. Inhibitors of microtubules or actin (colchicine, phalloidin and cytochalasin D added at 10 µmol/l to the pipette solution and dialysed for >10 min) did not alter cell voltage, G m or C m, nor did these inhibitors abolish the stimulatory effect of cAMP. These data suggest that the small C m changes observed with Stim reflect a minor cell volume increase and an

  18. Vestigial preference functions in neural networks and túngara frogs.

    OpenAIRE

    Phelps, S. M.; Ryan, M. J.; Rand, A. S.

    2001-01-01

    Although there is a growing interest in understanding how perceptual mechanisms influence behavioral evolution, few studies have addressed how perception itself is shaped by evolutionary forces. We used a combination of artificial neural network models and behavioral experiments to investigate how evolutionary history influenced the perceptual processes used in mate choice by female túngara frogs. We manipulated the evolutionary history of artificial neural network models and observed an emer...

  19. Shape transitions in anisotropic multicomponent lipid tubules

    Directory of Open Access Journals (Sweden)

    Tim eAtherton

    2016-05-01

    Full Text Available Abstract Ternary mixtures of saturated and unsaturated lipids together with cholesterol can be induced to phase separate by photo-peroxidation into lipid-ordered Lo and lipid-disordered Ld domains. Because these have different mechanical properties, the phase separation is accompanied by dramatic changes in morphology. This work considers a tubule composed of Ld phase with Lo phase inclusions that possess greater rigidity; this system has been shown experimentally by Yuan and coworkers to spontaneously adopt either banded or disc configurations following phase separation. The static behaviour of inter-domain interactions is analyzed in each of these geometries by solving the linearized shape equations. These calculations suggest a possible mechanism by which the two structures form.

  20. Fabrication and characterization of dendrimer-functionalized nano-hydroxyapatite and its application in dentin tubule occlusion.

    Science.gov (United States)

    Lin, Xuandong; Xie, Fangfang; Ma, Xueling; Hao, Yuhong; Qin, Hejia; Long, Jindong

    2017-06-01

    The occlusion of dentinal tubules is an effective method to alleviate the symptoms of dentin hypersensitivity. In this paper, we successfully modified nano-hydroxyapatite (n-HAP) with carboxyl-terminated polyamidoamine dendrimers by an aqueous-based chemical method and verified by fourier transform infrared spectroscopy (FTIR) and transmission electron microscope (TEM). Then the demineralization dentin discs were randomly divided into 4 groups, corresponding to subsequent brushing experiments: deionized water and kept in artificial saliva (AS), dendrimer-functionalized n-HAP and stored in AS, n-HAP and saved in AS, dendrimer-functionalized n-HAP and stored in deionized water. After 7 days of simulated brushing, dentin discs followed the in vitro characterization using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy and microhardness test. These data suggested that dendrimer-functionalized n-HAP could crosslink with collagen fibers and resulted in effective dentinal tubule occlusion. Moreover, the new material can induce the HAP formation with the help of superficial carboxyl and fill the spaces in dentinal tubules furtherly. The microhardness of dendrimer-functionalized n-HAP-treated specimens was significantly higher than others. In summary, dendrimer-functionalized n-HAP can be a new therapeutic material for the treatment of dentin hypersensitivity.

  1. Sodium bicarbonate cotransporter NBCe2 gene variants increase sodium and bicarbonate transport in human renal proximal tubule cells.

    Science.gov (United States)

    Gildea, John J; Xu, Peng; Kemp, Brandon A; Carlson, Julia M; Tran, Hanh T; Bigler Wang, Dora; Langouët-Astrié, Christophe J; McGrath, Helen E; Carey, Robert M; Jose, Pedro A; Felder, Robin A

    2018-01-01

    Salt sensitivity of blood pressure affects >30% of the hypertensive and >15% of the normotensive population. Variants of the electrogenic sodium bicarbonate cotransporter NBCe2 gene, SLC4A5, are associated with increased blood pressure in several ethnic groups. SLC4A5 variants are also highly associated with salt sensitivity, independent of hypertension. However, little is known about how NBCe2 contributes to salt sensitivity, although NBCe2 regulates renal tubular sodium bicarbonate transport. We hypothesized that SLC4A5 rs10177833 and rs7571842 increase NBCe2 expression and human renal proximal tubule cell (hRPTC) sodium transport and may be a cause of salt sensitivity of blood pressure. To characterize the hRPTC ion transport of wild-type (WT) and homozygous variants (HV) of SLC4A5. The expressions of NBCe2 mRNA and protein were not different between hRPTCs carrying WT or HV SLC4A5 before or after dopaminergic or angiotensin (II and III) stimulation. However, luminal to basolateral sodium transport, NHE3 protein, and Cl-/HCO3- exchanger activity in hRPTCs were higher in HV than WT SLC4A5. Increasing intracellular sodium enhanced the apical location of NBCe2 in HV hRPTCs (4.24±0.35% to 11.06±1.72% (P<0.05, N = 3, 2-way ANOVA, Holm-Sidak test)) as determined by Total Internal Reflection Fluorescence Microscopy (TIRFM). In hRPTCs isolated from kidney tissue, increasing intracellular sodium enhanced bicarbonate-dependent pH recovery rate and increased NBCe2 mRNA and protein expressions to a greater extent in HV than WT SLC4A5 (+38.00±6.23% vs HV normal salt (P<0.01, N = 4, 2-way ANOVA, Holm-Sidak test)). In hRPTCs isolated from freshly voided urine, bicarbonate-dependent pH recovery was also faster in those from salt-sensitive and carriers of HV SLC4A5 than from salt-resistant and carriers of WT SLC4A5. The faster NBCe2-specific bicarbonate-dependent pH recovery rate in HV SCL4A5 was normalized by SLC4A5- but not SLC4A4-shRNA. The binding of purified hepatocyte

  2. A measurement of t$\\bar{t}$ production cross section in p$\\bar{p}$ collisions at √s = 1.8 TeV using neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Harpreet [Univ. of California, Riverside, CA (United States)

    1999-12-01

    The authors present the results of a new measurement of the t$\\bar{t}$ production cross section using eμ channel in p$\\bar{p}$ collisions at √s = 1.8 TeV. This study corresponds to an integrated luminosity of 108.3 ± 5.7 pb-1 acquired by the D0 detector during the Fermilab Tevatron Collider Run 1 (1992--1996). By using neural network techniques instead of the conventional analysis methods, the authors show that the signal acceptance can be increased by 10% (for mt = 172 GeV/c2) while the background remains constant. Four eμ events are observed in data with an estimated background of 0.22 ± 0.14 corresponding to a t$\\bar{t}$ production cross section of 9.75 ± 5.53 pb.

  3. A telomerase immortalized human proximal tubule cell line with a truncation mutation (Q4004X in polycystin-1.

    Directory of Open Access Journals (Sweden)

    Brittney-Shea Herbert

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is associated with a variety of cellular phenotypes in renal epithelial cells. Cystic epithelia are secretory as opposed to absorptive, have higher proliferation rates in cell culture and have some characteristics of epithelial to mesenchymal transitions. In this communication we describe a telomerase immortalized cell line that expresses proximal tubule markers and is derived from renal cysts of an ADPKD kidney. These cells have a single detectable truncating mutation (Q4004X in polycystin-1. These cells make normal appearing but shorter cilia and fail to assemble polycystin-1 in the cilia, and less uncleaved polycystin-1 in membrane fractions. This cell line has been maintained in continuous passage for over 35 passages without going into senescence. Nephron segment specific markers suggest a proximal tubule origin for these cells and the cell line will be useful to study mechanistic details of cyst formation in proximal tubule cells.

  4. Tractable Stochastic Geometry Model for IoT Access in LTE Networks

    KAUST Repository

    Gharbieh, Mohammad; Elsawy, Hesham; Bader, Ahmed; Alouini, Mohamed-Slim

    2017-01-01

    The Internet of Things (IoT) is large-scale by nature. This is not only manifested by the large number of connected devices, but also by the high volumes of traffic that must be accommodated. Cellular networks are indeed a natural candidate for the data tsunami the IoT is expected to generate in conjunction with legacy human-type traffic. However, the random access process for scheduling request represents a major bottleneck to support IoT via LTE cellular networks. Accordingly, this paper develops a mathematical framework to model and study the random access channel (RACH) scalability to accommodate IoT traffic. The developed model is based on stochastic geometry and discrete time Markov chains (DTMC) to account for different access strategies and possible sources of inter-cell and intra-cell interferences. To this end, the developed model is utilized to assess and compare three different access strategies, which incorporate a combination of transmission persistency, back-off, and power ramping. The analysis and the results showcased herewith clearly illustrate the vulnerability of the random access procedure as the IoT intensity grows. Finally, the paper offers insights into effective scenarios for each transmission strategy in terms of IoT intensity and RACH detection thresholds.

  5. Tractable Stochastic Geometry Model for IoT Access in LTE Networks

    KAUST Repository

    Gharbieh, Mohammad

    2017-02-07

    The Internet of Things (IoT) is large-scale by nature. This is not only manifested by the large number of connected devices, but also by the high volumes of traffic that must be accommodated. Cellular networks are indeed a natural candidate for the data tsunami the IoT is expected to generate in conjunction with legacy human-type traffic. However, the random access process for scheduling request represents a major bottleneck to support IoT via LTE cellular networks. Accordingly, this paper develops a mathematical framework to model and study the random access channel (RACH) scalability to accommodate IoT traffic. The developed model is based on stochastic geometry and discrete time Markov chains (DTMC) to account for different access strategies and possible sources of inter-cell and intra-cell interferences. To this end, the developed model is utilized to assess and compare three different access strategies, which incorporate a combination of transmission persistency, back-off, and power ramping. The analysis and the results showcased herewith clearly illustrate the vulnerability of the random access procedure as the IoT intensity grows. Finally, the paper offers insights into effective scenarios for each transmission strategy in terms of IoT intensity and RACH detection thresholds.

  6. A bioartificial renal tubule device embedding human renal stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Anna Giovanna Sciancalepore

    Full Text Available We present a bio-inspired renal microdevice that resembles the in vivo structure of a kidney proximal tubule. For the first time, a population of tubular adult renal stem/progenitor cells (ARPCs was embedded into a microsystem to create a bioengineered renal tubule. These cells have both multipotent differentiation abilities and an extraordinary capacity for injured renal cell regeneration. Therefore, ARPCs may be considered a promising tool for promoting regenerative processes in the kidney to treat acute and chronic renal injury. Here ARPCs were grown to confluence and exposed to a laminar fluid shear stress into the chip, in order to induce a functional cell polarization. Exposing ARPCs to fluid shear stress in the chip led the aquaporin-2 transporter to localize at their apical region and the Na(+K(+ATPase pump at their basolateral portion, in contrast to statically cultured ARPCs. A recovery of urea and creatinine of (20±5% and (13±5%, respectively, was obtained by the device. The microengineered biochip here-proposed might be an innovative "lab-on-a-chip" platform to investigate in vitro ARPCs behaviour or to test drugs for therapeutic and toxicological responses.

  7. Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism

    NARCIS (Netherlands)

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E.; Lamers, Wouter H.; Chaudhry, Farrukh A.; Verlander, Jill W.; Weiner, I. David

    2016-01-01

    Glutamine synthetase (GS) catalyzes the recycling of NH4 (+) with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of

  8. [Anatomy, physiology and clinical relevance of the connecting tubule].

    Science.gov (United States)

    Miranda, N; Simeoni, M A; Ciriana, E; Panico, C; Cappello, E; Capasso, G B

    2009-01-01

    The cortical distal nephron is the site of fine regulation of salt and water excretion by peptide and mineralocorticoid hormones and the site for specific actions of diuretics. Some data suggest that sodium reabsorption and potassium secretion in the distal convoluted tubule and the connecting tubule (CNT) are sufficient to maintain the sodium and potassium balance, with little or no contribution of the collecting duct. The homeostatic role of the sodium and potassium transport systems in the collecting duct can be questioned, especially in conditions where dietary sodium intake is high and potassium intake is low compared with the physiological needs of the organism. The functional expression of epithelial sodium channels (ENaC) in the CNT is sufficient for furosemide-stimulated urinary acidification and identifies the CNT as a major segment in electrogenic urinary acidification. In the outer renal cortex, the CNT returns to the glomerular hilus and contacts the renal afferent arterioles (Af-Art). This morphology is compatible with a cross-talk between the CNT and Af-Art. This novel regulatory mechanism of the renal microcirculation may participate in the vasodilatation observed during high salt intake, perhaps by antagonizing tubuloglomerular feedback. In conclusion, the cortical distal nephron appears to be a complex site for several physiological mechanisms; it is mainly involved in salt and fluid homeostasis and in acid-base balance maintenance. Furthermore, the CNT segment appears to promote a CNT-Af-Art feedback loop.

  9. Higher Physical Activity is Associated with Increased Attentional Network Connectivity in the Healthy Elderly

    Directory of Open Access Journals (Sweden)

    Geon Ha Kim

    2016-08-01

    Full Text Available The purpose of this study was to demonstrate the potential alterations in structural network properties related to physical activity (PA in healthy elderly. We recruited 76 elderly individuals with normal cognition from Samsung Medical Center in Seoul, Korea. All participants underwent the Cambridge Neuropsychological Test Automated Battery and 3.0T brain magnetic resonance imaging (MRI. Participants were subdivided into quartiles according to the International Physical Activity Questionnaire scores, which represents the amount of PA. Through graph theory based analyses, we compared global and local network topologies according to PA quartile. The higher PA group demonstrated better performance in speed processing compared to the lower PA group. Regional nodal strength also significantly increased in the higher PA group, which involved the bilateral middle frontal, bilateral inferior parietal, right medial orbitofrontal, right superior and middle temporal gyri. These results were further replicated when the highest and the lowest quartile groups were compared in terms of regional nodal strengths and local efficiency. Our findings that the regional nodal strengths associated with the attentional network were increased in the higher PA group suggest the preventive effects of PA on age-related cognitive decline, especially in attention.

  10. Osmosis in Cortical Collecting Tubules

    Science.gov (United States)

    Schafer, James A.; Troutman, Susan L.; Andreoli, Thomas E.

    1974-01-01

    The present experiments were designed to evaluate the effects of varying the osmolality of luminal solutions on the antidiuretic hormone (ADH)-independent water and solute permeability properties of isolated rabbit cortical collecting tubules. In the absence of ADH, the osmotic water permeability coefficient (cm s–1) Pfl→b, computed from volume flows from hypotonic lumen to isotonic bath, was 20 ± 4 x 10–4 (SEM); the value of Pfb→l in the absence of ADH, computed from volume flows from isotonic bath to hypertonic lumen, was 88 ± 15 x 10–4 cm s–1. We also measured apparent urea permeability coefficients (cm s–1) from 14C-urea fluxes from lumen to bath (P DDurea l→b) and from bath to lumen (P DDurea b→l). For hypotonic luminal solutions and isotonic bathing solutions, P DDurea l→b was 0.045 ± 0.004 x 10–4 and was unaffected by ADH. The ADH-independent values of P DDurea l→b and P urea b→l were, respectively, 0.216 ± 0.022 x 10–4 cm s–1 and 0.033 ± 0.002 x 10–4 cm s–1 for isotonic bathing solutions and luminal solutions made hypertonic with urea, i.e., there was an absolute increase in urea permeability and asymmetry of urea fluxes. Significantly, P DDurea l→b did not rise when luminal hypertonicity was produced by sucrose; and, bathing fluid hypertonicity did not alter tubular permeability to water or to urea. We interpret these data to indicate that luminal hypertonicity increased the leakiness of tight junctions to water and urea but not sucrose. Since the value of Pfb→l in the absence of ADH, when tight junctions were open to urea, was approximately half of the value of Pfl→b in the presence of ADH, when tight junctions were closed to urea, we conclude that tight junctions are negligible paracellular shunts for lumen to bath osmosis with ADH. These findings, together with those in the preceding paper, are discussed in terms of a solubility-diffusion model for water permeation in which ADH increases water solubility in

  11. Estimating immunoregulatory gene networks in human herpesvirus type 6-infected T cells

    International Nuclear Information System (INIS)

    Takaku, Tomoiku; Ohyashiki, Junko H.; Zhang, Yu; Ohyashiki, Kazuma

    2005-01-01

    The immune response to viral infection involves complex network of dynamic gene and protein interactions. We present here the dynamic gene network of the host immune response during human herpesvirus type 6 (HHV-6) infection in an adult T-cell leukemia cell line. Using a pathway-focused oligonucleotide DNA microarray, we found a possible association between chemokine genes regulating Th1/Th2 balance and genes regulating T-cell proliferation during HHV-6B infection. Gene network analysis using an integrated comprehensive workbench, VoyaGene, revealed that a gene encoding a TEC-family kinase, ITK, might be a putative modulator in the host immune response against HHV-6B infection. We conclude that Th2-dominated inflammatory reaction in host cells may play an important role in HHV-6B-infected T cells, thereby suggesting the possibility that ITK might be a therapeutic target in diseases related to dysregulation of Th1/Th2 balance. This study describes a novel approach to find genes related with the complex host-virus interaction using microarray data employing the Bayesian statistical framework

  12. An Environment IoT Sensor Network for Monitoring the Environment

    Science.gov (United States)

    Martinez, K.; Hart, J. K.; Bragg, O.; Black, A.; Bader, S.; Basford, P. J.; Bragg, G. M.; Fabre, A.

    2016-12-01

    The Internet of Things is a term which has emerged to describe the increase of Internet connectivity of everyday objects. While wireless sensor networks have developed highly energy efficient designs they need a step-change in their interoperability and usability to become more commonly used in Earth Science. IoT techniques can bring many of these advances while reusing some of the technologies developed for low power sensing. Here we concentrate on developing effective use of internet protocols throughout a low power sensor network. This includes 6LowPAN to provide a mesh IPv6 network, 40mW 868 MHz CC1120 radio transceivers to save power but provide kilometre range, a CC2538 ARM® Cortex®-M3 as main processor and CoAP to provide a binary HTTP-like interface to the nodes. We discuss in detail a system we deployed to monitor periglacial, peat and fluvial processes in the Scottish Highlands. The system linked initial nodes 3km away further up the mountain 2km away and used a CoAP GET sequence from a base station in the valley to gather the data. The IPv6 addressing and tunnelling allowed direct connectivity to desktops in Southampton. This provides insights into how the combination of low power techniques and emerging internet standards will bring advantages in interoperability, heterogeneity, usability and maintainability.

  13. The proximal straight tubule (PST) basolateral cell membrane water channel: selectivity characteristics.

    Science.gov (United States)

    Gutiérrez, A M; González, E; Echevarría, M; Hernández, C S; Whittembury, G

    1995-02-01

    Proximal straight tubules (PST) were dissected from rabbit kidneys, held by crimping pipettes in a chamber and bathed in a buffered isosmotic (295 mOsm/kg) solution containing 200 mM mannitol (MBS). Changes in tubule diameter were monitored on line with an inverted microscope, TV camera and image processor. The PST were then challenged for 20 sec with MBS made 35 mOsm/kg hyperosmotic by addition of either NaCl, KCl, mannitol (M), glycerol (G), ethylene glycol (E), glycine (g), urea (U), acetamide (A) or formamide (F). With NaCl, KCl, M, G, E, g, U, and A, tubules shrunk osmometrically within 0.5 sec and remained shrunk for as long as 20 sec without recovering their original volume (sometimes A showed some recovery). PST barely shrunk with F and quickly recovered their original volume. The permeability coefficients were 0 microns/sec (NaCl, M, g, E and U), 1 micron/sec (A), 84 microns/sec (F) and 0.02 micron/sec (G). The reflection coefficients sigma = 1.0 (NaCl, KCl, M, G, E, g and U), 0.95 (A) and 0.62 (F). Similar sigma values were obtained by substituting 200 mOsm/kg M in MBS by either NaCl, KCl, G, E, g, U, a or F. The olive oil/water partition coefficients are 5 (M), 15 (U), 85 (A) and 75 (F) (all x 10(-5)). Thus, part of F permeates the cell membrane through the lipid bilayer. The probing molecules van der Waals diameters are 7.4 x 8.2 x 12.0 (M), 3.6 x 5.2 x 5.4 (U), 3.8 x 5.2 x 5.4 (A) and (3.4 x 4.5 x 5.4 (F) A.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Objectives, Outlines, and Preparation for the Resist Tubule Space Experiment to Understand the Mechanism of Gravity Resistance in Plants

    Science.gov (United States)

    Hoson, Takayuki; Akamatsu, Haruhiko; Soga, Kouichi; Wakabayashi, Kazuyuki; Hashimoto, Hirofumi; Yamashita, Masamichi; Hasegawa, Katsuya; Yano, Sachiko; Omori, Katsunori; Ishioka, Noriaki; Matsumoto, Shohei; Kasahara, Haruo; Shimazu, Toru; A. Baba, Shoji; Hashimoto, Takashi

    Gravity resistance is a principal graviresponse in plants. In resistance to hypergravity, the gravity signal may be perceived by the mechanoreceptors located on the plasma membrane, and then transformed and transduced via the structural continuum or physiological continuity of cortical microtubules-plasma membrane-cell wall, leading to an increase in the cell wall rigidity as the final response. The Resist Tubule experiment, which will be conducted in the Kibo Module on the International Space Station, aims to confirm that this hypothesis is applicable to resistance to 1 G gravity. There are two major objectives in the Resist Tubule experiment. One is to quantify the contributions of cortical microtubules to gravity resistance using Arabidopsis tubulin mutants with different degrees of defects. Another objective is to analyze the modifications to dynamics of cortical microtubules and membrane rafts under microgravity conditions on-site by observing green fluorescent protein (GFP)-expressing Arabidopsis lines with the fluorescence microscope in the Kibo. We have selected suitable mutants, developed necessary hardware, and fixed operation procedure for the experiment.

  15. Specific non-monotonous interactions increase persistence of ecological networks.

    Science.gov (United States)

    Yan, Chuan; Zhang, Zhibin

    2014-03-22

    The relationship between stability and biodiversity has long been debated in ecology due to opposing empirical observations and theoretical predictions. Species interaction strength is often assumed to be monotonically related to population density, but the effects on stability of ecological networks of non-monotonous interactions that change signs have not been investigated previously. We demonstrate that for four kinds of non-monotonous interactions, shifting signs to negative or neutral interactions at high population density increases persistence (a measure of stability) of ecological networks, while for the other two kinds of non-monotonous interactions shifting signs to positive interactions at high population density decreases persistence of networks. Our results reveal a novel mechanism of network stabilization caused by specific non-monotonous interaction types through either increasing stable equilibrium points or reducing unstable equilibrium points (or both). These specific non-monotonous interactions may be important in maintaining stable and complex ecological networks, as well as other networks such as genes, neurons, the internet and human societies.

  16. Studying the evolutionary relationships and phylogenetic trees of 21 groups of tRNA sequences based on complex networks.

    Science.gov (United States)

    Wei, Fangping; Chen, Bowen

    2012-03-01

    To find out the evolutionary relationships among different tRNA sequences of 21 amino acids, 22 networks are constructed. One is constructed from whole tRNAs, and the other 21 networks are constructed from the tRNAs which carry the same amino acids. A new method is proposed such that the alignment scores of any two amino acids groups are determined by the average degree and the average clustering coefficient of their networks. The anticodon feature of isolated tRNA and the phylogenetic trees of 21 group networks are discussed. We find that some isolated tRNA sequences in 21 networks still connect with other tRNAs outside their group, which reflects the fact that those tRNAs might evolve by intercrossing among these 21 groups. We also find that most anticodons among the same cluster are only one base different in the same sites when S ≥ 70, and they stay in the same rank in the ladder of evolutionary relationships. Those observations seem to agree on that some tRNAs might mutate from the same ancestor sequences based on point mutation mechanisms.

  17. Comparative proteomic analysis of kidney distal convoluted tubule and cortical collecting duct cells following long-term hormonal stimulation

    DEFF Research Database (Denmark)

    Wu, Qi; Moller, Hanne; Rosenbaek, Lena Lindtoft

    2017-01-01

    The distal convoluted tubule (DCT) and the cortical collecting ducts (CCD) are portions of renal tubule that are partly responsible for maintaining the systemic concentrations of potassium, sodium, calcium and magnesium. Despite being structurally similar, DCT and CCD cells have different transpo...... FDR threshold in one cell type plus the unique proteins in this cell type. These 1025 mpkDCT specific proteins and 1211 mpkCCD specific proteins under the three conditions were subjected to further bioinformatics analyses including Panther and DAVID gene ontology analyses, E3 ligase...

  18. The sodium-bicarbonate cotransporter NBCe2 (slc4a5) expressed in human renal proximal tubules shows increased apical expression under high-salt conditions.

    Science.gov (United States)

    Gildea, John J; Xu, Peng; Carlson, Julia M; Gaglione, Robert T; Bigler Wang, Dora; Kemp, Brandon A; Reyes, Camellia M; McGrath, Helen E; Carey, Robert M; Jose, Pedro A; Felder, Robin A

    2015-12-01

    The electrogenic sodium bicarbonate cotransporter (NBCe2) is encoded by SLC4A5, variants of which have been associated with salt sensitivity of blood pressure, which affects 25% of the adult population. NBCe2 is thought to mediate sodium bicarbonate cotransport primarily in the renal collecting duct, but NBCe2 mRNA is also found in the rodent renal proximal tubule (RPT). The protein expression or function of NBCe2 has not been demonstrated in the human RPT. We validated an NBCe2 antibody by shRNA and Western blot analysis, as well as overexpression of an epitope-tagged NBCe2 construct in both RPT cells (RPTCs) and human embryonic kidney 293 (HEK293) cells. Using this validated NBCe2 antibody, we found NBCe2 protein expression in the RPT of fresh and frozen human kidney slices, RPTCs isolated from human urine, and isolated RPTC apical membrane. Under basal conditions, NBCe2 was primarily found in the Golgi, while NBCe1 was primarily found at the basolateral membrane. Following an acute short-term increase in intracellular sodium, NBCe2 expression was increased at the apical membrane in cultured slices of human kidney and polarized, immortalized RPTCs. Sodium bicarbonate transport was increased by monensin and overexpression of NBCe2, decreased by NBCe2 shRNA, but not by NBCe1 shRNA, and blocked by 2,2'-(1,2-ethenediyl)bis[5-isothiocyanato-benzenesulfonic acid]. NBCe2 could be important in apical sodium and bicarbonate cotransport under high-salt conditions; the implication of the ex vivo studies to the in vivo situation when salt intake is increased remains unclear. Therefore, future studies will examine the role of NBCe2 in mediating increased renal sodium transport in humans whose blood pressures are elevated by an increase in sodium intake. Copyright © 2015 the American Physiological Society.

  19. Comparative Evaluation of Efficacy of Iontophoresis with 0.33% Sodium Fluoride Gel and Diode Laser Alone on Occlusion of Dentinal Tubules.

    Science.gov (United States)

    Patil, Anup Raghunath; Varma, Siddhartha; Suragimath, Girish; Abbayya, Keshava; Zope, Sameer Anil; Kale, Vishwajeet

    2017-08-01

    Dentinal Hypersensitivity (DH) is one of the most commonly encountered clinical problems. Literature reveals no specific therapy to satisfactorily eliminate dentinal hypersensitivity. The aim of this study was to assess and compare the efficacy of iontophoresis with 0.33% Sodium Fluoride (NaF) gel and diode laser alone in dentinal tubule occlusion. This in vitro study included 20 teeth with intact root surfaces unaltered by extraction procedure for specimen preparation. Each tooth was cleaned, air dried and cut into three sections. Total 60 sections were prepared (30 longitudinal and 30 transverse sections), which were acid etched. In control group, no treatment was carried. In iontophoresis treatment group, samples were inserted into a foam tray containing 0.33 % NaF Gel and subjected to 1.5 mA output current for three minutes. In laser treatment group, specimens were lased with 980 nm diode laser at 0.5 W/PW (62.2J /cm 2 ) in a noncontact mode for 30 seconds. Specimens were evaluated under Scanning Electron Microscope (SEM) at 10KV to 20KV under x 2000, x5000 magnification for surface characteristics and patency of dentinal tubules. Total number of tubules visible, open, completely and partially occluded were recorded in each microphotograph and compared. On comparison, laser group showed the least number of open tubules i.e., 130 (31.1%) followed by iontophoresis group, 155 (51.32%) and control group 417 (100%). Diode laser application provided better results as compared to iontophoresis on occlusion of dentinal tubules. Hence, it can be used to treat the patients with DH.

  20. Subcellular trafficking of FGF controls tracheal invasion of Drosophila flight muscle.

    Science.gov (United States)

    Peterson, Soren J; Krasnow, Mark A

    2015-01-15

    To meet the extreme oxygen demand of insect flight muscle, tracheal (respiratory) tubes ramify not only on its surface, as in other tissues, but also within T-tubules and ultimately surrounding every mitochondrion. Although this remarkable physiological specialization has long been recognized, its cellular and molecular basis is unknown. Here, we show that Drosophila tracheoles invade flight muscle T-tubules through transient surface openings. Like other tracheal branching events, invasion requires the Branchless FGF pathway. However, localization of the FGF chemoattractant changes from all muscle membranes to T-tubules as invasion begins. Core regulators of epithelial basolateral membrane identity localize to T-tubules, and knockdown of AP-1γ, required for basolateral trafficking, redirects FGF from T-tubules to surface, increasing tracheal surface ramification and preventing invasion. We propose that tracheal invasion is controlled by an AP-1-dependent switch in FGF trafficking. Thus, subcellular targeting of a chemoattractant can direct outgrowth to specific domains, including inside the cell. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics

    NARCIS (Netherlands)

    Wilmes, Anja; Bielow, Chris; Ranninger, Christina; Bellwon, Patricia; Aschauer, Lydia; Limonciel, Alice; Chassaigne, Hubert; Kristl, Theresa; Aiche, Stephan; Huber, Christian G; Guillou, Claude; Hewitt, Philipp; Leonard, Martin O; Dekant, Wolfgang; Bois, Frederic Y; Jennings, Paul

    2015-01-01

    Cisplatin is one of the most widely used chemotherapeutic agents for the treatment of solid tumours. The major dose-limiting factor is nephrotoxicity, in particular in the proximal tubule. Here, we use an integrated omics approach, including transcriptomics, proteomics and metabolomics coupled to

  2. NMR-based urine analysis in rats: prediction of proximal tubule kidney toxicity and phospholipidosis.

    Science.gov (United States)

    Lienemann, Kai; Plötz, Thomas; Pestel, Sabine

    2008-01-01

    The aim of safety pharmacology is early detection of compound-induced side-effects. NMR-based urine analysis followed by multivariate data analysis (metabonomics) identifies efficiently differences between toxic and non-toxic compounds; but in most cases multiple administrations of the test compound are necessary. We tested the feasibility of detecting proximal tubule kidney toxicity and phospholipidosis with metabonomics techniques after single compound administration as an early safety pharmacology approach. Rats were treated orally, intravenously, inhalatively or intraperitoneally with different test compounds. Urine was collected at 0-8 h and 8-24 h after compound administration, and (1)H NMR-patterns were recorded from the samples. Variation of post-processing and feature extraction methods led to different views on the data. Support Vector Machines were trained on these different data sets and then aggregated as experts in an Ensemble. Finally, validity was monitored with a cross-validation study using a training, validation, and test data set. Proximal tubule kidney toxicity could be predicted with reasonable total classification accuracy (85%), specificity (88%) and sensitivity (78%). In comparison to alternative histological studies, results were obtained quicker, compound need was reduced, and very importantly fewer animals were needed. In contrast, the induction of phospholipidosis by the test compounds could not be predicted using NMR-based urine analysis or the previously published biomarker PAG. NMR-based urine analysis was shown to effectively predict proximal tubule kidney toxicity after single compound administration in rats. Thus, this experimental design allows early detection of toxicity risks with relatively low amounts of compound in a reasonably short period of time.

  3. Abnormal network flow detection based on application execution patterns from Web of Things (WoT) platforms.

    Science.gov (United States)

    Yoon, Young; Jung, Hyunwoo; Lee, Hana

    2018-01-01

    In this paper, we present a research work on a novel methodology of identifying abnormal behaviors at the underlying network monitor layer during runtime based on the execution patterns of Web of Things (WoT) applications. An execution pattern of a WoT application is a sequence of profiled time delays between the invocations of involved Web services, and it can be obtained from WoT platforms. We convert the execution pattern to a time sequence of network flows that are generated when the WoT applications are executed. We consider such time sequences as a whitelist. This whitelist reflects the valid application execution patterns. At the network monitor layer, our applied RETE algorithm examines whether any given runtime sequence of network flow instances does not conform to the whitelist. Through this approach, it is possible to interpret a sequence of network flows with regard to application logic. Given such contextual information, we believe that the administrators can detect and reason about any abnormal behaviors more effectively. Our empirical evaluation shows that our RETE-based algorithm outperforms the baseline algorithm in terms of memory usage.

  4. A Molecular Mechanism to Regulate Lysosome Motility for Lysosome Positioning and Tubulation

    Science.gov (United States)

    Li, Xinran; Rydzewski, Nicholas; Hider, Ahmad; Zhang, Xiaoli; Yang, Junsheng; Wang, Wuyang; Gao, Qiong; Cheng, Xiping; Xu, Haoxing

    2016-01-01

    To mediate the degradation of bio-macromolecules, lysosomes must traffic towards cargo-carrying vesicles for subsequent membrane fusion or fission. Mutations of the lysosomal Ca2+ channel TRPML1 cause lysosome storage disease (LSD) characterized by disordered lysosomal membrane trafficking in cells. Here we show that TRPML1 activity is required to promote Ca2+-dependent centripetal movement of lysosomes towards the perinuclear region, where autophagosomes accumulate, upon autophagy induction. ALG-2, an EF-hand-containing protein, serves as a lysosomal Ca2+ sensor that associates physically with the minus-end directed dynactin-dynein motor, while PI(3,5)P2, a lysosome-localized phosphoinositide, acts upstream of TRPML1. Furthermore, the PI(3,5)P2-TRPML1-ALG-2-dynein signaling is necessary for lysosome tubulation and reformation. In contrast, the TRPML1 pathway is not required for the perinuclear accumulation of lysosomes observed in many LSDs, which is instead likely caused by secondary cholesterol accumulation that constitutively activates Rab7-RILP-dependent retrograde transport. Collectively, Ca2+ release from lysosomes provides an on-demand mechanism regulating lysosome motility, positioning, and tubulation. PMID:26950892

  5. Proximal Tubules Have the Capacity to Regulate Uptake of Albumin.

    Science.gov (United States)

    Wagner, Mark C; Campos-Bilderback, Silvia B; Chowdhury, Mahboob; Flores, Brittany; Lai, Xianyin; Myslinski, Jered; Pandit, Sweekar; Sandoval, Ruben M; Wean, Sarah E; Wei, Yuan; Satlin, Lisa M; Wiggins, Roger C; Witzmann, Frank A; Molitoris, Bruce A

    2016-02-01

    Evidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level. Copyright © 2016 by the American Society of Nephrology.

  6. An Authentication and Key Management Mechanism for Resource Constrained Devices in IEEE 802.11-based IoT Access Networks

    Directory of Open Access Journals (Sweden)

    Ki-Wook Kim

    2017-09-01

    Full Text Available Many Internet of Things (IoT services utilize an IoT access network to connect small devices with remote servers. They can share an access network with standard communication technology, such as IEEE 802.11ah. However, an authentication and key management (AKM mechanism for resource constrained IoT devices using IEEE 802.11ah has not been proposed as yet. We therefore propose a new AKM mechanism for an IoT access network, which is based on IEEE 802.11 key management with the IEEE 802.1X authentication mechanism. The proposed AKM mechanism does not require any pre-configured security information between the access network domain and the IoT service domain. It considers the resource constraints of IoT devices, allowing IoT devices to delegate the burden of AKM processes to a powerful agent. The agent has sufficient power to support various authentication methods for the access point, and it performs cryptographic functions for the IoT devices. Performance analysis shows that the proposed mechanism greatly reduces computation costs, network costs, and memory usage of the resource-constrained IoT device as compared to the existing IEEE 802.11 Key Management with the IEEE 802.1X authentication mechanism.

  7. An Authentication and Key Management Mechanism for Resource Constrained Devices in IEEE 802.11-based IoT Access Networks.

    Science.gov (United States)

    Kim, Ki-Wook; Han, Youn-Hee; Min, Sung-Gi

    2017-09-21

    Many Internet of Things (IoT) services utilize an IoT access network to connect small devices with remote servers. They can share an access network with standard communication technology, such as IEEE 802.11ah. However, an authentication and key management (AKM) mechanism for resource constrained IoT devices using IEEE 802.11ah has not been proposed as yet. We therefore propose a new AKM mechanism for an IoT access network, which is based on IEEE 802.11 key management with the IEEE 802.1X authentication mechanism. The proposed AKM mechanism does not require any pre-configured security information between the access network domain and the IoT service domain. It considers the resource constraints of IoT devices, allowing IoT devices to delegate the burden of AKM processes to a powerful agent. The agent has sufficient power to support various authentication methods for the access point, and it performs cryptographic functions for the IoT devices. Performance analysis shows that the proposed mechanism greatly reduces computation costs, network costs, and memory usage of the resource-constrained IoT device as compared to the existing IEEE 802.11 Key Management with the IEEE 802.1X authentication mechanism.

  8. Proximal tubule Na transporter responses are the same during acute and chronic hypertension

    DEFF Research Database (Denmark)

    Magyar, C E; Zhang, Y; Holstein-Rathlou, N H

    2000-01-01

    Acute hypertension in Sprague-Dawley rats (SD) provokes a decrease in renal proximal tubule (PT) salt and fluid reabsorption, redistribution of apical Na/H exchanger isoform 3 (NHE3) and Na-P(i) cotransporter type 2 (NaPi2) out of the brush border into higher density membranes, and inhibition...... to persistent adaptive changes in NHE3 and NaPi2 distribution and/or NKA activity. Renal cortex Na transporter protein density distributions and activities were compared by subcellular fractionation in 1) adult SHR with an acute increase or decrease in arterial pressure and 2) young SD (YSD) and young SHR (YSHR......) vs. adult SD and SHR. In adult hypertensive SHR NHE3 was shifted to membranes of higher densities, analogous to SD with acute hypertension, and there were no further changes with a further increase or decrease in arterial pressure. There was no change in total pool size of NHE3 in cortex in YSHR vs...

  9. Reconstruction of mouse testicular cellular microenvironments in long-term seminiferous tubule culture.

    Directory of Open Access Journals (Sweden)

    Juho-Antti Mäkelä

    Full Text Available Research on spermatogonia is hampered by complex architecture of the seminiferous tubule, poor viability of testicular tissue ex vivo and lack of physiologically relevant long-term culture systems. Therefore there is a need for an in vitro model that would enable long term survival and propagation of spermatogonia. We aimed at the most simplified approach to enable all different cell types within the seminiferous tubules to contribute to the creation of a niche for spermatogonia. In the present study we describe the establishment of a co-culture of mouse testicular cells that is based on proliferative and migratory activity of seminiferous tubule cells and does not involve separation, purification or differential plating of individual cell populations. The co-culture is composed of the constituents of testicular stem cell niche: Sertoli cells [identified by expression of Wilm's tumour antigen 1 (WT1 and secretion of glial cell line-derived neurotrophic factor, GDNF], peritubular myoid cells (expressing alpha smooth muscle actin, αSMA and spermatogonia [expressing MAGE-B4, PLZF (promyelocytic leukaemia zinc finger, LIN28, Gpr125 (G protein-coupled receptor 125, CD9, c-Kit and Nanog], and can be maintained for at least five weeks. GDNF was found in the medium at a sufficient concentration to support proliferating spermatogonial stem cells (SSCs that were able to start spermatogenic differentiation after transplantation to an experimentally sterile recipient testis. Gdnf mRNA levels were elevated by follicle-stimulating hormone (FSH which shows that the Sertoli cells in the co-culture respond to physiological stimuli. After approximately 2-4 weeks of culture a spontaneous formation of cord-like structures was monitored. These structures can be more than 10 mm in length and branch. They are formed by peritubular myoid cells, Sertoli cells, fibroblasts and spermatogonia as assessed by gene expression profiling. In conclusion, we have managed to

  10. The effect of L-cysteine on the portion-selective uptake of cadmium in the renal proximal tubule

    International Nuclear Information System (INIS)

    Murakami, Masataka; Sano, Kenichi; Webb, M.

    1987-01-01

    Cadmium (Cd), co-administered with an excess of L-cysteine, accumulates rapidly in the kidneys of the rat. After subcutaneous (s.c.) injection of 3 μmol CdCl 2 /kg body wt the concentrations of Cd in the blood and kidneys increase with the dose of cysteine over the range 0.06-5.0 mmol/kg body wt. At cysteine doses of less than 1.5 mmol/kg body wt the ratio of the concentrations of Cd in the outer medulla and cortex of the kidney remains the same as that after the injection of Cd alone. This ratio, however, is more than doubled at dose levels of 5-10 mmol cysteine/kg body wt. Hepatic uptake of Cd is unaffected by doses of cysteine below 1.5 mmol/kg body wt but decreases markedly at higher doses. In animals that are dosed simultaneously with 5 mmol cysteine/kg body wt, renal uptake of 109 Cd is known to occur in the straight segments of the proximal tubules. At a dose level of less than 1.5 mmol cysteine/kg body wt the present autoradiographical studies show that 109 Cd is taken up predominantly by the proximal convoluted tubules of the kidney cortex. At the critical dose level (1.5 mmol/kg body wt), cysteine decreases the retention of Cd at the s.c. injection site, but probably has little effect on the distribution of Cd between protein and other carrier molecules in the blood. This distribution, however, is altered at higher cysteine dose levels. It is suggested that, under the latter conditions, stable Cd-cysteine complexes are formed in the blood and are filtered readily through the glomeruli. These complexes are taken up in the kidney at the sites of cysteine reabsorption which, by studies with L-[ 35 S]-cysteine, are identified as the straight segments of the proximal tubules. (orig.)

  11. In vitro remineralization of enamel subsurface lesions and assessment of dentine tubule occlusion from NaF dentifrices with and without calcium

    Directory of Open Access Journals (Sweden)

    A R Prabhakar

    2013-01-01

    Full Text Available Currently, fluoride is the most effective preventive treatment for remineralization of incipient carious lesions and dentinal hypersensitivity due to wasting disorders. The products containing fluoride, calcium and phosphate are also claim to remineralize early, non-cavitated enamel demineralization. The aim of this study was to investigate and compare the efficacy of two such products, Tooth Mousse and Clinpro tooth crème on remineralization and tubule occluding ability with 5000ppm fluoride-containing toothpaste. Materials and Methods :Thirty third molar teeth were placed in demineralizing solution for 5 days such that only a window of 1mm x 5mm was exposed to the environment to produce artificial caries-like lesions and randomly assigned to three groups: Group I, 5000ppm sodium fluoride; Group II, GC MI paste plus and Group III, Clinpro tooth crème. Axial longitudinal sections of 140-160 μm of each tooth which included the artificial carious lesion taken and were photographed under polarized light microscope. The demineralized areas were then quantified with a computerized imaging system. The experimental materials were applied onto the tooth sections as a topical coating and subjected to pH-cycling for 28 days. To evaluate tubule occlusion ability, thirty dentin specimens of 2mm thickness were obtained from cervical third of sound third molars. Specimens were ultrasonicated and etched with 6% citric acid for 2 minutes to simulate the hypersensitive dentin. Specimens were randomly divided into above mentioned three groups (n=10. The test agents were brushed over the specimens with an electric toothbrush, prepared and observed under Scanning Electron Microscope for calculation of the percentage of occluded tubules. Results: Group I showed a significantly greater percentage of remineralization than Group III and Group II. Comparison of the remineralization potential between group II and group III were not significant.In case of dentine

  12. Photoelectrochemical reactivity of polyoxophosphotungstates embedded in titania tubules

    International Nuclear Information System (INIS)

    Xie Yibing

    2006-01-01

    A highly ordered and crystallized titania (TiO 2 ) nanotube array is fabricated by a low-voltage anodization plus a post-embedding calcination process. Polyoxophosphotungstate-titania (POPTA-TiO 2 ) composite catalyst is synthesized by embedding POPTA in TiO 2 tubule channels to improve the photoelectrochemical properties. The morphological characteristics and crystal behaviour of POPTA-TiO 2 are examined by field-emission scanning electron microscopy and x-ray diffraction. The stability of the chemical structure has been analysed by Fourier transformed infrared spectroscopy measurements. The photoelectrochemical properties are investigated by means of the polarization current response. Photocatalytic and photoelectrocatalytic reactivities for the degradation of an endocrine disrupting chemical have also been investigated to examine the photoelectrochemical reaction efficiency of POPTA-TiO 2 composite catalyst

  13. An Authentication and Key Management Mechanism for Resource Constrained Devices in IEEE 802.11-based IoT Access Networks

    OpenAIRE

    Kim, Ki-Wook; Han, Youn-Hee; Min, Sung-Gi

    2017-01-01

    Many Internet of Things (IoT) services utilize an IoT access network to connect small devices with remote servers. They can share an access network with standard communication technology, such as IEEE 802.11ah. However, an authentication and key management (AKM) mechanism for resource constrained IoT devices using IEEE 802.11ah has not been proposed as yet. We therefore propose a new AKM mechanism for an IoT access network, which is based on IEEE 802.11 key management with the IEEE 802.1X aut...

  14. Elucidation of density profile of self-assembled sitosterol + oryzanol tubules with small-angle neutron scattering

    NARCIS (Netherlands)

    Bot, A.; Gilbert, E.P.; Bouwman, W.G.; Sawalha, H.I.M.; Adel, den R.; Garamus, V.M.; Venema, P.; Linden, van der E.; Flöter, E.

    2012-01-01

    Small-angle neutron scattering (SANS) experiments have been performed on self-assembled tubules of sitosterol and oryzanol in triglyceride oils to investigate details of their structure. Alternative organic phases (deuterated and non-deuterated decane, limonene, castor oil and eugenol) were used to

  15. Efficacy of 4 Irrigation Protocols in Killing Bacteria Colonized in Dentinal Tubules Examined by a Novel Confocal Laser Scanning Microscope Analysis.

    Science.gov (United States)

    Azim, Adham A; Aksel, Hacer; Zhuang, Tingting; Mashtare, Terry; Babu, Jegdish P; Huang, George T-J

    2016-06-01

    The aim of this study was to determine the efficiency of 4 irrigation systems in eliminating bacteria in root canals, particularly in dentinal tubules. Roots of human teeth were prepared to 25/04, autoclaved, and inoculated with Enterococcus faecalis for 3 weeks. Canals were then disinfected by (1) standard needle irrigation, (2) sonically agitating with EndoActivator, (3) XP Endo finisher, or (4) erbium:yttrium aluminum garnet laser (PIPS) (15 roots/group). The bacterial reduction in the canal was determined by MTT assays. For measuring live versus dead bacteria in the dentinal tubules (4 teeth/group), teeth were split open and stained with LIVE/DEAD BackLight. Coronal, middle, and apical thirds of the canal dentin were scanned by using a confocal laser scanning microscope (CLSM) to determine the ratio of dead/total bacteria in the dentinal tubules at various depths. All 4 irrigation protocols significantly eliminated bacteria in the canal, ranging from 89.6% to 98.2% reduction (P bacteria in the coronal, middle, and apical segments at 50-μm depth. On the other hand, PIPS had the greatest bacterial killing efficiency at the 150-μm depth in all 3 root segments. XP Endo appears to be more efficient than other 3 techniques in disinfecting the main canal space and up to 50 μm deep into the dentinal tubules. PIPS appears to be most effective in killing the bacteria deep in the dentinal tubules. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  16. CoNekT: an open-source framework for comparative genomic and transcriptomic network analyses.

    Science.gov (United States)

    Proost, Sebastian; Mutwil, Marek

    2018-05-01

    The recent accumulation of gene expression data in the form of RNA sequencing creates unprecedented opportunities to study gene regulation and function. Furthermore, comparative analysis of the expression data from multiple species can elucidate which functional gene modules are conserved across species, allowing the study of the evolution of these modules. However, performing such comparative analyses on raw data is not feasible for many biologists. Here, we present CoNekT (Co-expression Network Toolkit), an open source web server, that contains user-friendly tools and interactive visualizations for comparative analyses of gene expression data and co-expression networks. These tools allow analysis and cross-species comparison of (i) gene expression profiles; (ii) co-expression networks; (iii) co-expressed clusters involved in specific biological processes; (iv) tissue-specific gene expression; and (v) expression profiles of gene families. To demonstrate these features, we constructed CoNekT-Plants for green alga, seed plants and flowering plants (Picea abies, Chlamydomonas reinhardtii, Vitis vinifera, Arabidopsis thaliana, Oryza sativa, Zea mays and Solanum lycopersicum) and thus provide a web-tool with the broadest available collection of plant phyla. CoNekT-Plants is freely available from http://conekt.plant.tools, while the CoNekT source code and documentation can be found at https://github.molgen.mpg.de/proost/CoNekT/.

  17. Proximal tubule proteins are significantly elevated in bladder urine of patients with ureteropelvic junction obstruction and may represent novel biomarkers: A pilot study.

    Science.gov (United States)

    Gerber, Claire; Harel, Miriam; Lynch, Miranda L; Herbst, Katherine W; Ferrer, Fernando A; Shapiro, Linda H

    2016-04-01

    Ureteropelvic junction obstruction (UPJO) is the major cause of hydronephrosis in children and may lead to renal injury and early renal dysfunction. However, diagnosis of the degree of obstruction and severity of renal injury relies on invasive and often inconclusive renal scans. Biomarkers from voided urine that detect early renal injury are highly desirable because of their noninvasive collection and their potential to assist in earlier and more reliable diagnosis of the severity of obstruction. Early in response to UPJO, increased intrarenal pressure directly impacts the proximal tubule brush border. We hypothesize that single-pass, apically expressed proximal tubule brush border proteins will be shed into the urine early and rapidly and will be reliable noninvasive urinary biomarkers, providing the tools for a more reliable stratification of UPJO patients. We performed a prospective cohort study at Connecticut Children's Medical Center. Bladder urine samples from 12 UPJO patients were obtained prior to surgical intervention. Control urine samples were collected from healthy pediatric patients presenting with primary nocturnal enuresis. We determined levels of NGAL, KIM-1 (previously identified biomarkers), CD10, CD13, and CD26 (potentially novel biomarkers) by ELISA in control and experimental urine samples. Urinary creatinine levels were used to normalize the urinary protein levels measured by ELISA. Each of the proximal tubule proteins outperformed the previously published biomarkers. No differences in urinary NGAL and KIM-1 levels were observed between control and obstructed patients (p = 0.932 and p = 0.799, respectively). However, levels of CD10, CD13, and CD26 were significantly higher in the voided urine of obstructed individuals when compared with controls (p = 0.002, p = 0.024, and p = 0.007, respectively) (Figure). Targeted identification of reliable, noninvasive biomarkers of renal injury is critical to aid in diagnosing patients at risk, guiding

  18. The role of renal proximal tubule P450 enzymes in chloroform-induced nephrotoxicity: Utility of renal specific P450 reductase knockout mouse models

    International Nuclear Information System (INIS)

    Liu, Senyan; Yao, Yunyi; Lu, Shijun; Aldous, Kenneth; Ding, Xinxin; Mei, Changlin; Gu, Jun

    2013-01-01

    The kidney is a primary target for numerous toxic compounds. Cytochrome P450 enzymes (P450) are responsible for the metabolic activation of various chemical compounds, and in the kidney are predominantly expressed in proximal tubules. The aim of this study was to test the hypothesis that renal proximal tubular P450s are critical for nephrotoxicity caused by chemicals such as chloroform. We developed two new mouse models, one having proximal tubule-specific deletion of the cytochrome P450 reductase (Cpr) gene (the enzyme required for all microsomal P450 activities), designated proximal tubule-Cpr-null (PTCN), and the other having proximal tubule-specific rescue of CPR activity with the global suppression of CPR activity in all extra-proximal tubular tissues, designated extra-proximal tubule-Cpr-low (XPT-CL). The PTCN, XPT-CL, Cpr-low (CL), and wild-type (WT) mice were treated with a single oral dose of chloroform at 200 mg/kg. Blood, liver and kidney samples were obtained at 24 h after the treatment. Renal toxicity was assessed by measuring BUN and creatinine levels, and by pathological examination. The blood and tissue levels of chloroform were determined. The severity of toxicity was less in PTCN and CL mice, compared with that of WT and XPT-CL mice. There were no significant differences in chloroform levels in the blood, liver, or kidney, between PTCN and WT mice, or between XPT-CL and CL mice. These findings indicate that local P450-dependent activities play an important role in the nephrotoxicity induced by chloroform. Our results also demonstrate the usefulness of these novel mouse models for studies of chemical-induced kidney toxicity. - Highlights: • New mouse models were developed with varying P450 activities in the proximal tubule. • These mouse models were treated with chloroform, a nephrotoxicant. • Studies showed the importance of local P450s in chloroform-induced nephrotoxicity

  19. Renal compensation to chronic hypoxic hypercapnia: downregulation of pendrin and adaptation of the proximal tubule.

    NARCIS (Netherlands)

    Seigneux, S. de; Malte, H.; Dimke, H.; Frokiaer, J.; Nielsen, S.; Frische, S.

    2007-01-01

    The molecular basis for the renal compensation to respiratory acidosis and specifically the role of pendrin in this condition are unclear. Therefore, we studied the adaptation of the proximal tubule and the collecting duct to respiratory acidosis. Male Wistar-Hannover rats were exposed to either

  20. Network topology of olivine-basalt partial melts

    Science.gov (United States)

    Skemer, Philip; Chaney, Molly M.; Emmerich, Adrienne L.; Miller, Kevin J.; Zhu, Wen-lu

    2017-07-01

    The microstructural relationship between melt and solid grains in partially molten rocks influences many physical properties, including permeability, rheology, electrical conductivity and seismic wave speeds. In this study, the connectivity of melt networks in the olivine-basalt system is explored using a systematic survey of 3-D X-ray microtomographic data. Experimentally synthesized samples with 2 and 5 vol.% melt are analysed as a series of melt tubules intersecting at nodes. Each node is characterized by a coordination number (CN), which is the number of melt tubules that intersect at that location. Statistically representative volumes are described by coordination number distributions (CND). Polyhedral grains can be packed in many configurations yielding different CNDs, however widely accepted theory predicts that systems with small dihedral angles, such as olivine-basalt, should exhibit a predominant CN of four. In this study, melt objects are identified with CN = 2-8, however more than 50 per cent are CN = 4, providing experimental verification of this theoretical prediction. A conceptual model that considers the role of heterogeneity in local grain size and melt fraction is proposed to explain the formation of nodes with CN ≠ 4. Correctly identifying the melt network topology is essential to understanding the relationship between permeability and porosity, and hence the transport properties of partial molten mantle rocks.

  1. Inhibition delay increases neural network capacity through Stirling transform

    Science.gov (United States)

    Nogaret, Alain; King, Alastair

    2018-03-01

    Inhibitory neural networks are found to encode high volumes of information through delayed inhibition. We show that inhibition delay increases storage capacity through a Stirling transform of the minimum capacity which stabilizes locally coherent oscillations. We obtain both the exact and asymptotic formulas for the total number of dynamic attractors. Our results predict a (ln2) -N-fold increase in capacity for an N -neuron network and demonstrate high-density associative memories which host a maximum number of oscillations in analog neural devices.

  2. Effect of dental materials on gluconeogenesis in rat kidney tubules

    Energy Technology Data Exchange (ETDEWEB)

    Reichl, F.X.; Durner, J.; Mueckter, H.; Elsenhans, B.; Forth, W. [Muenchen Univ. (Germany). Walter-Straub-Institut fuer Pharmakologie und Toxikologie; Kunzelmann, K.H.; Hickel, R. [Department of Operative/Restorative Dentistry, Periodontology and Pedodontics, Ludwig-Maximilians-University of Munich (Germany); Spahl, W. [Institute of Organic Chemistry, Ludwig-Maximilians-University of Munich (Germany); Hume, W.R. [Dental Research Institute, Univ. of California, Los Angeles, CA (United States); Moes, G.W. [TNO Prins-Maurits-Laboratorium, Rijswijk (Netherlands)

    1999-09-01

    The effect of dental composite components triethyleneglycoldimethacrylate (TEGDMA) and hydroxyethylmethacrylate (HEMA) as well as mercuric chloride (HgCl{sub 2}) and methylmercury chloride (MeHgCl) on gluconeogenesis was investigated in isolated rat kidney tubules. From starved rats kidney tubules were prepared and isolated by digestion with collagenase. Every 10 min up to 60 min 1-ml samples were drawn from the cell suspension for quantitating the glucose content. Glucose formation in controls was 3.3 {+-} 0.2 nmol/mg . per min (mean {+-} SEM, n=21). Relative rates of glucose formation were obtained by expressing individual rates as a percentage of the corresponding control. X-Y concentration curves (effective concentration, EC) of the substances were calculated by fitting a four-parametric sigmoid function to the relative rates of glucose formation at various test concentrations. At the end of the incubation period cell viability was assessed by trypan blue exclusion. Cell viability decreased within the 60 min interval from 90 to approx. 80% (controls), <25 (HEMA), <20 (TEGDMA), <10 (MeHgCl), and <10% (HgCl{sub 2}). Values of 50% effective concentration (EC{sub 50}) were calculated from fitted curves. EC{sub 50} values were (mmol; mean {+-} SEM; n=4): HEMA, 17.7 {+-} 2.9; TEGDMA, 1.8 {+-} 0.2; MeHgCl, 0.018 {+-} 0.0005; and HgCl{sub 2}, 0.0016 {+-} 0.0005. The toxic effect of HgCl{sub 2} was {proportional{underscore}to}1000 or 10 000 higher than that of the dental composite components TEGDMA or HEMA, respectively. (orig.)

  3. Fabrication of Collagen Gel Hollow Fibers by Covalent Cross-Linking for Construction of Bioengineering Renal Tubules.

    Science.gov (United States)

    Shen, Chong; Zhang, Guoliang; Wang, Qichen; Meng, Qin

    2015-09-09

    Collagen, the most used natural biomacromolecule, has been extensively utilized to make scaffolds for cell cultures in tissue engineering, but has never been fabricated into the configuration of a hollow fiber (HF) for cell culture due to its poor mechanical properties. In this study, renal tubular cell-laden collagen hollow fiber (Col HF) was fabricated by dissolving sacrificial Ca-alginate cores from collagen shells strengthened by carbodiimide cross-linking. The inner/outer diameters of the Col HF were precisely controlled by the flow rates of core alginate/shell collagen solution in the microfluidic device. As found, the renal tubular cells self-assembled into renal tubules with diameters of 50-200 μm post to the culture in Col HF for 10 days. According to the 3D reconstructed confocal images or HE staining, the renal cells appeared as a tight tubular monolayer on the Col HF inner surface, sustaining more 3D cell morphology than the cell layer on the 2D flat collagen gel surface. Moreover, compared with the cultures in either a Transwell or polymer HF membrane, the renal tubules in Col HF exhibited at least 1-fold higher activity on brush border enzymes of alkaline phosphatase and γ-glutamyltransferase, consistent with their gene expressions. The enhancement occurred similarly on multidrug resistance protein 2 and glucose uptake. Such bioengineered renal tubules in Col HF will present great potential as alternatives to synthetic HF in both clinical use and pharmaceutical investigation.

  4. A Smart and Balanced Energy-Efficient Multihop Clustering Algorithm (Smart-BEEM) for MIMO IoT Systems in Future Networks.

    Science.gov (United States)

    Xu, Lina; O'Hare, Gregory M P; Collier, Rem

    2017-07-05

    Wireless Sensor Networks (WSNs) are typically composed of thousands of sensors powered by limited energy resources. Clustering techniques were introduced to prolong network longevity offering the promise of green computing. However, most existing work fails to consider the network coverage when evaluating the lifetime of a network. We believe that balancing the energy consumption in per unit area rather than on each single sensor can provide better-balanced power usage throughout the network. Our former work-Balanced Energy-Efficiency (BEE) and its Multihop version BEEM can not only extend the network longevity, but also maintain the network coverage. Following WSNs, Internet of Things (IoT) technology has been proposed with higher degree of diversities in terms of communication abilities and user scenarios, supporting a large range of real world applications. The IoT devices are embedded with multiple communication interfaces, normally referred as Multiple-In and Multiple-Out (MIMO) in 5G networks. The applications running on those devices can generate various types of data. Every interface has its own characteristics, which may be preferred and beneficial in some specific user scenarios. With MIMO becoming more available on the IoT devices, an advanced clustering solution for highly dynamic IoT systems is missing and also pressingly demanded in order to cater for differing user applications. In this paper, we present a smart clustering algorithm (Smart-BEEM) based on our former work BEE(M) to accomplish energy efficient and Quality of user Experience (QoE) supported communication in cluster based IoT networks. It is a user behaviour and context aware approach, aiming to facilitate IoT devices to choose beneficial communication interfaces and cluster headers for data transmission. Experimental results have proved that Smart-BEEM can further improve the performance of BEE and BEEM for coverage sensitive longevity.

  5. ON OPERATION OF 740 M LONG FREIGHT TRAINS ON CZECH TEN-T RAILWAY NETWORK

    Directory of Open Access Journals (Sweden)

    Michal Drábek

    2016-09-01

    Full Text Available Regulation (EU No 1315/2013 defines actual scope of core and comprehensive TEN-T network, including both networks for railway freight transport. For the core network, possibility to operate 740 m long freight trains is required. The aim of this paper is to analyse availability of appropriate overtaking tracks for 740 m long freight trains. Due to ETCS braking curves and odometry, such trains, after ETCS implementation, will require 780-800 m long overtaking tracks. For practical reasons (e.g. bypass lines, whole Czech railway TEN-T network is analysed. The overtaking track, whose occupation means influence on scheduled traffic or threat to boarding passengers, are excluded. The data was collected from station schemes from Collection of Official Requisites for 2015/16 Timetable, issued by SŽDC, Czech state Infrastructure Manager. Most of appropriate tracks are over 800 m long, but their density in the network and in particular directions varies considerably. For freight traffic, gradient of the line is important, so in the resulting figure, there are marked significant peaks for particular lines as well. Czech TEN-T lines are further segmented on the basis of number of tracks and their traffic character. Then, specific issues on overtaking or crossing of 740 m long freight trains are discussed. As a conclusion, for long-term development of Czech TEN-T lines, targeted investment is recommended not only for passenger railway, but also for freight railway. An attractive capacity offer for railway undertakings, which can stimulate freight traffic on European Rail freight corridors, can be represented by network-bound periodic freight train paths with suitable long overtaking tracks outside bottlenecks. After the overtaking by passenger trains, a freight train should run without stop through large node station or a bottleneck area. Before the sections with high gradients, coupling of additional locomotives should be connected with the overtaking

  6. Association between structural brain network efficiency and intelligence increases during adolescence

    NARCIS (Netherlands)

    Koenis, Marinka M G; Brouwer, Rachel M; Swagerman, Suzanne C; van Soelen, Inge L C; Boomsma, Dorret I; Hulshoff Pol, Hilleke E

    2018-01-01

    Adolescence represents an important period during which considerable changes in the brain take place, including increases in integrity of white matter bundles, and increasing efficiency of the structural brain network. A more efficient structural brain network has been associated with higher

  7. Leveraging BLE and LoRa in IoT Network for Wildlife Monitoring System (WMS)

    NARCIS (Netherlands)

    Ayele, Eyuel Debebe; Das, Kallol; Meratnia, Nirvana; Havinga, Paul J.M.

    2018-01-01

    In this paper we propose a new dual radio IoT network architecture for wildlife monitoring system (WMS). WMS leverages bluetooth low energy (BLE) in low power wide area networks (LPWANs) by dynamically changing the operating radio based on the proximity among herd of wild animals. This approach will

  8. Leveraging BLE and LoRa in IoT Network for Wildlife Monitoring System (WMS)

    NARCIS (Netherlands)

    Ayele, Eyuel Debebe; Das, Kallol; Meratnia, Nirvana; Havinga, Paul J.M.

    2016-01-01

    In this paper we propose a new dual radio IoT network architecture for wildlife monitoring system (WMS). WMS leverages bluetooth low energy (BLE) in low power wide area networks (LPWANs) by dynamically changing the operating radio based on the proximity among herd of wild animals. This approach will

  9. Increased thyroidal T4 to T3 conversion in autonomously functioning thyroid adenoma: from euthyroidism to thyrotoxicosis.

    LENUS (Irish Health Repository)

    Solter, M

    2012-01-31

    AIM: The aim was to investigate whether the intrathyroid conversion of T4 to T3 in autonomously functioning thyroid adenoma (AFTA) tissue could influence serum T3 levels and suppression of TSH, especially in patients with borderline thyroid function. PATIENTS AND METHODS: In ten patients with AFTA, thyroidal conversion of T4 to T3 was investigated in nodular and paranodular, TSH-suppressed tissue. All patients had normal serum T4 and suppressed TSH. Serum T3 was normal in six, and borderline or slightly increased in four. AFTA and paranodular tissues were surgically removed and frozen at -70 degrees C, then homogenized in a glass homogenizer, centrifuged at 100,000xg, and particulate fraction collected as a pellet. Analysis mixture consisted of thyroid enzyme suspension in 50 mumol\\/L TRIS buffer with 5 mumol DTT and 200 muL 1.3 mumol T4. Incubation was performed at 37 degrees C and the generation of T3 measured after 5, 10, 20 and 40 minutes respectively. RESULTS: T3 production (pmol\\/mg protein) was significantly higher in AFTA than in paranodular tissues (8.8 1.2\\/Mean +\\/- SE\\/vs. 1.8 +\\/- 0.2; p<0.01), and excessively high (9.8, 14.1, 14.2 and 15.0) in four patients with borderline or slightly supranormal serum T3. A significant correlation was found between serum T3 concentrations and T3 generation (T4 conversion) in AFTA tissues. CONCLUSION: Results suggest that increased thyroidal T4 to T3 conversion in AFTA tissue could be involved in an increased delivery of T3, increased serum T3 and suppressed serum TSH, particularly in patients with the disease evolving from euthyroid to an early hyperthyroid phase.

  10. P-glycoprotein-deficient mice have proximal tubule dysfunction but are protected against ischemic renal injury

    NARCIS (Netherlands)

    Huls, M.; Kramers, C.; Levtchenko, E.N.; Wilmer, M.J.G.; Dijkman, H.B.P.M.; Kluijtmans, L.A.J.; Hoorn, J.W.A. van der; Russel, F.G.M.; Masereeuw, R.

    2007-01-01

    The multidrug resistance gene 1 product, P-glycoprotein (P-gp), is expressed in several excretory organs, including the apical membrane of proximal tubules. After inducing acute renal failure, P-gp expression is upregulated and this might be a protective function by pumping out toxicants and harmful

  11. Thiazolidinediones enhance sodium-coupled bicarbonate absorption from renal proximal tubules via PPARγ-dependent nongenomic signaling.

    Science.gov (United States)

    Endo, Yoko; Suzuki, Masashi; Yamada, Hideomi; Horita, Shoko; Kunimi, Motoei; Yamazaki, Osamu; Shirai, Ayumi; Nakamura, Motonobu; Iso-O, Naoyuki; Li, Yuehong; Hara, Masumi; Tsukamoto, Kazuhisa; Moriyama, Nobuo; Kudo, Akihiko; Kawakami, Hayato; Yamauchi, Toshimasa; Kubota, Naoto; Kadowaki, Takashi; Kume, Haruki; Enomoto, Yutaka; Homma, Yukio; Seki, George; Fujita, Toshiro

    2011-05-04

    Thiazolidinediones (TZDs) improve insulin resistance by activating a nuclear hormone receptor, peroxisome proliferator-activated receptor γ (PPARγ). However, the use of TZDs is associated with plasma volume expansion through a mechanism that remains to be clarified. Here we showed that TZDs rapidly stimulate sodium-coupled bicarbonate absorption from the renal proximal tubule in vitro and in vivo. TZD-induced transport stimulation is dependent on PPARγ-Src-EGFR-ERK and observed in rat, rabbit and human, but not in mouse proximal tubules where Src-EGFR is constitutively activated. The existence of PPARγ-Src-dependent nongenomic signaling, which requires the ligand-binding ability, but not the transcriptional activity of PPARγ, is confirmed in mouse embryonic fibroblast cells. The enhancement of the association between PPARγ and Src by TZDs supports an indispensable role of Src in this signaling. These results suggest that the PPARγ-dependent nongenomic stimulation of renal proximal transport is also involved in TZD-induced volume expansion. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Update on Mechanisms of Renal Tubule Injury Caused by Advanced Glycation End Products

    Directory of Open Access Journals (Sweden)

    Hong Sun

    2016-01-01

    Full Text Available Diabetic nephropathy (DN caused by advanced glycation end products (AGEs may be associated with lipid accumulation in the kidneys. This study was designed to investigate whether Nε-(carboxymethyl lysine (CML, a member of the AGEs family increases lipid accumulation in a human renal tubular epithelial cell line (HK-2 via increasing cholesterol synthesis and uptake and reducing cholesterol efflux through endoplasmic reticulum stress (ERS. Our results showed that CML disrupts cholesterol metabolism in HK-2 cells by activating sterol regulatory element-binding protein 2 (SREBP-2 and liver X receptor (LXR, followed by an increase in 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR mediated cholesterol synthesis and low density lipoprotein receptor (LDLr mediated cholesterol uptake and a reduction in ATP-binding cassette transporter A1 (ABCA1 mediated cholesterol efflux, ultimately causing lipid accumulation in HK-2 cells. All of these responses could be suppressed by an ERS inhibitor, which suggests that CML causes lipid accumulation in renal tubule cells through ERS and that the inhibition of ERS is a potential novel approach to treating CML-induced renal tubular foam cell formation.

  13. 'Special K' and a Loss of Cell-To-Cell Adhesion in Proximal Tubule-Derived Epithelial Cells: Modulation of the Adherens Junction Complex by Ketamine

    Science.gov (United States)

    Hills, Claire E.; Jin, Tianrong; Siamantouras, Eleftherios; Liu, Issac K-K; Jefferson, Kieran P.; Squires, Paul E.

    2013-01-01

    Ketamine, a mild hallucinogenic class C drug, is the fastest growing ‘party drug’ used by 16–24 year olds in the UK. As the recreational use of Ketamine increases we are beginning to see the signs of major renal and bladder complications. To date however, we know nothing of a role for Ketamine in modulating both structure and function of the human renal proximal tubule. In the current study we have used an established model cell line for human epithelial cells of the proximal tubule (HK2) to demonstrate that Ketamine evokes early changes in expression of proteins central to the adherens junction complex. Furthermore we use AFM single-cell force spectroscopy to assess if these changes functionally uncouple cells of the proximal tubule ahead of any overt loss in epithelial cell function. Our data suggests that Ketamine (24–48 hrs) produces gross changes in cell morphology and cytoskeletal architecture towards a fibrotic phenotype. These physical changes matched the concentration-dependent (0.1–1 mg/mL) cytotoxic effect of Ketamine and reflect a loss in expression of the key adherens junction proteins epithelial (E)- and neural (N)-cadherin and β-catenin. Down-regulation of protein expression does not involve the pro-fibrotic cytokine TGFβ, nor is it regulated by the usual increase in expression of Slug or Snail, the transcriptional regulators for E-cadherin. However, the loss in E-cadherin can be partially rescued pharmacologically by blocking p38 MAPK using SB203580. These data provide compelling evidence that Ketamine alters epithelial cell-to-cell adhesion and cell-coupling in the proximal kidney via a non-classical pro-fibrotic mechanism and the data provides the first indication that this illicit substance can have major implications on renal function. Understanding Ketamine-induced renal pathology may identify targets for future therapeutic intervention. PMID:24009666

  14. Reduced linear noise approximation for biochemical reaction networks with time-scale separation: The stochastic tQSSA+

    Science.gov (United States)

    Herath, Narmada; Del Vecchio, Domitilla

    2018-03-01

    Biochemical reaction networks often involve reactions that take place on different time scales, giving rise to "slow" and "fast" system variables. This property is widely used in the analysis of systems to obtain dynamical models with reduced dimensions. In this paper, we consider stochastic dynamics of biochemical reaction networks modeled using the Linear Noise Approximation (LNA). Under time-scale separation conditions, we obtain a reduced-order LNA that approximates both the slow and fast variables in the system. We mathematically prove that the first and second moments of this reduced-order model converge to those of the full system as the time-scale separation becomes large. These mathematical results, in particular, provide a rigorous justification to the accuracy of LNA models derived using the stochastic total quasi-steady state approximation (tQSSA). Since, in contrast to the stochastic tQSSA, our reduced-order model also provides approximations for the fast variable stochastic properties, we term our method the "stochastic tQSSA+". Finally, we demonstrate the application of our approach on two biochemical network motifs found in gene-regulatory and signal transduction networks.

  15. Data-Filtering System to Avoid Total Data Distortion in IoT Networking

    Directory of Open Access Journals (Sweden)

    Dae-Young Kim

    2017-01-01

    Full Text Available In the Internet of Things (IoT networking, numerous objects are connected to a network. They sense events and deliver the sensed information to the cloud. A lot of data is generated in the IoT network, and servers in the cloud gather the sensed data from the objects. Then, the servers analyze the collected data and provide proper intelligent services to users through the results of the analysis. When the server analyzes the collected data, if there exists malfunctioning data, distortional results of the analysis will be generated. The distortional results lead to misdirection of the intelligent services, leading to poor user experience. In the analysis for intelligent services in IoT, malfunctioning data should be avoided because integrity of the collected data is crucial. Therefore, this paper proposes a data-filtering system for the server in the cloud. The proposed data-filtering system is placed in front of the server and firstly receives the sensed data from the objects. It employs the naïve Bayesian classifier and, by learning, classifies the malfunctioning data from among the collected data. Data with integrity is delivered to the server for analysis. Because the proposed system filters the malfunctioning data, the server can obtain accurate analysis results and reduce computing load. The performance of the proposed data-filtering system is evaluated through computer simulation. Through the simulation results, the efficiency of the proposed data-filtering system is shown.

  16. The calcium feedback loop and T cell activation: how cytoskeleton networks control intracellular calcium flux.

    Science.gov (United States)

    Joseph, Noah; Reicher, Barak; Barda-Saad, Mira

    2014-02-01

    During T cell activation, the engagement of a T cell with an antigen-presenting cell (APC) results in rapid cytoskeletal rearrangements and a dramatic increase of intracellular calcium (Ca(2+)) concentration, downstream to T cell antigen receptor (TCR) ligation. These events facilitate the organization of an immunological synapse (IS), which supports the redistribution of receptors, signaling molecules and organelles towards the T cell-APC interface to induce downstream signaling events, ultimately supporting T cell effector functions. Thus, Ca(2+) signaling and cytoskeleton rearrangements are essential for T cell activation and T cell-dependent immune response. Rapid release of Ca(2+) from intracellular stores, e.g. the endoplasmic reticulum (ER), triggers the opening of Ca(2+) release-activated Ca(2+) (CRAC) channels, residing in the plasma membrane. These channels facilitate a sustained influx of extracellular Ca(2+) across the plasma membrane in a process termed store-operated Ca(2+) entry (SOCE). Because CRAC channels are themselves inhibited by Ca(2+) ions, additional factors are suggested to enable the sustained Ca(2+) influx required for T cell function. Among these factors, we focus here on the contribution of the actin and microtubule cytoskeleton. The TCR-mediated increase in intracellular Ca(2+) evokes a rapid cytoskeleton-dependent polarization, which involves actin cytoskeleton rearrangements and microtubule-organizing center (MTOC) reorientation. Here, we review the molecular mechanisms of Ca(2+) flux and cytoskeletal rearrangements, and further describe the way by which the cytoskeletal networks feedback to Ca(2+) signaling by controlling the spatial and temporal distribution of Ca(2+) sources and sinks, modulating TCR-dependent Ca(2+) signals, which are required for an appropriate T cell response. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters

  17. Enabling IoT: Integration of wireless sensor network for healthcare application using Waspmote

    Science.gov (United States)

    Azmi, Noraini; Kamarudin, Latifah Munirah

    2017-03-01

    The number of patients that require medical assistance is increasing each day while staff-patient ratio is not balanced causing issues such as treatment delay and often leads to patient dissatisfaction. Besides that, healthcare devices are getting complex and challenging for it to be handled and interpreted personally by patient. Lack of staff and challenges in operating the medical devices not only affect patient in hospital but also caused problem to home care patients that require full attention and constant monitoring. This urges for a development of new method or technology. At present, Wireless Sensor Network (WSN) is gaining interest as one of the major components in enabling Internet of Things (IoT) since it offers low cost, low power monitoring besides reducing devices dependency on wires or cable. Although, WSN is initially developed for military application, nowadays, it is being integrated into various applications such as environmental monitoring, smart monitoring and agricultural monitoring. The idea of wireless monitoring with low power consumption motivates researchers to discover the possibility of deploying wireless sensor network for mission critical application such as in healthcare applications. This paper presents the details on the design and development of wireless sensor network using Waspmote from Libelium Inc. for mission critical applications such as healthcare applications.

  18. Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism

    Science.gov (United States)

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E.; Lamers, Wouter H.; Chaudhry, Farrukh A.; Verlander, Jill W.

    2016-01-01

    Glutamine synthetase (GS) catalyzes the recycling of NH4+ with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of the present study was to determine the role of PT GS in ammonia metabolism under basal conditions and during metabolic acidosis. We generated mice with PT-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Under basal conditions, PT-GS-KO increased urinary ammonia excretion significantly. Increased ammonia excretion occurred despite decreased expression of key proteins involved in renal ammonia generation. After the induction of metabolic acidosis, the ability to increase ammonia excretion was impaired significantly by PT-GS-KO. The blunted increase in ammonia excretion occurred despite greater expression of multiple components of ammonia generation, including SN1 (Slc38a3), phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and Na+-coupled electrogenic bicarbonate cotransporter. We conclude that 1) GS-mediated ammonia recycling in the PT contributes to both basal and acidosis-stimulated ammonia metabolism and 2) adaptive changes in other proteins involved in ammonia metabolism occur in response to PT-GS-KO and cause an underestimation of the role of PT GS expression. PMID:27009341

  19. A Smart and Balanced Energy-Efficient Multihop Clustering Algorithm (Smart-BEEM) for MIMO IoT Systems in Future Networks

    Science.gov (United States)

    O’Hare, Gregory M. P.; Collier, Rem

    2017-01-01

    Wireless Sensor Networks (WSNs) are typically composed of thousands of sensors powered by limited energy resources. Clustering techniques were introduced to prolong network longevity offering the promise of green computing. However, most existing work fails to consider the network coverage when evaluating the lifetime of a network. We believe that balancing the energy consumption in per unit area rather than on each single sensor can provide better-balanced power usage throughout the network. Our former work—Balanced Energy-Efficiency (BEE) and its Multihop version BEEM can not only extend the network longevity, but also maintain the network coverage. Following WSNs, Internet of Things (IoT) technology has been proposed with higher degree of diversities in terms of communication abilities and user scenarios, supporting a large range of real world applications. The IoT devices are embedded with multiple communication interfaces, normally referred as Multiple-In and Multiple-Out (MIMO) in 5G networks. The applications running on those devices can generate various types of data. Every interface has its own characteristics, which may be preferred and beneficial in some specific user scenarios. With MIMO becoming more available on the IoT devices, an advanced clustering solution for highly dynamic IoT systems is missing and also pressingly demanded in order to cater for differing user applications. In this paper, we present a smart clustering algorithm (Smart-BEEM) based on our former work BEE(M) to accomplish energy efficient and Quality of user Experience (QoE) supported communication in cluster based IoT networks. It is a user behaviour and context aware approach, aiming to facilitate IoT devices to choose beneficial communication interfaces and cluster headers for data transmission. Experimental results have proved that Smart-BEEM can further improve the performance of BEE and BEEM for coverage sensitive longevity. PMID:28678164

  20. On the Benefits and Challenges of Crowd-Sourced Network Performance Measurements for IoT Scenarios

    DEFF Research Database (Denmark)

    Mikkelsen, Lars Møller; Madsen, Tatiana Kozlova; Schwefel, Hans-Peter

    2018-01-01

    Systems within IoT domains such as ITS, Smart City, Smart Grid and other, often rely on real-time information and communication. These types of systems often include geographically distributed nodes which are connected via cellular or other wireless networks. This means great variability and unce......Systems within IoT domains such as ITS, Smart City, Smart Grid and other, often rely on real-time information and communication. These types of systems often include geographically distributed nodes which are connected via cellular or other wireless networks. This means great variability...

  1. Cytotoxic Vibrio T3SS1 Rewires Host Gene Expression to Subvert Cell Death Signaling and Activate Cell Survival Networks

    Science.gov (United States)

    De Nisco, Nicole J.; Kanchwala, Mohammed; Li, Peng; Fernandez, Jessie; Xing, Chao; Orth, Kim

    2017-01-01

    Bacterial effectors are potent manipulators of host signaling pathways. The marine bacterium Vibrio parahaemolyticus (V. para), delivers effectors into host cells through two type three secretion systems (T3SS). The ubiquitous T3SS1 is vital for V. para survival in the environment, whereas T3SS2 causes acute gastroenteritis in human hosts. Although the natural host is undefined, T3SS1 effectors attack highly conserved cellular processes and pathways to orchestrate non-apoptotic cell death. Much is known about how T3SS1 effectors function in isolation, but we wanted to understand how their concerted action globally affects host cell signaling. To assess the host response to T3SS1, we compared gene expression changes over time in primary fibroblasts infected with V. para that have a functional T3SS1 (T3SS1+) to those in cells infected with V. para lacking T3SS1 (T3SS1−). Overall, the host transcriptional response to both T3SS1+ and T3SS1− V. para was rapid, robust, and temporally dynamic. T3SS1 re-wired host gene expression by specifically altering the expression of 398 genes. Although T3SS1 effectors target host cells at the posttranslational level to cause cytotoxicity, network analysis indicated that V. para T3SS1 also precipitates a host transcriptional response that initially activates cell survival and represses cell death networks. The increased expression of several key pro-survival transcripts mediated by T3SS1 was dependent on a host signaling pathway that is silenced later in infection by the posttranslational action of T3SS1. Taken together, our analysis reveals a complex interplay between roles of T3SS1 as both a transcriptional and posttranslational manipulator of host cell signaling. PMID:28512145

  2. Single-shot T2 mapping using overlapping-echo detachment planar imaging and a deep convolutional neural network.

    Science.gov (United States)

    Cai, Congbo; Wang, Chao; Zeng, Yiqing; Cai, Shuhui; Liang, Dong; Wu, Yawen; Chen, Zhong; Ding, Xinghao; Zhong, Jianhui

    2018-04-24

    An end-to-end deep convolutional neural network (CNN) based on deep residual network (ResNet) was proposed to efficiently reconstruct reliable T 2 mapping from single-shot overlapping-echo detachment (OLED) planar imaging. The training dataset was obtained from simulations that were carried out on SPROM (Simulation with PRoduct Operator Matrix) software developed by our group. The relationship between the original OLED image containing two echo signals and the corresponding T 2 mapping was learned by ResNet training. After the ResNet was trained, it was applied to reconstruct the T 2 mapping from simulation and in vivo human brain data. Although the ResNet was trained entirely on simulated data, the trained network was generalized well to real human brain data. The results from simulation and in vivo human brain experiments show that the proposed method significantly outperforms the echo-detachment-based method. Reliable T 2 mapping with higher accuracy is achieved within 30 ms after the network has been trained, while the echo-detachment-based OLED reconstruction method took approximately 2 min. The proposed method will facilitate real-time dynamic and quantitative MR imaging via OLED sequence, and deep convolutional neural network has the potential to reconstruct maps from complex MRI sequences efficiently. © 2018 International Society for Magnetic Resonance in Medicine.

  3. N-domain angiotensin-I converting enzyme is expressed in immortalized mesangial, proximal tubule and collecting duct cells.

    Science.gov (United States)

    Mei Wang, Pamella Huey; Andrade, Maria Claudina; Quinto, Beata Marie Redublo; Di Marco, Giovana; Mortara, Renato Arruda; Vio, Carlos P; Casarini, Dulce Elena

    2015-01-01

    Somatic ACE (sACE) is found in glomerulus, proximal tubule and excreted in urine. We hypothesized that N-domain ACE can also be found at these sites. ACE profile was analyzed in mesangial (IMC), proximal (LLC-PK1), distal tubule (MDCK) and collecting duct (IMCD) cells. Cell lysate and culture medium were submitted to gel filtration chromatography, which separated two peaks with ACE activity from cells and medium, except from distal tubule. The first had a high molecular weight and the second, a lower one (65 kDa; N-domain ACE). We focused on N-domain ACE purification and characterization from LLC-PK1. Total LLC-PK1 N-domain ACE purification was achieved by ion-exchange chromatography, which presented only one peak with ACE activity, denominated ACE(int2A). ACE(int2A) activity was influenced by pH, NaCl and temperature. The purified enzyme was inhibited by Captopril and hydrolyzed AngI, Ang1-7 and AcSDKP. Its ability to hydrolyze AcSDKP characterized it as an N-domain ACE. ACE(int2A) also presented high amino acid sequence homology with the N-terminal part of sACE from mouse, rat, human and rabbit. The presence of secreted and intracellular N-domain ACE and sACE in IMC, LLC-PK1 and IMCD cells confirmed our studies along the nephron. We identified, purified and characterized N-domain ACE from LLC-PK1. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Increased T-regulatory cells within lymphocyte follicles in moderate COPD

    DEFF Research Database (Denmark)

    Plumb, J; Smyth, L J C; Adams, H R

    2009-01-01

    Lymphoid follicles in the lung parenchyma are a characteristic feature of chronic obstructive pulmonary disease (COPD). There are reports of altered CD4 T-regulatory cell numbers in COPD lungs, but the location of these cells within COPD lung tissue specific follicles has not been investigated......, as well as lymphoid clusters lacking organisation. The percentage of CD4 cells that were T-regulatory cells were significantly increased (p = 0.02) within COPD (16%) follicles compared with smokers (10%) and nonsmokers (8%). In contrast, there was no change (p>0.05) in the percentage of T-regulatory cells...... in clusters or the subepithelium between groups. Lymphoid follicles in COPD patients have increased T-regulatory cells. Therefore, T-regulatory activity may be altered within COPD lymphoid follicles....

  5. Direct physical contact between intercalated cells in the distal convoluted tubule and the afferent arteriole in mouse kidneys.

    Directory of Open Access Journals (Sweden)

    Hao Ren

    Full Text Available Recent physiological studies in the kidney proposed the existence of a secondary feedback mechanism termed 'crosstalk' localized after the macula densa. This newly discovered crosstalk contact between the nephron tubule and its own afferent arteriole may potentially revolutionize our understanding of renal vascular resistance and electrolyte regulation. However, the nature of such a crosstalk mechanism is still debated due to a lack of direct and comprehensive morphological evidence. Its exact location along the nephron, its prevalence among the different types of nephrons, and the type of cells involved are yet unknown. To address these issues, computer assisted 3-dimensional nephron tracing was applied in combination with direct immunohistochemistry on plastic sections and electron microscopy. 'Random' contacts in the cortex were identified by the tracing and excluded. We investigated a total of 168 nephrons from all cortical regions. The results demonstrated that the crosstalk contact existed, and that it was only present in certain nephrons (90% of the short-looped and 75% of the long-looped nephrons. The crosstalk contacts always occurred at a specific position--the last 10% of the distal convoluted tubule. Importantly, we demonstrated, for the first time, that the cells found in the tubule wall at the contact site were always type nonA-nonB intercalated cells. In conclusion, the present work confirmed the existence of a post macula densa physical crosstalk contact.

  6. Direct physical contact between intercalated cells in the distal convoluted tubule and the afferent arteriole in mouse kidneys.

    Science.gov (United States)

    Ren, Hao; Liu, Ning-Yu; Andreasen, Arne; Thomsen, Jesper S; Cao, Liu; Christensen, Erik I; Zhai, Xiao-Yue

    2013-01-01

    Recent physiological studies in the kidney proposed the existence of a secondary feedback mechanism termed 'crosstalk' localized after the macula densa. This newly discovered crosstalk contact between the nephron tubule and its own afferent arteriole may potentially revolutionize our understanding of renal vascular resistance and electrolyte regulation. However, the nature of such a crosstalk mechanism is still debated due to a lack of direct and comprehensive morphological evidence. Its exact location along the nephron, its prevalence among the different types of nephrons, and the type of cells involved are yet unknown. To address these issues, computer assisted 3-dimensional nephron tracing was applied in combination with direct immunohistochemistry on plastic sections and electron microscopy. 'Random' contacts in the cortex were identified by the tracing and excluded. We investigated a total of 168 nephrons from all cortical regions. The results demonstrated that the crosstalk contact existed, and that it was only present in certain nephrons (90% of the short-looped and 75% of the long-looped nephrons). The crosstalk contacts always occurred at a specific position--the last 10% of the distal convoluted tubule. Importantly, we demonstrated, for the first time, that the cells found in the tubule wall at the contact site were always type nonA-nonB intercalated cells. In conclusion, the present work confirmed the existence of a post macula densa physical crosstalk contact.

  7. Community intervention to increase neighborhood social network among Japanese older adults.

    Science.gov (United States)

    Harada, Kazuhiro; Masumoto, Kouhei; Katagiri, Keiko; Fukuzawa, Ai; Chogahara, Makoto; Kondo, Narihiko; Okada, Shuichi

    2018-03-01

    Strengthening neighborhood social networks is important for promoting health among older adults. However, effective intervention strategies aimed at increasing older adults' social networks have not yet been established. The present study examined whether a university-led community intervention that provided communication opportunities could increase older Japanese adults' neighborhood social networks. The present study used a quasi-experimental design. Before the intervention, using postal mail, we carried out a baseline questionnaire survey that was sent to all people living in the Tsurukabuto community aged ≥60 years (n = 1769), of whom 1068 responded. For the community intervention, 18 event-based programs were provided over the course of 1 year at Kobe University. Academic staff at Kobe University organized all the programs. During the program, social interactions among participants were promoted. A follow-up survey was distributed to those who responded to the baseline survey, and 710 individuals answered the question about their participation in the intervention programs (138 respondents were participants, 572 were non-participants). The neighborhood social network was measured in both the baseline and follow-up surveys. Analysis of covariance showed that the changes in neighborhood social network among participants in the program was significantly higher than the changes among non-participants (P = 0.046) after adjusting for the baseline score of social network. The present study found that participants of the intervention expanded their neighborhood social network, but non-participants did not. This finding shows that community interventions using university resources could increase older adults' neighborhood social networks. Geriatr Gerontol Int 2018; 18: 462-469. © 2017 Japan Geriatrics Society.

  8. Prenatal programming of rat cortical collecting tubule sodium transport.

    Science.gov (United States)

    Cheng, Chih-Jen; Lozano, German; Baum, Michel

    2012-03-15

    Prenatal insults have been shown to lead to elevated blood pressure in offspring when they are studied as adults. Prenatal administration of dexamethasone and dietary protein deprivation have demonstrated that there is an increase in transporter abundance for a number of nephron segments but not the subunits of the epithelial sodium channel (ENaC) in the cortical collecting duct. Recent studies have shown that aldosterone is elevated in offspring of protein-deprived mothers when studied as adults, but the physiological importance of the increase in serum aldosterone is unknown. As an indirect measure of ENaC activity, we compared the natriuretic response to benzamil in offspring of mothers who ate a low-protein diet (6%) with those who ate a normal diet (20%) for the last half of pregnancy. The natriuretic response to benzamil was greater in the 6% group (821.1 ± 161.0 μmol/24 h) compared with the 20% group (279.1 ± 137.0 μmol/24 h), consistent with greater ENaC activity in vivo (P sodium transport (-1.9 ± 3.1 pmol·mm(-1)·min(-1)), the offspring of rats that ate a 6% protein diet during the last half of pregnancy had a net sodium flux of 10.7 ± 2.6 pmol·mm(-1)·min(-1) (P = 0.01) in tubules perfused in vitro. Sodium transport was measured using ion-selective electrodes, a novel technique allowing measurement of sodium in nanoliter quantities of fluid. Thus we directly demonstrate that there is prenatal programming of cortical collecting duct sodium transport.

  9. Study of the permeability of the various parts of the tubules to sodium and potassium ions

    International Nuclear Information System (INIS)

    Morel, F.; Falbriard, A.

    1959-01-01

    The method of stop flow analysis has been used in rabbits together with radioactive sodium and potassium injected in the middle of a six minutes period of arrest of urine flow during an osmotic diuresis. Urine was subsequently collected in 60 ta 80 mg samples. The specific activities of sodium and potassium suggest that both ions pass directly from the renal interstitial tissue into the urine at different and distinct areas in the tubules. The whole distal segment, including the area of active reabsorption of this ion, is impermeable to sodium in the direction interstitial tissue to lumen. The adjacent, more proximal tubule is, however, extremely permeable. The distal tubular impermeability to potassium is more limited. The specific activity already having reached a maximum at the level of active sodium reabsorption. Reprint of a paper published in 'Revue Francaise d'Etudes Cliniques et Biologiques', n. 5, vol IV, p. 471-474 [fr

  10. Intermittent exploration on a scale-free network

    International Nuclear Information System (INIS)

    Ramezanpour, A

    2007-02-01

    We study an intermittent random walk on a random network of scale-free degree distribution. The walk is a combination of simple random walks of duration t w and random long-range jumps. While the time the walker needs to cover all the nodes increases with t w , the corresponding time for the edges displays a non monotonic behavior with a minimum for some nontrivial value of t w . This is a heterogeneity-induced effect that is not observed in homogeneous small-world networks. The optimal t w increases with the degree of assortativity in the network. Depending on the nature of degree correlations and the elapsed time the walker finds an over/underestimate of the degree distribution exponent. (author)

  11. The Use of Wireless Sensor Network for Increasing Airport Safety

    Directory of Open Access Journals (Sweden)

    Jakub Kraus

    2013-09-01

    Full Text Available This article deals with the use of wireless sensor networks for increasing safety at airports, respectively for replacing the current monitoring system to ensure safety. The article describes sensor networks and their applications to the identified processes and consideration of financial and safety benefits.

  12. Leucine-rich repeat kinase 2 (LRRK2-deficient rats exhibit renal tubule injury and perturbations in metabolic and immunological homeostasis.

    Directory of Open Access Journals (Sweden)

    Daniel Ness

    Full Text Available Genetic evidence links mutations in the LRRK2 gene with an increased risk of Parkinson's disease, for which no neuroprotective or neurorestorative therapies currently exist. While the role of LRRK2 in normal cellular function has yet to be fully described, evidence suggests involvement with immune and kidney functions. A comparative study of LRRK2-deficient and wild type rats investigated the influence that this gene has on the phenotype of these rats. Significant weight gain in the LRRK2 null rats was observed and was accompanied by significant increases in insulin and insulin-like growth factors. Additionally, LRRK2-deficient rats displayed kidney morphological and histopathological alterations in the renal tubule epithelial cells of all animals assessed. These perturbations in renal morphology were accompanied by significant decreases of lipocalin-2, in both the urine and plasma of knockout animals. Significant alterations in the cellular composition of the spleen between LRRK2 knockout and wild type animals were identified by immunophenotyping and were associated with subtle differences in response to dual infection with rat-adapted influenza virus (RAIV and Streptococcus pneumoniae. Ontological pathway analysis of LRRK2 across metabolic and kidney processes and pathological categories suggested that the thioredoxin network may play a role in perturbing these organ systems. The phenotype of the LRRK2 null rat is suggestive of a complex biology influencing metabolism, immune function and kidney homeostasis. These data need to be extended to better understand the role of the kinase domain or other biological functions of the gene to better inform the development of pharmacological inhibitors.

  13. Experimental type II diabetes and related models of impaired glucose metabolism differentially regulate glucose transporters at the proximal tubule brush border membrane.

    Science.gov (United States)

    Chichger, Havovi; Cleasby, Mark E; Srai, Surjit K; Unwin, Robert J; Debnam, Edward S; Marks, Joanne

    2016-06-01

    What is the central question of this study? Although SGLT2 inhibitors represent a promising treatment for patients suffering from diabetic nephropathy, the influence of metabolic disruption on the expression and function of glucose transporters is largely unknown. What is the main finding and its importance? In vivo models of metabolic disruption (Goto-Kakizaki type II diabetic rat and junk-food diet) demonstrate increased expression of SGLT1, SGLT2 and GLUT2 in the proximal tubule brush border. In the type II diabetic model, this is accompanied by increased SGLT- and GLUT-mediated glucose uptake. A fasted model of metabolic disruption (high-fat diet) demonstrated increased GLUT2 expression only. The differential alterations of glucose transporters in response to varying metabolic stress offer insight into the therapeutic value of inhibitors. SGLT2 inhibitors are now in clinical use to reduce hyperglycaemia in type II diabetes. However, renal glucose reabsorption across the brush border membrane (BBM) is not completely understood in diabetes. Increased consumption of a Western diet is strongly linked to type II diabetes. This study aimed to investigate the adaptations that occur in renal glucose transporters in response to experimental models of diet-induced insulin resistance. The study used Goto-Kakizaki type II diabetic rats and normal rats rendered insulin resistant using junk-food or high-fat diets. Levels of protein kinase C-βI (PKC-βI), GLUT2, SGLT1 and SGLT2 were determined by Western blotting of purified renal BBM. GLUT- and SGLT-mediated d-[(3) H]glucose uptake by BBM vesicles was measured in the presence and absence of the SGLT inhibitor phlorizin. GLUT- and SGLT-mediated glucose transport was elevated in type II diabetic rats, accompanied by increased expression of GLUT2, its upstream regulator PKC-βI and SGLT1 protein. Junk-food and high-fat diet feeding also caused higher membrane expression of GLUT2 and its upstream regulator PKC

  14. Data Gathering and Energy Transfer Dilemma in UAV-Assisted Flying Access Network for IoT.

    Science.gov (United States)

    Arabi, Sara; Sabir, Essaid; Elbiaze, Halima; Sadik, Mohamed

    2018-05-11

    Recently, Unmanned Aerial Vehicles (UAVs) have emerged as an alternative solution to assist wireless networks, thanks to numerous advantages they offer in comparison to terrestrial fixed base stations. For instance, a UAV can be used to embed a flying base station providing an on-demand nomadic access to network services. A UAV can also be used to wirelessly recharge out-of-battery ground devices. In this paper, we aim to deal with both data collection and recharging depleted ground Internet-of-Things (IoT) devices through a UAV station used as a flying base station. To extend the network lifetime, we present a novel use of UAV with energy harvesting module and wireless recharging capabilities. However, the UAV is used as an energy source to empower depleted IoT devices. On one hand, the UAV charges depleted ground IoT devices under three policies: (1) low-battery first scheme; (2) high-battery first scheme; and (3) random scheme. On the other hand, the UAV station collects data from IoT devices that have sufficient energy to transmit their packets, and in the same phase, the UAV exploits the Radio Frequency (RF) signals transmitted by IoT devices to extract and harvest energy. Furthermore, and as the UAV station has a limited coverage time due to its energy constraints, we propose and investigate an efficient trade-off between ground users recharging time and data gathering time. Furthermore, we suggest to control and optimize the UAV trajectory in order to complete its travel within a minimum time, while minimizing the energy spent and/or enhancing the network lifetime. Extensive numerical results and simulations show how the system behaves under different scenarios and using various metrics in which we examine the added value of UAV with energy harvesting module.

  15. Data Gathering and Energy Transfer Dilemma in UAV-Assisted Flying Access Network for IoT

    Directory of Open Access Journals (Sweden)

    Sara Arabi

    2018-05-01

    Full Text Available Recently, Unmanned Aerial Vehicles (UAVs have emerged as an alternative solution to assist wireless networks, thanks to numerous advantages they offer in comparison to terrestrial fixed base stations. For instance, a UAV can be used to embed a flying base station providing an on-demand nomadic access to network services. A UAV can also be used to wirelessly recharge out-of-battery ground devices. In this paper, we aim to deal with both data collection and recharging depleted ground Internet-of-Things (IoT devices through a UAV station used as a flying base station. To extend the network lifetime, we present a novel use of UAV with energy harvesting module and wireless recharging capabilities. However, the UAV is used as an energy source to empower depleted IoT devices. On one hand, the UAV charges depleted ground IoT devices under three policies: (1 low-battery first scheme; (2 high-battery first scheme; and (3 random scheme. On the other hand, the UAV station collects data from IoT devices that have sufficient energy to transmit their packets, and in the same phase, the UAV exploits the Radio Frequency (RF signals transmitted by IoT devices to extract and harvest energy. Furthermore, and as the UAV station has a limited coverage time due to its energy constraints, we propose and investigate an efficient trade-off between ground users recharging time and data gathering time. Furthermore, we suggest to control and optimize the UAV trajectory in order to complete its travel within a minimum time, while minimizing the energy spent and/or enhancing the network lifetime. Extensive numerical results and simulations show how the system behaves under different scenarios and using various metrics in which we examine the added value of UAV with energy harvesting module.

  16. Distinct mechanisms underlie adaptation of proximal tubule Na+/H+ exchanger isoform 3 in response to chronic metabolic and respiratory acidosis.

    Science.gov (United States)

    Silva, Pedro Henrique Imenez; Girardi, Adriana Castello Costa; Neri, Elida Adalgisa; Rebouças, Nancy Amaral

    2012-04-01

    The Na(+/)H(+) exchanger isoform 3 (NHE3) is essential for HCO(3)(-) reabsorption in renal proximal tubules. The expression and function of NHE3 must adapt to acid-base conditions. The goal of this study was to elucidate the mechanisms responsible for higher proton secretion in proximal tubules during acidosis and to evaluate whether there are differences between metabolic and respiratory acidosis with regard to NHE3 modulation and, if so, to identify the relevant parameters that may trigger these distinct adaptive responses. We achieved metabolic acidosis by lowering HCO(3)(-) concentration in the cell culture medium and respiratory acidosis by increasing CO(2) tension in the incubator chamber. We found that cell-surface NHE3 expression was increased in response to both forms of acidosis. Mild (pH 7.21 ± 0.02) and severe (6.95 ± 0.07) metabolic acidosis increased mRNA levels, at least in part due to up-regulation of transcription, whilst mild (7.11 ± 0.03) and severe (6.86 ± 0.01) respiratory acidosis did not up-regulate NHE3 expression. Analyses of the Nhe3 promoter region suggested that the regulatory elements sensitive to metabolic acidosis are located between -466 and -153 bp, where two consensus binding sites for SP1, a transcription factor up-regulated in metabolic acidosis, were localised. We conclude that metabolic acidosis induces Nhe3 promoter activation, which results in higher mRNA and total protein level. At the plasma membrane surface, NHE3 expression was increased in metabolic and respiratory acidosis alike, suggesting that low pH is responsible for NHE3 displacement to the cell surface.

  17. Time reversibility of quantum diffusion in small-world networks

    Science.gov (United States)

    Han, Sung-Guk; Kim, Beom Jun

    2012-02-01

    We study the time-reversal dynamics of a tight-binding electron in the Watts-Strogatz (WS) small-world networks. The localized initial wave packet at time t = 0 diffuses as time proceeds until the time-reversal operation, together with the momentum perturbation of the strength η, is made at the reversal time T. The time irreversibility is measured by I = |Π( t = 2 T) - Π( t = 0)|, where Π is the participation ratio gauging the extendedness of the wavefunction and for convenience, t is measured forward even after the time reversal. When η = 0, the time evolution after T makes the wavefunction at t = 2 T identical to the one at t = 0, and we find I = 0, implying a null irreversibility or a complete reversibility. On the other hand, as η is increased from zero, the reversibility becomes weaker, and we observe enhancement of the irreversibility. We find that I linearly increases with increasing η in the weakly-perturbed region, and that the irreversibility is much stronger in the WS network than in the local regular network.

  18. The adult Drosophila malphigian tubules are maintained by multipotent stem cells | Center for Cancer Research

    Science.gov (United States)

    All animals must excrete the waste products of metabolism. Excretion is performed by the kidney in vertebrates and by the Malpighian tubules in Drosophila. The mammalian kidney has an inherent ability for recovery and regeneration after ischemic injury. Stem cells and progenitor cells have been proposed to be responsible for repair and regeneration of injured renal tissue.

  19. Lifetime Maximization via Hole Alleviation in IoT Enabling Heterogeneous Wireless Sensor Networks.

    Science.gov (United States)

    Wadud, Zahid; Javaid, Nadeem; Khan, Muhammad Awais; Alrajeh, Nabil; Alabed, Mohamad Souheil; Guizani, Nadra

    2017-07-21

    In Internet of Things (IoT) enabled Wireless Sensor Networks (WSNs), there are two major factors which degrade the performance of the network. One is the void hole which occurs in a particular region due to unavailability of forwarder nodes. The other is the presence of energy hole which occurs due to imbalanced data traffic load on intermediate nodes. Therefore, an optimum transmission strategy is required to maximize the network lifespan via hole alleviation. In this regard, we propose a heterogeneous network solution that is capable to balance energy dissipation among network nodes. In addition, the divide and conquer approach is exploited to evenly distribute number of transmissions over various network areas. An efficient forwarder node selection is performed to alleviate coverage and energy holes. Linear optimization is performed to validate the effectiveness of our proposed work in term of energy minimization. Furthermore, simulations are conducted to show that our claims are well grounded. Results show the superiority of our work as compared to the baseline scheme in terms of energy consumption and network lifetime.

  20. PANATIKI: A Network Access Control Implementation Based on PANA for IoT Devices

    Directory of Open Access Journals (Sweden)

    Antonio F. Gomez Skarmeta

    2013-11-01

    Full Text Available Internet of Things (IoT networks are the pillar of recent novel scenarios, such as smart cities or e-healthcare applications. Among other challenges, these networks cover the deployment and interaction of small devices with constrained capabilities and Internet protocol (IP-based networking connectivity. These constrained devices usually require connection to the Internet to exchange information (e.g., management or sensing data or access network services. However, only authenticated and authorized devices can, in general, establish this connection. The so-called authentication, authorization and accounting (AAA services are in charge of performing these tasks on the Internet. Thus, it is necessary to deploy protocols that allow constrained devices to verify their credentials against AAA infrastructures. The Protocol for Carrying Authentication for Network Access (PANA has been standardized by the Internet engineering task force (IETF to carry the Extensible Authentication Protocol (EAP, which provides flexible authentication upon the presence of AAA. To the best of our knowledge, this paper is the first deep study of the feasibility of EAP/PANA for network access control in constrained devices. We provide light-weight versions and implementations of these protocols to fit them into constrained devices. These versions have been designed to reduce the impact in standard specifications. The goal of this work is two-fold: (1 to demonstrate the feasibility of EAP/PANA in IoT devices; (2 to provide the scientific community with the first light-weight interoperable implementation of EAP/PANA for constrained devices in the Contiki operating system (Contiki OS, called PANATIKI. The paper also shows a testbed, simulations and experimental results obtained from real and simulated constrained devices.

  1. PANATIKI: a network access control implementation based on PANA for IoT devices.

    Science.gov (United States)

    Moreno Sanchez, Pedro; Marin Lopez, Rafa; Gomez Skarmeta, Antonio F

    2013-11-01

    Internet of Things (IoT) networks are the pillar of recent novel scenarios, such as smart cities or e-healthcare applications. Among other challenges, these networks cover the deployment and interaction of small devices with constrained capabilities and Internet protocol (IP)-based networking connectivity. These constrained devices usually require connection to the Internet to exchange information (e.g., management or sensing data) or access network services. However, only authenticated and authorized devices can, in general, establish this connection. The so-called authentication, authorization and accounting (AAA) services are in charge of performing these tasks on the Internet. Thus, it is necessary to deploy protocols that allow constrained devices to verify their credentials against AAA infrastructures. The Protocol for Carrying Authentication for Network Access (PANA) has been standardized by the Internet engineering task force (IETF) to carry the Extensible Authentication Protocol (EAP), which provides flexible authentication upon the presence of AAA. To the best of our knowledge, this paper is the first deep study of the feasibility of EAP/PANA for network access control in constrained devices. We provide light-weight versions and implementations of these protocols to fit them into constrained devices. These versions have been designed to reduce the impact in standard specifications. The goal of this work is two-fold: (1) to demonstrate the feasibility of EAP/PANA in IoT devices; (2) to provide the scientific community with the first light-weight interoperable implementation of EAP/PANA for constrained devices in the Contiki operating system (Contiki OS), called PANATIKI. The paper also shows a testbed, simulations and experimental results obtained from real and simulated constrained devices.

  2. Internet of Things (IoT) Based Design of a Secure and Lightweight Body Area Network (BAN) Healthcare System.

    Science.gov (United States)

    Deng, Yong-Yuan; Chen, Chin-Ling; Tsaur, Woei-Jiunn; Tang, Yung-Wen; Chen, Jung-Hsuan

    2017-12-15

    As sensor networks and cloud computation technologies have rapidly developed over recent years, many services and applications integrating these technologies into daily life have come together as an Internet of Things (IoT). At the same time, aging populations have increased the need for expanded and more efficient elderly care services. Fortunately, elderly people can now wear sensing devices which relay data to a personal wireless device, forming a body area network (BAN). These personal wireless devices collect and integrate patients' personal physiological data, and then transmit the data to the backend of the network for related diagnostics. However, a great deal of the information transmitted by such systems is sensitive data, and must therefore be subject to stringent security protocols. Protecting this data from unauthorized access is thus an important issue in IoT-related research. In regard to a cloud healthcare environment, scholars have proposed a secure mechanism to protect sensitive patient information. Their schemes provide a general architecture; however, these previous schemes still have some vulnerability, and thus cannot guarantee complete security. This paper proposes a secure and lightweight body-sensor network based on the Internet of Things for cloud healthcare environments, in order to address the vulnerabilities discovered in previous schemes. The proposed authentication mechanism is applied to a medical reader to provide a more comprehensive architecture while also providing mutual authentication, and guaranteeing data integrity, user untraceability, and forward and backward secrecy, in addition to being resistant to replay attack.

  3. Protective Effect of Urtica dioica L. (Urticaceae) on Morphometric and Morphologic Alterations of Seminiferous Tubules in STZ Diabetic Rats.

    Science.gov (United States)

    Golalipour, Mohammad Jafar; Kabiri Balajadeh, Babak; Ghafari, Soraya; Azarhosh, Ramin; Khori, Vahid

    2011-09-01

    Urtica dioica L. has been known as a medicinal plant in the world. This study was conducted to determine the effects of the hydroalcoholic extract of Urtica dioica leaves on seminiferous tubules of diabetic rats. Animals were allocated to control, diabetic and protective groups. Treated animals received extract of U. dioica (100 mg/ kg/ day) IP for the first 5 days and STZ injection on the 6th day. After 5 weeks, testes removed and stained with H&E technique. Tubular cell disintegration, sertoli and spermatogonia cell vacuolization, and decrease in sperm concentration observed in diabetic in comparison with control and protective groups. External seminiferous tubular diameter and seminiferous epithelial height significantly reduced (Pdioica, before induction of diabetes; has protective role on seminiferous tubules alterations.

  4. The myopathy-causing mutation DNM2-S619L leads to defective tubulation in vitro and in developing zebrafish

    Directory of Open Access Journals (Sweden)

    Elizabeth M. Gibbs

    2014-01-01

    Full Text Available DNM2 is a ubiquitously expressed GTPase that regulates multiple subcellular processes. Mutations in DNM2 are a common cause of centronuclear myopathy, a severe disorder characterized by altered skeletal muscle structure and function. The precise mechanisms underlying disease-associated DNM2 mutations are unresolved. We examined the common DNM2-S619L mutation using both in vitro and in vivo approaches. Expression of DNM2-S619L in zebrafish led to the accumulation of aberrant vesicular structures and to defective excitation-contraction coupling. Expression of DNM2-S619L in COS7 cells resulted in defective BIN1-dependent tubule formation. These data suggest that DNM2-S619L causes disease, in part, by interfering with membrane tubulation.

  5. Big Data Clustering via Community Detection and Hyperbolic Network Embedding in IoT Applications.

    Science.gov (United States)

    Karyotis, Vasileios; Tsitseklis, Konstantinos; Sotiropoulos, Konstantinos; Papavassiliou, Symeon

    2018-04-15

    In this paper, we present a novel data clustering framework for big sensory data produced by IoT applications. Based on a network representation of the relations among multi-dimensional data, data clustering is mapped to node clustering over the produced data graphs. To address the potential very large scale of such datasets/graphs that test the limits of state-of-the-art approaches, we map the problem of data clustering to a community detection one over the corresponding data graphs. Specifically, we propose a novel computational approach for enhancing the traditional Girvan-Newman (GN) community detection algorithm via hyperbolic network embedding. The data dependency graph is embedded in the hyperbolic space via Rigel embedding, allowing more efficient computation of edge-betweenness centrality needed in the GN algorithm. This allows for more efficient clustering of the nodes of the data graph in terms of modularity, without sacrificing considerable accuracy. In order to study the operation of our approach with respect to enhancing GN community detection, we employ various representative types of artificial complex networks, such as scale-free, small-world and random geometric topologies, and frequently-employed benchmark datasets for demonstrating its efficacy in terms of data clustering via community detection. Furthermore, we provide a proof-of-concept evaluation by applying the proposed framework over multi-dimensional datasets obtained from an operational smart-city/building IoT infrastructure provided by the Federated Interoperable Semantic IoT/cloud Testbeds and Applications (FIESTA-IoT) testbed federation. It is shown that the proposed framework can be indeed used for community detection/data clustering and exploited in various other IoT applications, such as performing more energy-efficient smart-city/building sensing.

  6. Tools-4-Metatool (T4M): online suite of web-tools to process stoichiometric network analysis data from Metatool.

    Science.gov (United States)

    Xavier, Daniela; Vázquez, Sara; Higuera, Clara; Morán, Federico; Montero, Francisco

    2011-08-01

    Tools-4-Metatool (T4M) is a suite of web-tools, implemented in PERL, which analyses, parses, and manipulates files related to Metatool. Its main goal is to assist the work with Metatool. T4M has two major sets of tools: Analysis and Compare. Analysis visualizes the results of Metatool (convex basis, elementary flux modes, and enzyme subsets) and facilitates the study of metabolic networks. It is composed of five tools: MDigraph, MetaMatrix, CBGraph, EMGraph, and SortEM. Compare was developed to compare different Metatool results from different networks. This set consists of: Compara and ComparaSub which compare network subsets providing outputs in different formats and ComparaEM that seeks for identical elementary modes in two metabolic networks. The suite T4M also includes one script that generates Metatool input: CBasis2Metatool, based on a Metatool output file that is filtered by a list of convex basis' metabolites. Finally, the utility CheckMIn checks the consistency of the Metatool input file. T4M is available at http://solea.quim.ucm.es/t4m. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  7. Reconstruction of t anti tH (H → bb) events using deep neural networks with the CMS detector

    Energy Technology Data Exchange (ETDEWEB)

    Rieger, Marcel; Erdmann, Martin; Fischer, Benjamin; Fischer, Robert; Heidemann, Fabian; Quast, Thorben; Rath, Yannik [III. Physikalisches Institut A, RWTH Aachen University (Germany)

    2016-07-01

    The measurement of Higgs boson production in association with top-quark pairs (t anti tH) is an important goal of Run 2 of the LHC as it allows for a direct measurement of the underlying Yukawa coupling. Due to the complex final state, however, the analysis of semi-leptonic t anti tH events with the Higgs boson decaying into a pair of bottom-quarks is challenging. A promising method for tackling jet parton associations are Deep Neural Networks (DNN). While being a widely spread machine learning algorithm in modern industry, DNNs are on the way to becoming established in high energy physics. We present a study on the reconstruction of the final state using DNNs, comparing to Boosted Decision Trees (BDT) as benchmark scenario. This is accomplished by generating permutations of simulated events and comparing them with truth information to extract reconstruction efficiencies.

  8. Effect of Tamoxifen on Seminiferous Tubules Structure during Pregnancy in Adult Mice

    Directory of Open Access Journals (Sweden)

    J Soleimani Rad

    2016-03-01

    Full Text Available Introduction: Tamoxifen is a nonsteroidal drug which mainly treats breast cancer. It is also applied for stimulation of ovulation and remedy of infertility. Regarding the tamoxifen binding to estrogen receptors and the possible role of estrogens in spermatogenesis, the present study aimed to histologically evaluate spermatogenesis in the seminiferous ducts of mice, whose mothers had received tamoxifen during pregnancy. Methods: In the present study, 30 female and 15 male mice of NMRI race were selected for mating. Since 13th day of pregnancy, the experimental group received tamoxifen with the dosage of 5 mg/kg intra-peritoneally for 7 days, wherease the control group received normal saline. After childbirth of the mated mice, male infants were selected and monitored in the standard laboratory conditions. After reaching the age of puberty (6-8Weeks, adult mice were sacrificed by the cervical dislocation, and the testes were removed for histological evaluation of spermatogenesis. After routine histological processing, the samples were studied by the light microscope. Results: Histological studies showed that spermatogenic and Sertoli cells in the seminiferous tubules in control and experimental groups were significantly different, though no difference was observed in the number of Leydig cells in the both groups. Conclusion: The findings of the present study showed that tamoxifen exposure during development can cause histological changes in the seminiferous tubules, which can lead to infertility in the male rat.

  9. Vitality of Enterococcus faecalis inside dentinal tubules after five root canal disinfection methods

    OpenAIRE

    Vatkar, Niranjan Ashok; Hegde, Vivek; Sathe, Sucheta

    2016-01-01

    Aim: To compare the vitality of Enterococcus faecalis within dentinal tubules after subjected to five root canal disinfection methods. Materials and Methods: Dentin blocks (n = 60) were colonized with E. faecalis. After 4 weeks of incubation, the dentin blocks were divided into one control and five test groups (n = 10 each). The root canals of test groups were subjected to one of the disinfection methods, namely, normal saline (NS), sodium hypochlorite (NaOCl), chlorhexidine digluconate (C...

  10. Pb exposure attenuates hypersensitivity in vivo by increasing regulatory T cells

    International Nuclear Information System (INIS)

    Fang, Liang; Zhao, Fang; Shen, Xuefeng; Ouyang, Weiming; Liu, Xinqin; Xu, Yan; Yu, Tao; Jin, Boquan; Chen, Jingyuan; Luo, Wenjing

    2012-01-01

    Pb is a common environmental pollutant affecting various organs. Exposure of the immune system to Pb leads to immunosuppression or immunodysregulation. Although previous studies showed that Pb exposure can modulate the function of helper T cells, Pb immunotoxicity remains incompletely understood. In this study, we investigated the effect of Pb exposure on T cell development, and the underlying mechanism of Pb-induced suppression of the delayed-type hypersensitivity (DTH) response in vivo. Sprague–Dawley rats were exposed to 300 ppm Pb-acetate solution via the drinking water for six weeks, and we found that Pb exposure significantly increased Pb concentrations in the blood by 4.2-fold (p + CD8 − and peripheral CD4 + T cells was significantly reduced, whereas, CD8 + population was not affected. In contrast to conventional CD4 + T cells, Foxp3 + regulatory T cells (Tregs) were increased in both the thymus and peripheral lymphoid organs of Pb-exposed rats. In line with the increase of Tregs, the DTH response of Pb-exposed rats was markedly suppressed. Depletion of Tregs reversed the suppression of DTH response by Pb-exposed CD4 + T cells in an adoptive transfer model, suggesting a critical role of the increased Tregs in suppressing the DTH response. Collectively, this study revealed that Pb-exposure may upregulate Tregs, thereby leading to immunosuppression. -- Highlights: ► Pb exposure impaired CD4 + thymic T cell development. ► Peripheral T lymphocytes were reduced following Pb exposure. ► Pb exposure increases thymic and peripheral Treg cells in rats. ► Tregs played a critical role in Pb-exposure-induced immune suppression.

  11. Design of Compressed Sensing Algorithm for Coal Mine IoT Moving Measurement Data Based on a Multi-Hop Network and Total Variation

    Directory of Open Access Journals (Sweden)

    Gang Wang

    2018-05-01

    Full Text Available As the application of a coal mine Internet of Things (IoT, mobile measurement devices, such as intelligent mine lamps, cause moving measurement data to be increased. How to transmit these large amounts of mobile measurement data effectively has become an urgent problem. This paper presents a compressed sensing algorithm for the large amount of coal mine IoT moving measurement data based on a multi-hop network and total variation. By taking gas data in mobile measurement data as an example, two network models for the transmission of gas data flow, namely single-hop and multi-hop transmission modes, are investigated in depth, and a gas data compressed sensing collection model is built based on a multi-hop network. To utilize the sparse characteristics of gas data, the concept of total variation is introduced and a high-efficiency gas data compression and reconstruction method based on Total Variation Sparsity based on Multi-Hop (TVS-MH is proposed. According to the simulation results, by using the proposed method, the moving measurement data flow from an underground distributed mobile network can be acquired and transmitted efficiently.

  12. Design of Compressed Sensing Algorithm for Coal Mine IoT Moving Measurement Data Based on a Multi-Hop Network and Total Variation.

    Science.gov (United States)

    Wang, Gang; Zhao, Zhikai; Ning, Yongjie

    2018-05-28

    As the application of a coal mine Internet of Things (IoT), mobile measurement devices, such as intelligent mine lamps, cause moving measurement data to be increased. How to transmit these large amounts of mobile measurement data effectively has become an urgent problem. This paper presents a compressed sensing algorithm for the large amount of coal mine IoT moving measurement data based on a multi-hop network and total variation. By taking gas data in mobile measurement data as an example, two network models for the transmission of gas data flow, namely single-hop and multi-hop transmission modes, are investigated in depth, and a gas data compressed sensing collection model is built based on a multi-hop network. To utilize the sparse characteristics of gas data, the concept of total variation is introduced and a high-efficiency gas data compression and reconstruction method based on Total Variation Sparsity based on Multi-Hop (TVS-MH) is proposed. According to the simulation results, by using the proposed method, the moving measurement data flow from an underground distributed mobile network can be acquired and transmitted efficiently.

  13. The GEOSS Science and Technology Stakeholder Network and Service Suite: Linking S&T Communities and GEOSS

    Science.gov (United States)

    Plag, Hans-Peter; Jules-Plag, Shelley

    2015-04-01

    The Global Earth Observation System of Systems (GEOSS) developed by the Group on Earth Observations (GEO) aims to provide practice-relevant knowledge in support of decision making in a wide range of societal benefit areas. Generating this practice-relevant knowledge based on Earth observations, socio-economic data and models often depends on research, and utilization of the societal benefits of EOs requires the involvement of science and research communities. Building a GEOSS responding to the needs of a wide range of users necessitates contributions from many science and technology (S&T) communities. In particular, a strong engagement of science and technology (S&T) communities in both the development and use of GEOSS is necessary to address the complex issues associated with the on-going transition out of the Holocene. S&T support is needed to improve interoperability between global observing, modeling, and information systems; to enable data integration across disciplinary boundaries; to facilitate data sharing, archiving, dissemination, and reanalysis; to optimize the recording of observations, assimilation of data into models, and generation of data products; to enhance the value of observations from individual observing systems through their integration in the SBAs; and to harmonize well-calibrated, highly accurate, stable, sustained in-situ and satellite observations of the same variable recorded by different sensors and different agencies. Consequently, the GEO Work Plan includes several Tasks focusing on outreach to S&T communities, and most of the GEO Community of Practice have a strong S&T component. The GEOSS S&T Stakeholder Network facilitates input from S&T communities to GEO. Infrastructure serving and linking S&T users communities and GEOSS has been developed and is integrated into a GEOSS S&T Service Suite (GSTSS). The GSTSS has several outreach components for the demonstration of GEOSS and its value for S&T communities, and for services supporting

  14. Reducing αENaC expression in kidney connecting tubule induces pseudohypoaldosteronism type 1 symptoms during K+ loading

    DEFF Research Database (Denmark)

    Poulsen, Søren Brandt; Praetorius, Jeppe; Damkier, Helle H

    2015-01-01

    Genetic inactivation of the epithelial Na(+) channel α-subunit (αENaC) in the renal collecting duct (CD) does not interfere with Na(+) and K(+) homeostasis in mice. However, inactivation in the CD and a part of the connecting tubule (CNT) induces autosomal recessive pseudohypoaldosteronism type 1...

  15. Diglycolic acid is the nephrotoxic metabolite in diethylene glycol poisoning inducing necrosis in human proximal tubule cells in vitro.

    Science.gov (United States)

    Landry, Greg M; Martin, Sarah; McMartin, Kenneth E

    2011-11-01

    Diethylene glycol (DEG), a solvent and chemical intermediate, can produce an acute toxic syndrome, the hallmark of which is acute renal failure due to cortical tubular degeneration and proximal tubular necrosis. DEG is metabolized to two primary metabolites, 2-hydroxyethoxyacetic acid (2-HEAA) and diglycolic acid (DGA), which are believed to be the proximate toxicants. The precise mechanism of toxicity has yet to be elucidated, so these studies were designed to determine which metabolite was responsible for the proximal tubule cell death. Human proximal tubule (HPT) cells in culture, obtained from normal cortical tissue and passaged 3-6 times, were incubated with increasing concentrations of DEG, 2-HEAA, or DGA separately and in combination for 48 h at pH 6 or 7.4, and various parameters of necrotic and apoptotic cell death were measured. DEG and 2-HEAA did not produce any cell death. DGA produced dose-dependent necrosis at concentrations above 25 mmol/l. DGA did not affect caspase-3 activity and increased annexin V staining only in propidium iodide-stained cells. Hence, DGA induced necrosis, not apoptosis, as corroborated by severe depletion of cellular adenosine triphosphate levels. DGA is structurally similar to citric acid cycle intermediates that are taken up by specific transporters in kidney cells. HPT cells, incubated with N-(p-amylcinnamoyl)anthranilic acid, a sodium dicarboxylate-1 transporter inhibitor showed significantly decreased cell death compared with DGA alone. These studies demonstrate that DGA is the toxic metabolite responsible for DEG-induced proximal tubular necrosis and suggest a possible transporter-mediated uptake of DGA leading to toxic accumulation and cellular dysfunction.

  16. Pb exposure attenuates hypersensitivity in vivo by increasing regulatory T cells

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Liang [Department of Immunology, Fourth Military Medical University, Xi' an 710032 (China); Zhao, Fang; Shen, Xuefeng [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Ouyang, Weiming [Laboratory of Cell Biology, Division of Monoclonal Antibodies, Office of Biotechnology Products, Center for Drug Evaluation and Research, United States Food and Drug Administration, Bethesda, MD (United States); Liu, Xinqin; Xu, Yan; Yu, Tao [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Jin, Boquan [Department of Immunology, Fourth Military Medical University, Xi' an 710032 (China); Chen, Jingyuan, E-mail: jy_chen@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Luo, Wenjing, E-mail: luowenj@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China)

    2012-12-01

    Pb is a common environmental pollutant affecting various organs. Exposure of the immune system to Pb leads to immunosuppression or immunodysregulation. Although previous studies showed that Pb exposure can modulate the function of helper T cells, Pb immunotoxicity remains incompletely understood. In this study, we investigated the effect of Pb exposure on T cell development, and the underlying mechanism of Pb-induced suppression of the delayed-type hypersensitivity (DTH) response in vivo. Sprague–Dawley rats were exposed to 300 ppm Pb-acetate solution via the drinking water for six weeks, and we found that Pb exposure significantly increased Pb concentrations in the blood by 4.2-fold (p < 0.05) as compared to those in the control rats. In Pb-exposed rats, the amount of thymic CD4{sup +}CD8{sup −} and peripheral CD4{sup +} T cells was significantly reduced, whereas, CD8{sup +} population was not affected. In contrast to conventional CD4{sup +} T cells, Foxp3{sup +} regulatory T cells (Tregs) were increased in both the thymus and peripheral lymphoid organs of Pb-exposed rats. In line with the increase of Tregs, the DTH response of Pb-exposed rats was markedly suppressed. Depletion of Tregs reversed the suppression of DTH response by Pb-exposed CD4{sup +} T cells in an adoptive transfer model, suggesting a critical role of the increased Tregs in suppressing the DTH response. Collectively, this study revealed that Pb-exposure may upregulate Tregs, thereby leading to immunosuppression. -- Highlights: ► Pb exposure impaired CD4{sup +} thymic T cell development. ► Peripheral T lymphocytes were reduced following Pb exposure. ► Pb exposure increases thymic and peripheral Treg cells in rats. ► Tregs played a critical role in Pb-exposure-induced immune suppression.

  17. Big Data Clustering via Community Detection and Hyperbolic Network Embedding in IoT Applications

    Directory of Open Access Journals (Sweden)

    Vasileios Karyotis

    2018-04-01

    Full Text Available In this paper, we present a novel data clustering framework for big sensory data produced by IoT applications. Based on a network representation of the relations among multi-dimensional data, data clustering is mapped to node clustering over the produced data graphs. To address the potential very large scale of such datasets/graphs that test the limits of state-of-the-art approaches, we map the problem of data clustering to a community detection one over the corresponding data graphs. Specifically, we propose a novel computational approach for enhancing the traditional Girvan–Newman (GN community detection algorithm via hyperbolic network embedding. The data dependency graph is embedded in the hyperbolic space via Rigel embedding, allowing more efficient computation of edge-betweenness centrality needed in the GN algorithm. This allows for more efficient clustering of the nodes of the data graph in terms of modularity, without sacrificing considerable accuracy. In order to study the operation of our approach with respect to enhancing GN community detection, we employ various representative types of artificial complex networks, such as scale-free, small-world and random geometric topologies, and frequently-employed benchmark datasets for demonstrating its efficacy in terms of data clustering via community detection. Furthermore, we provide a proof-of-concept evaluation by applying the proposed framework over multi-dimensional datasets obtained from an operational smart-city/building IoT infrastructure provided by the Federated Interoperable Semantic IoT/cloud Testbeds and Applications (FIESTA-IoT testbed federation. It is shown that the proposed framework can be indeed used for community detection/data clustering and exploited in various other IoT applications, such as performing more energy-efficient smart-city/building sensing.

  18. Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins.

    Science.gov (United States)

    Yalçın, Belgin; Zhao, Lu; Stofanko, Martin; O'Sullivan, Niamh C; Kang, Zi Han; Roost, Annika; Thomas, Matthew R; Zaessinger, Sophie; Blard, Olivier; Patto, Alex L; Sohail, Anood; Baena, Valentina; Terasaki, Mark; O'Kane, Cahir J

    2017-07-25

    Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought to be continuous with ER throughout the neuron; the mechanisms that form this axonal network are unknown. Mutations affecting reticulon or REEP proteins, with intramembrane hairpin domains that model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). We show that Drosophila axons have a dynamic axonal ER network, which these proteins help to model. Loss of HSP hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor axons, and occasional discontinuities in axonal ER. Ultrastructural analysis reveals an extensive ER network in axons, which shows larger and fewer tubules in larvae that lack reticulon and REEP proteins, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of axonal ER, thus suggesting roles for ER modeling in axon maintenance and function.

  19. Effect of ADH on rubidium transport in isolated perfused rat cortical collecting tubules

    International Nuclear Information System (INIS)

    Schafer, J.A.; Troutman, S.L.

    1986-01-01

    Unidirectional fluxes of 86Rb+ were measured as an indicator of potassium transport in isolated rat cortical collecting tubules perfused and bathed at 38 degrees C with isotonic solutions in which Rb+ replaced K+. Under control conditions the lumen-to-bath flux (Jl----b) was significantly less than the bath-to-lumen flux (Jb----l), indicating net Rb+ secretion. Net secretion increased approximately 180% after addition of 100 microU/ml of arginine vasopressin (ADH) to the bathing solution, due to a rapid and reversible increase in Jb----l from 4.6 +/- 0.8 to 9.0 +/- 1.9 pmol X min-1 X mm-1 with no significant change in Jl----b. The ADH effect was completely inhibited by 2 mM luminal Ba2+. The average transepithelial voltage (Ve) was not significantly different from zero in the control period but became lumen negative (-5 to -10 mV) after ADH. With 10(-5) M amiloride in the lumen Ve was lumen positive (+2 to +4 mV) and was unaltered by ADH or Ba2+, yet ADH produced a significant but attentuated increase in Jb----l with no change in Jl----b. The results indicate that ADH augments net K+ secretion either by an increase in the Ba2+-sensitive conductance of the apical membrane or by an increase in the electrochemical potential driving force for net Rb+ secretion through this pathway

  20. Internet of Things (IoT Based Design of a Secure and Lightweight Body Area Network (BAN Healthcare System

    Directory of Open Access Journals (Sweden)

    Yong-Yuan Deng

    2017-12-01

    Full Text Available As sensor networks and cloud computation technologies have rapidly developed over recent years, many services and applications integrating these technologies into daily life have come together as an Internet of Things (IoT. At the same time, aging populations have increased the need for expanded and more efficient elderly care services. Fortunately, elderly people can now wear sensing devices which relay data to a personal wireless device, forming a body area network (BAN. These personal wireless devices collect and integrate patients’ personal physiological data, and then transmit the data to the backend of the network for related diagnostics. However, a great deal of the information transmitted by such systems is sensitive data, and must therefore be subject to stringent security protocols. Protecting this data from unauthorized access is thus an important issue in IoT-related research. In regard to a cloud healthcare environment, scholars have proposed a secure mechanism to protect sensitive patient information. Their schemes provide a general architecture; however, these previous schemes still have some vulnerability, and thus cannot guarantee complete security. This paper proposes a secure and lightweight body-sensor network based on the Internet of Things for cloud healthcare environments, in order to address the vulnerabilities discovered in previous schemes. The proposed authentication mechanism is applied to a medical reader to provide a more comprehensive architecture while also providing mutual authentication, and guaranteeing data integrity, user untraceability, and forward and backward secrecy, in addition to being resistant to replay attack.

  1. The importance of including dynamic social networks when modeling epidemics of airborne infections: does increasing complexity increase accuracy?

    Science.gov (United States)

    Blower, Sally; Go, Myong-Hyun

    2011-07-19

    Mathematical models are useful tools for understanding and predicting epidemics. A recent innovative modeling study by Stehle and colleagues addressed the issue of how complex models need to be to ensure accuracy. The authors collected data on face-to-face contacts during a two-day conference. They then constructed a series of dynamic social contact networks, each of which was used to model an epidemic generated by a fast-spreading airborne pathogen. Intriguingly, Stehle and colleagues found that increasing model complexity did not always increase accuracy. Specifically, the most detailed contact network and a simplified version of this network generated very similar results. These results are extremely interesting and require further exploration to determine their generalizability.

  2. Top-down controls on bacterial community structure: microbial network analysis of bacteria, T4-like viruses and protists

    Science.gov (United States)

    Chow, Cheryl-Emiliane T; Kim, Diane Y; Sachdeva, Rohan; Caron, David A; Fuhrman, Jed A

    2014-01-01

    Characterizing ecological relationships between viruses, bacteria and protists in the ocean are critical to understanding ecosystem function, yet these relationships are infrequently investigated together. We evaluated these relationships through microbial association network analysis of samples collected approximately monthly from March 2008 to January 2011 in the surface ocean (0–5 m) at the San Pedro Ocean Time series station. Bacterial, T4-like myoviral and protistan communities were described by Automated Ribosomal Intergenic Spacer Analysis and terminal restriction fragment length polymorphism of the gene encoding the major capsid protein (g23) and 18S ribosomal DNA, respectively. Concurrent shifts in community structure suggested similar timing of responses to environmental and biological parameters. We linked T4-like myoviral, bacterial and protistan operational taxonomic units by local similarity correlations, which were then visualized as association networks. Network links (correlations) potentially represent synergistic and antagonistic relationships such as viral lysis, grazing, competition or other interactions. We found that virus–bacteria relationships were more cross-linked than protist–bacteria relationships, suggestive of increased taxonomic specificity in virus–bacteria relationships. We also found that 80% of bacterial–protist and 74% of bacterial–viral correlations were positive, with the latter suggesting that at monthly and seasonal timescales, viruses may be following their hosts more often than controlling host abundance. PMID:24196323

  3. Software defined access networks

    OpenAIRE

    Maricato, José Miguel Duarte

    2016-01-01

    With the increase of internet usage and the exponential growth of bandwidth consumption due to the increasing number of users of new generation equipments and the creation of new services that consume increasingly higher bandwidths, it's necessary to nd solutions to meet these new requirements. Passive optical networks (PONs) promise to solve these problems by providing a better service to users and providers. PON networks are very attractive since they don't depend on a...

  4. A low noise single-transistor transimpedance preamplifier for Fourier-transform mass spectrometry using a T feedback network.

    Science.gov (United States)

    Lin, Tzu-Yung; Green, Roger J; O'Connor, Peter B

    2012-09-01

    A novel single-transistor transimpedance preamplifier has been introduced for improving performance in Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry. A low noise junction field-effect transistor (JFET), BF862, is used as the main amplification stage of this trans-impedance preamplifier, and a T-shaped feedback network is introduced as both the feedback and the gate biasing solutions. The T feedback network has been studied using an operational amplifier (Op Amp), AD8099. Such a feedback system allows ~100-fold less feedback resistance at a given transimpedance, hence preserving bandwidth, which is beneficial to applications demanding high gain. The single-transistor preamplifier yields a tested transimpedance of ~10(4) Ω (80 dBΩ) in the frequency range between 1 kHz and 1 MHz (mass-to-charge ratio, m/z, of around 180-180k for a 12-T FT-ICR system), with a low power consumption of ~6 mW, which implies that this preamplifier is well suited to a 12-T FT-ICR mass spectrometer. In trading noise performance for higher trans-impedance, an alternative preamplifier design, an AD8099 preamplifier with the T feedback network, has also been studied with a capability of ~10(6) Ω (120 dBΩ) transimpedance in the same frequency range. The resistive components in the T feedback network reported here can be replaced by complex impedances, which allows adaptation of this feedback system to other frequency, transimpedance, and noise characteristics for applications not only in other mass spectrometers, such as Orbitrap, time-of-flight (TOF), and ion trap systems, but also in other charge/current detecting systems such as spectroscopy systems, microscopy systems, optical communication systems, or charge-coupled devices (CCDs).

  5. Meniscal T1rho and T2 measured with 3.0T MRI increases directly after running a marathon

    Energy Technology Data Exchange (ETDEWEB)

    Stehling, Christoph [University of California, Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); University of Muenster, Department of Clinical Radiology, Muenster (Germany); Luke, Anthony [University of California, Department of Orthopedic Surgery, San Francisco, CA (United States); Stahl, Robert [University of California, Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Ludwig Maximilians University of Munich, Department of Clinical Radiology, Munich (Germany); Baum, Thomas; Joseph, Gabby; Pan, Judong; Link, Thomas M. [University of California, Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, San Francisco, CA (United States)

    2011-06-15

    To prospectively evaluate changes in T1rho and T2 relaxation time in the meniscus using 3.0 T MRI in asymptomatic knees of marathon runners and to compare these findings with those of age-matched healthy subjects. Thirteen marathon runners underwent 3.0 T MRI including T1rho and T2 mapping sequences before, 48-72 h after, and 3 months after competition. Ten controls were examined at baseline and after 3 months. All images were analyzed by two musculoskeletal radiologists identifying and grading cartilage, meniscal, ligamentous. and other knee abnormalities with WORMS scores. Meniscal segmentation was performed to generate T1rho and T2 maps in six compartments. No differences in morphological knee abnormalities were found before and after the marathon. However, all marathon runners showed a significant increase in T1rho and T2 values after competition in all meniscus compartments (p < 0.0001), which may indicate changes in the biochemical composition of meniscal tissue. While T2 values decreased after 3 months T1rho values remained at a high level, indicating persisting changes in the meniscal matrix composition after a marathon. T2 values in menisci have the potential to be used as biomarkers for identifying reversible meniscus matrix changes indicating potential tissue damage. T1rho values need further study, but may be a valuable marker for diagnosing early, degenerative changes in the menisci following exercise. (orig.)

  6. 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...

  7. Changes in gene expression in human renal proximal tubule cells exposed to low concentrations of S-(1,2-dichlorovinyl)-L-cysteine, a metabolite of trichloroethylene

    International Nuclear Information System (INIS)

    Lock, Edward A.; Barth, Jeremy L.; Argraves, Scott W.; Schnellmann, Rick G.

    2006-01-01

    Epidemiology studies suggest that there may be a weak association between high level exposure to trichloroethylene (TCE) and renal tubule cell carcinoma. Laboratory animal studies have shown an increased incidence of renal tubule carcinoma in male rats but not mice. TCE can undergo metabolism via glutathione (GSH) conjugation to form metabolites that are known to be nephrotoxic. The GSH conjugate, S-(1,2-dichlorovinyl)glutathione (DCVG), is processed further to the cysteine conjugate, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), which is the penultimate nephrotoxic species. We have cultured human renal tubule cells (HRPTC) in serum-free medium under a variety of different culture conditions and observed growth, respiratory control and glucose transport over a 20 day period in medium containing low glucose. Cell death was time- and concentration-dependent, with the EC 5 for DCVG being about 3 μM and for DCVC about 7.5 μM over 10 days. Exposure of HRPTC to sub-cytotoxic doses of DCVC (0.1 μM and 1 μM for 10 days) led to a small number of changes in gene expression, as determined by transcript profiling with Affymetrix human genome chips. Using the criterion of a mean 2-fold change over control for the four samples examined, 3 genes at 0.1 μM DCVC increased, namely, adenosine kinase, zinc finger protein X-linked and an enzyme with lyase activity. At 1 μM DCVC, two genes showed a >2-fold decrease, N-acetyltransferase 8 and complement factor H. At a lower stringency (1.5-fold change), a total of 63 probe sets were altered at 0.1 μM DCVC and 45 at 1 μM DCVC. Genes associated with stress, apoptosis, cell proliferation and repair and DCVC metabolism were altered, as were a small number of genes that did not appear to be associated with the known mode of action of DCVC. Some of these genes may serve as molecular markers of TCE exposure and effects in the human kidney

  8. Capability-based Access Control Delegation Model on the Federated IoT Network

    DEFF Research Database (Denmark)

    Anggorojati, Bayu; Mahalle, Parikshit N.; Prasad, Neeli R.

    2012-01-01

    Flexibility is an important property for general access control system and especially in the Internet of Things (IoT), which can be achieved by access or authority delegation. Delegation mechanisms in access control that have been studied until now have been intended mainly for a system that has...... no resource constraint, such as a web-based system, which is not very suitable for a highly pervasive system such as IoT. To this end, this paper presents an access delegation method with security considerations based on Capability-based Context Aware Access Control (CCAAC) model intended for federated...... machine-to-machine communication or IoT networks. The main idea of our proposed model is that the access delegation is realized by means of a capability propagation mechanism, and incorporating the context information as well as secure capability propagation under federated IoT environments. By using...

  9. Visfatin Reduces Gap Junction Mediated Cell-to-Cell Communication in Proximal Tubule-Derived Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Claire E. Hills

    2013-11-01

    Full Text Available Background/Aims: In the current study we examined if the adipocytokine, visfatin, alters connexin-mediated intercellular communication in proximal tubule-derived epithelial cells. Methods: The effects of visfatin (10-200ng/mL on cell viability and cytotoxicity in HK2-cells were assessed by MTT, crystal violet and lactate dehydrogenase assays. Western blot analysis was used to confirm expression of Cx26, Cx40 and Cx43. The effect of visfatin (10-200ng/mL on TGF-β1 secretion was confirmed by ELISA, and the effects of both TGF-β1 (2-10ng/mL and visfatin (10-200ng/mL on connexin expression were assessed by western blot. Functional intercellular communication was determined using transfer of Lucifer Yellow and paired-whole cell patch clamp electrophysiology. Results: In low glucose (5mM, visfatin (10-200ng/mL did not affect membrane integrity, cytotoxicity or cell viability at 48hrs, but did evoke a concentration-dependent reduction in Cx26 and Cx43 expression. The expression of Cx40 was unaffected. At 48hrs, visfatin (10-200ng/mL increased the secretion of TGF-β1 and the visfatin-evoked changes in connexin expression were mimicked by exogenous application of the pro-fibrotic cytokine (2-10ng/ml. Visfatin reduced dye transfer between coupled cells and decreased functional conductance, with levels falling by 63% as compared to control. Although input resistance was increased following visfatin treatment by 166%, the change was not significant as compared to control. The effects of visfatin on Cx-expression and cell-coupling were blocked in the presence of a TGF-β1 specific neutralizing antibody. Conclusions: The adipocytokine visfatin selectively evoked a non-toxic reduction in connexin expression in HK2-cells. The loss in gap-junction associated proteins was mirrored by a loss in functional conductance between coupled cells. Visfatin increased TGF-β secretion and the pattern of change for connexins expression was mimicked by exogenous

  10. Observations of skeletal microstructures in various types of dust deposit in tokamak T-10

    International Nuclear Information System (INIS)

    Kolbasov, B.N.; Kukushkin, A.B.; Rantsev-Kartinov, V.A.; Romanov, P.V.

    2003-01-01

    An analysis of electron transmission and scanning micrographs of various types of dust deposit in tokamak T-10 was carried out for (a) analyzing the origin of non-trivial (e.g. cauliflower-like) structures in dust deposits in tokamaks, and (b) verifying the former hypothesis for the possibility of self-assembling, during electric breakdown, of skeletal macro structures from wildly formed carbon nano tubes. The results show (i) the presence of tubular structures in the range of diameters D ∼ 5 nm - 10 μm; (ii) the trend of assembling bigger tubules from smaller ones (i.e., the self-similarity); (iii) the ability of nano tubular structures to build up the skeletons of various topology, including the tubules, cartwheels, dendrites; (iv) the presence of an amorphous (mostly, hydrocarbon) component which may hide the internal skeleton either fully (to give a solitary dust particle, e.g. of submicron size) or partly (to give an agglomerate of visually separate particles); (v) the similarity of tubules and cartwheels in the dust deposits, in the range D < 10 μm, and in the (high temporal resolution) images of plasma in tokamaks, Z-pinches and plasma focus, D ∼ 5 nm - 100 μ - 10 cm. (author)

  11. Hexavalent chromium at low concentration alters Sertoli cell barrier and connexin 43 gap junction but not claudin-11 and N-cadherin in the rat seminiferous tubule culture model

    Energy Technology Data Exchange (ETDEWEB)

    Carette, Diane [INSERM U 1065, Team 5 “Physiopathology of Germ Cell Control: Genomic and Non Genomic Mechanisms” C3M, University of Nice Sophia Antipolis, Nice (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Perrard, Marie-Hélène, E-mail: marie-helene.durand@ens-lyon.fr [Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon I, CNRS, INRA, Ecole Normale Supérieure de Lyon, Lyon (France); Prisant, Nadia [University of Versailles/St Quentin-en-Yvelines (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Gilleron, Jérome; Pointis, Georges [INSERM U 1065, Team 5 “Physiopathology of Germ Cell Control: Genomic and Non Genomic Mechanisms” C3M, University of Nice Sophia Antipolis, Nice (France); Segretain, Dominique [University of Versailles/St Quentin-en-Yvelines (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Durand, Philippe [Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon I, CNRS, INRA, Ecole Normale Supérieure de Lyon, Lyon (France); Kallistem SAS Ecole Normale Supérieure de Lyon, Lyon (France)

    2013-04-01

    Exposure to toxic metals, specifically those belonging to the nonessential group leads to human health defects and among them reprotoxic effects. The mechanisms by which these metals produce their negative effects on spermatogenesis have not been fully elucidated. By using the Durand's validated seminiferous tubule culture model, which mimics the in vivo situation, we recently reported that concentrations of hexavalent chromium, reported in the literature to be closed to that found in the blood circulation of men, increase the number of germ cell cytogenetic abnormalities. Since this metal is also known to affect cellular junctions, we investigated, in the present study, its potential influence on the Sertoli cell barrier and on junctional proteins present at this level such as connexin 43, claudin-11 and N-cadherin. Cultured seminiferous tubules in bicameral chambers expressed the three junctional proteins and ZO-1 for at least 12 days. Exposure to low concentrations of chromium (10 μg/l) increased the trans-epithelial resistance without major changes of claudin-11 and N-cadherin expressions but strongly delocalized the gap junction protein connexin 43 from the membrane to the cytoplasm of Sertoli cells. The possibility that the hexavalent chromium-induced alteration of connexin 43 indirectly mediates the effect of the toxic metal on the blood–testis barrier dynamic is postulated. - Highlights: ► Influence of Cr(VI) on the Sertoli cell barrier and on junctional proteins ► Use of cultured seminiferous tubules in bicameral chambers ► Low concentrations of Cr(VI) (10 μg/l) altered the trans-epithelial resistance. ► Cr(VI) did not alter claudin-11 and N-cadherin. ► Cr(VI) delocalized connexin 43 from the membrane to the cytoplasm of Sertoli cells.

  12. Extensions of I{sub X}T{sub E}T and its application to electric power network supervision; Extensions d`I{sub X}T{sub E}t pour son application a la supervision d`un reseau electrique

    Energy Technology Data Exchange (ETDEWEB)

    Despouys, O.; Ingrand, F.; Ghallab, M.; Gouyon, J.P.

    1997-07-01

    A chronicle model describes a set of possible behaviours for a given dynamic system. I{sub X}T{sub E}T uses a reified logic and temporal constraints to describe chronicles. It also uses algorithms which allow it to recognize all the instances of theses chronicles through a stream of time-stamped events given as an input. I{sub X}T{sub E}T is used in a number of complex supervision applications. Recent extensions to I{sub X}T{sub E}T, enabling its application at the national utility Electricite de France for electric network supervision and more especially for event and fault diagnosis. The new approach, notably based on facultative events or non-events, is compared to the FONSYNT previous supervision approach used at EDF

  13. Adaptive regulation of taurine and beta-alanine uptake in a human kidney cell line from the proximal tubule

    DEFF Research Database (Denmark)

    Jessen, H; Jacobsen, Christian

    1997-01-01

    1. The underlying mechanisms involved in the adaptive regulation of beta-amino acid uptake in the human proximal tubule were examined by use of an immortalized human embryonic kidney epithelial cell line (IHKE). 2. The results indicated that the adaptive response to maintain whole-body taurine...

  14. Increasing penetration of renewable and distributed electricity generation and the need for different network regulation

    International Nuclear Information System (INIS)

    Joode, J. de; Jansen, J.C.; Welle, A.J. van der; Scheepers, M.J.J.

    2009-01-01

    The amount of decentralised electricity generation (DG) connected to distribution networks increases across EU member states. This increasing penetration of DG units poses potential costs and benefits for distribution system operators (DSOs). These DSOs are regulated since the business of electricity distribution is considered to be a natural monopoly. This paper identifies the impact of increasing DG penetration on the DSO business under varying parameters (network characteristics, DG technologies, network management type) and argues that current distribution network regulation needs to be improved in order for DSOs to continue to facilitate the integration of DG in the network. Several possible adaptations are analysed.

  15. Proximal Tubule Cell Hypothesis for Cardiorenal Syndrome in Diabetes

    Directory of Open Access Journals (Sweden)

    Akihiko Saito

    2011-01-01

    Full Text Available Incidence of cardiovascular disease (CVD is remarkably high among patients with chronic kidney disease (CKD, even in the early microalbuminuric stages with normal glomerular filtration rates. Proximal tubule cells (PTCs mediate metabolism and urinary excretion of vasculotoxic substances via apical and basolateral receptors and transporters. These cells also retrieve vasculoprotective substances from circulation or synthesize them for release into the circulation. PTCs are also involved in the uptake of sodium and phosphate, which are critical for hemodynamic regulation and maintaining the mineral balance, respectively. Dysregulation of PTC functions in CKD is likely to be associated with the development of CVD and is linked to the progression to end-stage renal disease. In particular, PTC dysfunction occurs early in diabetic nephropathy, a leading cause of CKD. It is therefore important to elucidate the mechanisms of PTC dysfunction to develop therapeutic strategies for treating cardiorenal syndrome in diabetes.

  16. Transport of salicylate in proximal tubule (S2 segment) isolated from rabbit kidney

    International Nuclear Information System (INIS)

    Schild, L.; Roch-Ramel, F.

    1988-01-01

    The secretory and the reabsorptive transport of salicylate was studied in the isolated and perfused rabbit proximal tubule (S 2 segment). Salicylate secretion (J sal b→l ) fulfilled the criteria for a carrier-mediated transport system: J sal b→l was saturable, was reversibly inhibited by probenecid, and occurred against a concentration gradient. The K m and V max for this secretory transport were 80 μM and 3,200 fmol·min -1 ·mm -1 , respectively. At luminal pH of 7.4 and 6.6, salicylate reabsorption (J sal l→b ) was low. J sal l→b was stimulated by increasing the bath Pco 2 or by removing basolateral HCO 3 - ; J sal l→b was inhibited by ethoxyzolamide and by SITS in the bath. The results indicate that salicylate reabsorption depends on H + secretion, consistent with reabsorption by simple nonionic diffusion. When salicylate was present in the lumen only, J sal l→b increased after inhibition of the secretory transport by adding ouabain or probenecid in the bath or by lowering the bath temperature. These results are compatible with luminal recycling of salicylate, and suggest the presence of a mediated secretory transporter located at the luminal membrane

  17. Caulimoviridae Tubule-Guided Transport Is Dictated by Movement Protein Properties ▿

    Science.gov (United States)

    Sánchez-Navarro, Jesús; Fajardo, Thor; Zicca, Stefania; Pallás, Vicente; Stavolone, Livia

    2010-01-01

    Plant viruses move through plasmodesmata (PD) either as nucleoprotein complexes (NPCs) or as tubule-guided encapsidated particles with the help of movement proteins (MPs). To explore how and why MPs specialize in one mechanism or the other, we tested the exchangeability of MPs encoded by DNA and RNA virus genomes by means of an engineered alfalfa mosaic virus (AMV) system. We show that Caulimoviridae (DNA genome virus) MPs are competent for RNA virus particle transport but are unable to mediate NPC movement, and we discuss this restriction in terms of the evolution of DNA virus MPs as a means of mediating DNA viral genome entry into the RNA-trafficking PD pathway. PMID:20130061

  18. Stimulation of Na+-alanine cotransport activates a voltage-dependent conductance in single proximal tubule cells isolated from frog kidney

    Science.gov (United States)

    Robson, L; Hunter, M

    1999-01-01

    The swelling induced by Na+-alanine cotransport in proximal tubule cells of the frog kidney is followed by regulatory volume decrease (RVD). This RVD is inhibited by gadolinium (Gd3+), an inhibitor of stretch-activated channels, but is independent of extracellular Ca2+. In this study, the whole cell patch clamp technique was utilized to examine the effect of Na+-alanine cotransport on two previously identified volume- and Gd3+-sensitive conductances. One conductance is voltage dependent and anion selective (GVD) whilst the other is voltage independent and cation selective (GVI). Addition of 5 mM L-alanine to the bathing solution increased the whole cell conductance and gave a positive (depolarizing) shift in the reversal potential (Vrev, equivalent to the membrane potential in current-clamped cells) consistent with activation of Na+-alanine cotransport. Vrev shifted from -36 ± 4·9 to +12·9 ± 4·2 mV (n= 15). In the presence of alanine, the total whole cell conductance had several components including the cotransporter conductance and GVD and GVI. These conductances were separated using Gd3+, which inhibits both GVD and GVI, and the time dependency of GVD. Of these two volume-sensitive conductances, L-alanine elicited a specific increase in GVD, whereas GVI was unaffected. The L-alanine-induced activation of GVD was significantly reduced when cells were incubated in a hypertonic bathing solution. In summary, in single proximal tubule cells isolated from frog kidney, on stimulation of Na+-alanine cotransport GVD is activated, while GVI is unaffected. Taken with other evidence, this suggests that GVD is activated by cell swelling, consequent upon alanine entry, and may play a role as an anion efflux pathway during alanine-induced volume regulation. PMID:10226159

  19. Localization of Secondary Metabolites in Marine Invertebrates: Contribution of MALDI MSI for the Study of Saponins in Cuvierian Tubules of H. forskali

    Science.gov (United States)

    Meriaux, Céline; Bonnel, David; Salzet, Michel; Fournier, Isabelle; Wisztorski, Maxence

    2010-01-01

    Background Several species of sea cucumbers of the family Holothuriidae possess a particular mechanical defense system called the Cuvierian tubules (Ct). It is also a chemical defense system as triterpene glycosides (saponins) appear to be particularly concentrated in Ct. In the present study, the precise localization of saponins in the Ct of Holothuria forskali is investigated. Classical histochemical labeling using lectin was firstly performed but did not generate any conclusive results. Thus, MALDI mass spectrometry Imaging (MALDI-MSI) was directly applied and completed by statistical multivariate tests. A comparison between the tubules of relaxed and stressed animals was realized. Results These analyses allowed the detection of three groups of ions, corresponding to the isomeric saponins of the tubules. Saponins detected at m/z 1287 and 1303 were the most abundant and were apparently localized in the connective tissue of the tubules of both relaxed and stressed individuals. Saponins at m/z 1125 and 1141 were detected in lower amount and were present in tissues of relaxed animals. Finally, saponin ions at 1433, 1449, 1463 and 1479 were observed in some Ct of stressed holothuroids in the outer part of the connective tissue. The saponin group m/z 14xx seems therefore to be stress-specific and could originate from modifications of the saponins with m/z of 11xx. Conclusions All the results taken together indicate a complex chemical defense mechanism with, for a single organ, different sets of saponins originating from different cell populations and presenting different responses to stress. The present study also reflects that MALDI-MSI is a valuable tool for chemical ecology studies in which specific chemical signalling molecules like allelochemicals or pheromones have to be tracked. This report represents one of the very first studies using these tools to provide a functional and ecological understanding of the role of natural products from marine invertebrates

  20. Proteomic-based insight into Malpighian tubules of silkworm Bombyx mori.

    Directory of Open Access Journals (Sweden)

    Xiao-wu Zhong

    Full Text Available Malpighian tubules (MTs are highly specific organs of arthropods (Insecta, Myriapoda and Arachnida for excretion and osmoregulation. In order to highlight the important genes and pathways involved in multi-functions of MTs, we performed a systematic proteomic analysis of silkworm MTs in the present work. Totally, 1,367 proteins were identified by one-dimensional gel electrophoresis coupled with liquid chromatography-tandem mass spectrometry, and as well as by Trans Proteomic Pipeline (TPP and Absolute protein expression (APEX analyses. Forty-one proteins were further identified by two-dimensional gel electrophoresis. Some proteins were revealed to be significantly associated with various metabolic processes, organic solute transport, detoxification and innate immunity. Our results might lay a good foundation for future functional studies of MTs in silkworm and other lepidoptera.

  1. A novel member of the trehalose transporter family functions as an H+-dependent trehalose transporter in the reabsorption of trehalose in Malpighian tubules.

    Directory of Open Access Journals (Sweden)

    Shingo eKikuta

    2012-07-01

    Full Text Available In insects, Malpighian tubules are functionally analogous to mammalian kidneys in that they not only are essential to excrete waste molecules into the lumen but also are responsible for the reabsorption of indispensable molecules, such as sugars, from the lumen to the principal cells. Among sugars, the disaccharide trehalose is highly important to insects because it is the main hemolymph sugar to serve as a source of energy and carbon. The trehalose transporter TRET1 participates in the transfer of newly synthesized trehalose from the fat body across the cellular membrane into the hemolymph. Although transport proteins must play a pivotal role in the reabsorption of trehalose in Malpighian tubules, the molecular context underlying this process remains obscure. Previously, we identified a Tret1 homolog (Nlst8 that is expressed principally in the Malpighian tubules of the brown planthopper (BPH. Here, we used the Xenopus oocyte expression system to show that NlST8 exerts trehalose transport activity that is elevated under low pH conditions. These functional assays indicate that Nlst8 encodes a proton-dependent trehalose transporter (H-TRET1. To examine the involvement of Nlst8 in trehalose reabsorption, we analyzed the sugar composition of honeydew by using BPH with RNAi gene silencing. Trehalose was detected in the honeydew as waste excreted from Nlst8-dsRNA-injected BPH under hyperglycemic conditions. However, trehalose was not expelled from GFP-dsRNA-injected BPH even under hyperglycemic conditions. We conclude that NlST8 could participate in trehalose reabsorption driven by a H+ gradient from the lumen to the principal cells of the Malpighian tubules.

  2. Feulgen-DNA response and chromatin condensation in Malpighian tubules of Melipona rufiventris and Melipona quadrifasciata (Hymenoptera, Apoidea).

    Science.gov (United States)

    Mampumbu, André Roberto; Mello, Maria Luiza S

    2008-08-01

    Melipona quadrifasciata and Melipona rufiventris are stingless bee species which present low and high heterochromatin content, respectively, on their mitotic chromosomes as assessed visually after a C-banding assay. However, these species do not show differences in the C-banding responses of their Malpighian tubule interphase nuclei. In the present study, the Feulgen-DNA response, which could inform on differences in DNA depurination due to differences in chromatin condensation, was compared in the cell nuclei of the Malpighian tubules of these species. It was hypothesized that differences in acid hydrolysis kinetics patterns, as assessed by Feulgen reaction and studied microspectrophotometrically, could discriminate M. quadrifasciata and M. rufiventris interphase nuclei not distinguishable with the C-banding method. Feulgen-DNA values corresponding to more than one ploidy class were found in both species; these values at the hydrolysis time corresponding to the maximal DNA depurination for each ploidy degree were higher in M. quadrifasciata, reflecting a higher DNA content in the Malpighian tubule cell nuclei of this species compared to those of M. rufiventris at the same larval instar. The maximal Feulgen-DNA values of M. quadrifasciata after short (50 min) and long (90 min) hydrolysis times were found to be closer to each other, while those of M. rufiventris occurred sharply at the long hydrolysis time, indicating that DNA depurination in M. quadrifasciata occurred faster. This result is probably related to the involvement of differences in chromatin condensation; it agrees with the idea that M. rufiventris contains more heterochromatin than M. quadrifasciata, which is supported by the analysis of results obtained with the image analysis parameter average absorption ratio. The depurination kinetics studied here with the Feulgen reaction were revealed to be more pertinent than the C-banding technique in establishing differences in levels of chromatin condensation

  3. The importance of including dynamic social networks when modeling epidemics of airborne infections: does increasing complexity increase accuracy?

    Directory of Open Access Journals (Sweden)

    Go Myong-Hyun

    2011-07-01

    Full Text Available Abstract Mathematical models are useful tools for understanding and predicting epidemics. A recent innovative modeling study by Stehle and colleagues addressed the issue of how complex models need to be to ensure accuracy. The authors collected data on face-to-face contacts during a two-day conference. They then constructed a series of dynamic social contact networks, each of which was used to model an epidemic generated by a fast-spreading airborne pathogen. Intriguingly, Stehle and colleagues found that increasing model complexity did not always increase accuracy. Specifically, the most detailed contact network and a simplified version of this network generated very similar results. These results are extremely interesting and require further exploration to determine their generalizability. Please see related article BMC Medicine, 2011, 9:87

  4. Accelerated recovery of renal mitochondrial and tubule homeostasis with SIRT1/PGC-1α activation following ischemia–reperfusion injury

    Energy Technology Data Exchange (ETDEWEB)

    Funk, Jason A., E-mail: funkj@musc.edu [Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Schnellmann, Rick G., E-mail: schnell@musc.edu [Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Ralph H. Johnson VA Medical Center, Charleston, SC 29401 (United States)

    2013-12-01

    Kidney ischemia–reperfusion (I/R) injury elicits cellular injury in the proximal tubule, and mitochondrial dysfunction is a pathological consequence of I/R. Promoting mitochondrial biogenesis (MB) as a repair mechanism after injury may offer a unique strategy to restore both mitochondrial and organ function. Rats subjected to bilateral renal pedicle ligation for 22 min were treated once daily with the SIRT1 activator SRT1720 (5 mg/kg) starting 24 h after reperfusion until 72 h–144 h. SIRT1 expression was elevated in the renal cortex of rats after I/R + vehicle treatment (IRV), but was associated with less nuclear localization. SIRT1 expression was even further augmented and nuclear localization was restored in the kidneys of rats after I/R + SRT1720 treatment (IRS). PGC-1α was elevated at 72 h–144 h in IRV and IRS kidneys; however, SRT1720 treatment induced deacetylation of PGC-1α, a marker of activation. Mitochondrial proteins ATP synthase β, COX I, and NDUFB8, as well as mitochondrial respiration, were diminished 24 h–144 h in IRV rats, but were partially or fully restored in IRS rats. Urinary kidney injury molecule-1 (KIM-1) was persistently elevated in both IRV and IRS rats; however, KIM-1 tissue expression was attenuated in IRS rats. Additionally, sustained loss of Na{sup +},K{sup +}–ATPase expression and basolateral localization and elevated vimentin in IRV rats was normalized in IRS rats, suggesting restoration of a differentiated, polarized tubule epithelium. The results suggest that SRT1720 treatment expedited recovery of mitochondrial protein expression and function by enhancing MB, which was associated with faster proximal tubule repair. Targeting MB may offer unique therapeutic strategy following ischemic injury. - Highlights: • We examined recovery of mitochondrial and renal function after ischemia–reperfusion. • SRT1720 treatment after I/R induced mitochondrial biogenesis via SIRT1/PGC-1α. • Recovery of mitochondrial function was

  5. The Influence of Concentration and Temperature on the Formation of ¿-Oryzanol + ß-Sitosterol Tubules in Edible Oil Organogels

    NARCIS (Netherlands)

    Sawalha, H.I.M.; Venema, P.; Bot, A.; Flöter, E.; Linden, van der E.

    2011-01-01

    The gelation process of mixtures of ¿-oryzanol and sitosterol structurants in sunflower oil was studied using light scattering, rheology, and micro-scanning calorimetry (Micro-DSC). The relation between temperature and the critical aggregation concentration (CAC) of tubule formation of ¿-oryzanol

  6. Effects of angiotensin II and ionomycin on fluid and bicarbonate absorption in the rat proximal tubule

    International Nuclear Information System (INIS)

    Chatsudthipong, V.; Chan, Y.L.

    1986-01-01

    Microperfusion of proximal convoluted tubule(PCT) and peritubular capillaries was performed to examine the effects of angiotensin II(Ang II) and ionomycin on fluid and bicarbonate absorption. Bicarbonate was determined by microcalorimetry and C-14 inulin was used as a volume marker. The rates of bicarbonate absorption (JHCO 3 ) was 143 peq/min x mm and fluid absorption(Jv) was 2.70 nl/min x mm, when PCT and capillary perfusate contained normal Ringer solution. Addition of Ang II (10 -6 M) to the capillary perfusate caused reductions of JHCO 3 and Jv by 35%. A similar effect was observed when ionomycin was added to the capillary perfusate. Ang II antagonist, (Sar 1 , Ile 8 )-Angiotensin II(10 -6 M), completely blocked the inhibitory effect of Ang II on Jv and JHCO 3 . Removal of calcium from both luminal and capillary perfusate did not change the effect of Ang II on Jv and JHCO 3 . Our results indicate that Ang II inhibits the sodium-hydrogen exchanger in the proximal tubule via interacting with angiotensin receptor. The mechanism of Ang II action may involve mobilization of intracellular calcium

  7. Magnetoencephalography Reveals a Widespread Increase in Network Connectivity in Idiopathic/Genetic Generalized Epilepsy.

    Directory of Open Access Journals (Sweden)

    Adham Elshahabi

    Full Text Available Idiopathic/genetic generalized epilepsy (IGE/GGE is characterized by seizures, which start and rapidly engage widely distributed networks, and result in symptoms such as absences, generalized myoclonic and primary generalized tonic-clonic seizures. Although routine magnetic resonance imaging is apparently normal, many studies have reported structural alterations in IGE/GGE patients using diffusion tensor imaging and voxel-based morphometry. Changes have also been reported in functional networks during generalized spike wave discharges. However, network function in the resting-state without epileptiforme discharges has been less well studied. We hypothesize that resting-state networks are more representative of the underlying pathophysiology and abnormal network synchrony. We studied functional network connectivity derived from whole-brain magnetoencephalography recordings in thirteen IGE/GGE and nineteen healthy controls. Using graph theoretical network analysis, we found a widespread increase in connectivity in patients compared to controls. These changes were most pronounced in the motor network, the mesio-frontal and temporal cortex. We did not, however, find any significant difference between the normalized clustering coefficients, indicating preserved gross network architecture. Our findings suggest that increased resting state connectivity could be an important factor for seizure spread and/or generation in IGE/GGE, and could serve as a biomarker for the disease.

  8. Renal protein synthesis in diabetes mellitus: effects of insulin and insulin-like growth factor I

    International Nuclear Information System (INIS)

    Barac-Nieto, M.; Lui, S.M.; Spitzer, A.

    1991-01-01

    Is increased synthesis of proteins responsible for the hypertrophy of kidney cells in diabetes mellitus? Does the lack of insulin, and/or the effect of insulin-like growth factor I (IGFI) on renal tubule protein synthesis play a role in diabetic renal hypertrophy? To answer these questions, we determined the rates of 3H-valine incorporation into tubule proteins and the valine-tRNA specific activity, in the presence or absence of insulin and/or IGFI, in proximal tubule suspension isolated from kidneys of streptozotocin diabetic and control rats. The rate of protein synthesis increased, while the stimulatory effects of insulin and IGFI on tubule protein synthesis were reduced, early (96 hours) after induction of experimental diabetes. Thus, hypertrophy of the kidneys in experimental diabetes mellitus is associated with increases in protein synthesis, rather than with decreases in protein degradation. Factor(s) other than the lack of insulin, or the effects of IGFI, must be responsible for the high rate of protein synthesis present in the hypertrophying tubules of diabetic rats

  9. Prediction-Based Energy Saving Mechanism in 3GPP NB-IoT Networks.

    Science.gov (United States)

    Lee, Jinseong; Lee, Jaiyong

    2017-09-01

    The current expansion of the Internet of things (IoT) demands improved communication platforms that support a wide area with low energy consumption. The 3rd Generation Partnership Project introduced narrowband IoT (NB-IoT) as IoT communication solutions. NB-IoT devices should be available for over 10 years without requiring a battery replacement. Thus, a low energy consumption is essential for the successful deployment of this technology. Given that a high amount of energy is consumed for radio transmission by the power amplifier, reducing the uplink transmission time is key to ensure a long lifespan of an IoT device. In this paper, we propose a prediction-based energy saving mechanism (PBESM) that is focused on enhanced uplink transmission. The mechanism consists of two parts: first, the network architecture that predicts the uplink packet occurrence through a deep packet inspection; second, an algorithm that predicts the processing delay and pre-assigns radio resources to enhance the scheduling request procedure. In this way, our mechanism reduces the number of random accesses and the energy consumed by radio transmission. Simulation results showed that the energy consumption using the proposed PBESM is reduced by up to 34% in comparison with that in the conventional NB-IoT method.

  10. The in vitro antibacterial effect of iodine-potassium iodide and calcium hydroxide in infected dentinal tubules at different time intervals.

    Science.gov (United States)

    Lin, Shaul; Kfir, Anda; Laviv, Amir; Sela, Galit; Fuss, Zvi

    2009-03-01

    The aim of this study was to evaluate the antibacterial effect of iodine-potassium iodide (IKI) and calcium hydroxide (CH) on dentinal tubules infected with Enterococcus faecalis (E. faecalis) at different time intervals. Hollow cylinders of bovine root dentin (n=45) were infected and divided into three equal groups filled with either IKI or CH and a positive control. After placing each medicament in the infected cylinders for time periods of 10 minutes, 48 hours and 7 days, microbiological samples were analyzed. At the end of each period, four 100 microm thick inner dentin layers (400 microm thick from each specimen) were removed using dental burs of increasing diameters. Dentin powder was cultured on agar plates to quantitatively assess their infection, expressed in colony forming units (cfu). In all layers of the positive control group, heavy bacterial infection was observed. After 10 minutes, IKI reduced the amount of viable bacteria more efficiently than CH, whereas at later time intervals CH showed the best results. For short periods of exposure, IKI has a more efficient antibacterial effect in the dentinal tubules than CH but CH performs better after longer durations of exposure. This research indicates the use of IKI is a better choice for disinfecting the root canal than CH if only a short duration of exposure is used because of its more efficient antibacterial effect. However, if a longer exposure time is used, then CH is a better choice because of its better disinfecting effect over time.

  11. A Network Coverage Information-Based Sensor Registry System for IoT Environments.

    Science.gov (United States)

    Jung, Hyunjun; Jeong, Dongwon; Lee, Sukhoon; On, Byung-Won; Baik, Doo-Kwon

    2016-07-25

    The Internet of Things (IoT) is expected to provide better services through the interaction of physical objects via the Internet. However, its limitations cause an interoperability problem when the sensed data are exchanged between the sensor nodes in wireless sensor networks (WSNs), which constitute the core infrastructure of the IoT. To address this problem, a Sensor Registry System (SRS) is used. By using a SRS, the information of the heterogeneous sensed data remains pure. If users move along a road, their mobile devices predict their next positions and obtain the sensed data for that position from the SRS. If the WSNs in the location in which the users move are unstable, the sensed data will be lost. Consider a situation where the user passes through dangerous areas. If the user's mobile device cannot receive information, they cannot be warned about the dangerous situation. To avoid this, two novel SRSs that use network coverage information have been proposed: one uses OpenSignal and the other uses the probabilistic distribution of the users accessing SRS. The empirical study showed that the proposed method can seamlessly provide services related to sensing data under any abnormal circumstance.

  12. Increased signaling entropy in cancer requires the scale-free property of protein interaction networks

    Science.gov (United States)

    Teschendorff, Andrew E.; Banerji, Christopher R. S.; Severini, Simone; Kuehn, Reimer; Sollich, Peter

    2015-01-01

    One of the key characteristics of cancer cells is an increased phenotypic plasticity, driven by underlying genetic and epigenetic perturbations. However, at a systems-level it is unclear how these perturbations give rise to the observed increased plasticity. Elucidating such systems-level principles is key for an improved understanding of cancer. Recently, it has been shown that signaling entropy, an overall measure of signaling pathway promiscuity, and computable from integrating a sample's gene expression profile with a protein interaction network, correlates with phenotypic plasticity and is increased in cancer compared to normal tissue. Here we develop a computational framework for studying the effects of network perturbations on signaling entropy. We demonstrate that the increased signaling entropy of cancer is driven by two factors: (i) the scale-free (or near scale-free) topology of the interaction network, and (ii) a subtle positive correlation between differential gene expression and node connectivity. Indeed, we show that if protein interaction networks were random graphs, described by Poisson degree distributions, that cancer would generally not exhibit an increased signaling entropy. In summary, this work exposes a deep connection between cancer, signaling entropy and interaction network topology. PMID:25919796

  13. Genetic effect of interleukin-1 beta (C-511T) polymorphism on the structural covariance network and white matter integrity in Alzheimer's disease.

    Science.gov (United States)

    Huang, Chi-Wei; Hsu, Shih-Wei; Tsai, Shih-Jen; Chen, Nai-Ching; Liu, Mu-En; Lee, Chen-Chang; Huang, Shu-Hua; Chang, Weng-Neng; Chang, Ya-Ting; Tsai, Wan-Chen; Chang, Chiung-Chih

    2017-01-18

    Inflammatory processes play a pivotal role in the degenerative process of Alzheimer's disease. In humans, a biallelic (C/T) polymorphism in the promoter region (position-511) (rs16944) of the interleukin-1 beta gene has been significantly associated with differences in the secretory capacity of interleukin-1 beta. In this study, we investigated whether this functional polymorphism mediates the brain networks in patients with Alzheimer's disease. We enrolled a total of 135 patients with Alzheimer's disease (65 males, 70 females), and investigated their gray matter structural covariance networks using 3D T1 magnetic resonance imaging and their white matter macro-structural integrities using fractional anisotropy. The patients were classified into two genotype groups: C-carriers (n = 108) and TT-carriers (n = 27), and the structural covariance networks were constructed using seed-based analysis focusing on the default mode network medial temporal or dorsal medial subsystem, salience network and executive control network. Neurobehavioral scores were used as the major outcome factors for clinical correlations. There were no differences between the two genotype groups in the cognitive test scores, seed, or peak cluster volumes and white matter fractional anisotropy. The covariance strength showing C-carriers > TT-carriers was the entorhinal-cingulum axis. There were two peak clusters (Brodmann 6 and 10) in the salience network and four peak clusters (superior prefrontal, precentral, fusiform, and temporal) in the executive control network that showed C-carriers covariance strength. The salience network and executive control network peak clusters in the TT group and the default mode network peak clusters in the C-carriers strongly predicted the cognitive test scores. Interleukin-1 beta C-511 T polymorphism modulates the structural covariance strength on the anterior brain network and entorhinal-interconnected network which were independent of the white

  14. A microfluidic renal proximal tubule with active reabsorptive function.

    Directory of Open Access Journals (Sweden)

    Else M Vedula

    Full Text Available In the kidney, the renal proximal tubule (PT reabsorbs solutes into the peritubular capillaries through active transport. Here, we replicate this reabsorptive function in vitro by engineering a microfluidic PT. The microfluidic PT architecture comprises a porous membrane with user-defined submicron surface topography separating two microchannels representing a PT filtrate lumen and a peritubular capillary lumen. Human PT epithelial cells and microvascular endothelial cells in respective microchannels created a PT-like reabsorptive barrier. Co-culturing epithelial and endothelial cells in the microfluidic architecture enhanced viability, metabolic activity, and compactness of the epithelial layer. The resulting tissue expressed tight junctions, kidney-specific morphology, and polarized expression of kidney markers. The microfluidic PT actively performed sodium-coupled glucose transport, which could be modulated by administration of a sodium-transport inhibiting drug. The microfluidic PT reproduces human physiology at the cellular and tissue levels, and measurable tissue function which can quantify kidney pharmaceutical efficacy and toxicity.

  15. Na sup + -K sup + -ATPase-dependent sodium flux in cortical collecting tubule

    Energy Technology Data Exchange (ETDEWEB)

    Blot-Chabaud, M.; Jaisser, F.; Gingold, M.; Bonvalet, J.P.; Farman, N. (CEntre d' Etudes Nucleaires de Saclay, Gif sur Yvette (France))

    1988-10-01

    The instantaneous rate of efflux of intracellular Na was studied in rabbit isolated cortical collecting tubules (CCT) as a function of temperature and intracellular Na concentration ((Na){sub i}). (Na){sub i} of microdissected CCT was increased by cold and K-free exposure in the presence of {sup 22}Na and the extracellular tracer ({sup 3}H)sorbitol. (Na){sub i} rose rapidly to 40 mM at 30 min, after which it rose more slowly, reaching 120-140 mM at 6 h. Kinetics of Na efflux were studied after rapid rewarming, using a special device allowing measurements at 20-s intervals. Under control conditions, the total Na load was extruded in <8 min, whereas, in the presence of 10{sup {minus}4} M ouabain, only 50% of the load was extruded during this period of time. Ouabain-sensitive Na efflux was first evident at 13{degree}C and gradually increased between 13 and 35{degree}C. At 37{degree}C, Na{sup +}-K{sup +}-ATPase-dependent Na efflux was dependent on (Na){sub i}. This efflux gradually increased, from 0.05 to 0.5 peq{center dot}nl tubular volume{sup {minus}1}{center dot}s{sup {minus}1} as a function of (Na){sub i} and reached a plateau at 70 mM (Na){sub i}. It is concluded that (Na){sub i} is a major modulator of the pump activity in CCT; at normal levels of (Na){sub i}, the pump is operating at only a small fraction of its total capacity.

  16. Increased T-helper 17 cell differentiation mediated by exosome-mediated microRNA-451 redistribution in gastric cancer infiltrated T cells.

    Science.gov (United States)

    Liu, Feng; Bu, Zhouyan; Zhao, Feng; Xiao, Daping

    2018-01-01

    MicroRNA (miR)-451 is a cell metabolism-related miRNA that can mediate cell energy-consuming models by several targets. As miR-451 can promote mechanistic target of rapamycin (mTOR) activity, and increased mTOR activity is related to increased differentiation of T-helper 17 (Th17) cells, we sought to investigate whether miR-451 can redistribute from cancer cells to infiltrated T cells and enhance the distribution of Th17 cells through mTOR. Real-time PCR was used for detecting expression of miR-451 in gastric cancer, tumor infiltrated T cells and exosomes, and distribution of Th17 was evaluated by both flow cytometry and immunohistochemistry (IHC). Immunofluorescence staining was used in monitoring the exosome-enveloped miR-451 from cancer cells to T cells with different treatments, and signaling pathway change was analyzed by western blot. miR-451 decreased significantly in gastric cancer (GC) tissues but increased in infiltrated T cells and exosomes; tumor miR-451 was negatively related to infiltrated T cells and exosome miR-451. Exosome miR-451 can not only serve as an indicator for poor prognosis of post-operation GC patients but is also related to increased Th17 distribution in gastric cancer. miR-451 can redistribute from cancer cells to T cells with low glucose treatment. Decreased 5' AMP-activated protein kinase (AMPK) and increased mTOR activity was investigated in miR-451 redistributed T cells and the Th17 polarized differentiation of these T cells were also increased. Exosome miR-451 derived from tumor tissues can serve as an indicator for poor prognosis and redistribution of miR-451 from cancer cells to infiltrated T cells in low glucose treatment can enhance Th17 differentiation by enhancing mTOR activity. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  17. De novo expression of sodium-glucose cotransporter SGLT2 in Bowman's capsule coincides with replacement of parietal epithelial cell layer with proximal tubule-like epithelium.

    Science.gov (United States)

    Tabatabai, Niloofar M; North, Paula E; Regner, Kevin R; Kumar, Suresh N; Duris, Christine B; Blodgett, Amy B

    2014-08-01

    In kidney nephron, parietal epithelial cells line the Bowman's capsule and function as a permeability barrier for the glomerular filtrate. Bowman's capsule cells with proximal tubule epithelial morphology have been found. However, the effects of tubular metaplasia in Bowman's capsule on kidney function remain poorly understood. Sodium-glucose cotransporter 2 (SGLT2) plays a major role in reabsorption of glucose in the kidney and is expressed on brush border membrane (BBM) of epithelial cells in the early segment of the proximal tubule. We hypothesized that SGLT2 is expressed in tubularized Bowman's capsule and used our novel antibody to test this hypothesis. Immunohistochemical analysis was performed with our SGLT2 antibody on C57BL/6 mouse kidney prone to have tubularized Bowman's capsules. Cell membrane was examined with periodic acid-Schiff (PAS) stain. The results showed that SGLT2 was localized on BBM of the proximal tubules in young and adult mice. Bowman's capsules were lined mostly with normal brush border-less parietal epithelial cells in young mice, while they were almost completely covered with proximal tubule-like cells in adult mice. Regardless of age, SGLT2 was expressed on BBM of the tubularized Bowman's capsule but did not co-localize with nephrin in the glomerulus. SGLT2-expressing tubular cells expanded from the urinary pole toward the vascular pole of the Bowman's capsule. This study identified the localization of SGLT2 in the Bowman's capsule. Bowman's capsules with tubular metaplasia may acquire roles in reabsorption of filtered glucose and sodium.

  18. Self-organization of engineered epithelial tubules by differential cellular motility

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Hidetoshi; Gjorevski, Nikolce; Inman, Jamie L; Bissell, Mina J; Nelson, Celeste M

    2009-02-04

    Patterning of developing tissues arises from a number of mechanisms, including cell shape change, cell proliferation, and cell sorting from differential cohesion or tension. Here, we reveal that differences in cell motility can also lead to cell sorting within tissues. Using mosaic engineered mammary epithelial tubules, we found that cells sorted depending on their expression level of the membrane-anchored collagenase matrix metalloproteinase (MMP)-14. These rearrangements were independent of the catalytic activity of MMP14 but absolutely required the hemopexin domain. We describe a signaling cascade downstream of MMP14 through Rho kinase that allows cells to sort within the model tissues. Cell speed and persistence time were enhanced by MMP14 expression, but only the latter motility parameter was required for sorting. These results indicate that differential directional persistence can give rise to patterns within model developing tissues.

  19. Network Capacity Assessment and Increase in Systems with Intermittent Water Supply

    Directory of Open Access Journals (Sweden)

    Amilkar E. Ilaya-Ayza

    2016-03-01

    Full Text Available Water supply systems have been facing many challenges in recent decades due to the potential effects of climate change and rapid population growth. Water systems need to expand because of demographic growth. Therefore, evaluating and increasing system capacity is crucial. Specifically, we analyze network capacity as one of the main features of a system. When the network capacity starts to decrease, there is a risk that continuous supply will become intermittent. This paper discusses how network expansion carried out throughout the network life span typically reduces network capacity, thus transforming a system originally designed to work with continuous supply into a system with intermittent supply. A method is proposed to expand the network capacity in an environment of economic scarcity through a greedy algorithm that enables the definition of a schedule for pipe modification stages, and thus efficiently expands the network capacity. This method is, at the same time, an important step in the process of changing a water system from intermittent back to continuous supply—an achievement that remains one of the main challenges related to water and health in developing countries.

  20. Personalized Social Network Activity Feeds for Increased Interaction and Content Contribution

    Directory of Open Access Journals (Sweden)

    Shlomo eBerkovsky

    2015-10-01

    Full Text Available Online social networks were originally conceived as means of sharing information and activities with friends, and their success has been one of the primary contributors of the tremendous growth of the Web. Social network activity feeds were devised as a means to aggregate recent actions of friends into a convenient list. But the volume of actions and content generated by social network users is overwhelming, such that keeping users up-to-date with friend activities is an ongoing challenge for social network providers. Personalization has been proposed as a solution to combat social network information overload and help users to identify the nuggets of relevant information in the incoming flood of network activities. In this paper, we propose and thoroughly evaluate a personalized model for predicting the relevance of the activity feed items, which informs the ranking of the feeds and facilitates personalization. Results of a live study show that the proposed feed personalization approach successfully identifies and promotes relevant feed items and boosts the uptake of the feeds. In addition, it increases the contribution of user-generated content to the social network and spurs interaction between users.

  1. Viewing socio-affective stimuli increases connectivity within an extended default mode network.

    Science.gov (United States)

    Göttlich, Martin; Ye, Zheng; Rodriguez-Fornells, Antoni; Münte, Thomas F; Krämer, Ulrike M

    2017-03-01

    Empathy is an essential ability for prosocial behavior. Previous imaging studies identified a number of brain regions implicated in affective and cognitive aspects of empathy. In this study, we investigated the neural correlates of empathy from a network perspective using graph theory and beta-series correlations. Two independent data sets were acquired using the same paradigm that elicited empathic responses to socio-affective stimuli. One data set was used to define the network nodes and modular structure, the other data set was used to investigate the effects of emotional versus neutral stimuli on network connectivity. Emotional relative to neutral stimuli increased connectivity between 74 nodes belonging to different networks. Most of these nodes belonged to an extended default mode network (eDMN). The other nodes belonged to a cognitive control network or visual networks. Within the eDMN, posterior STG/TPJ regions were identified as provincial hubs. The eDMN also showed stronger connectivity to the cognitive control network encompassing lateral PFC regions. Connector hubs between the two networks were posterior cingulate cortex and ventrolateral PFC. This stresses the advantage of a network approach as regions similarly modulated by task conditions can be dissociated into distinct networks and regions crucial for network integration can be identified. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Sulfatide-Reactive Natural Killer T Cells Abrogate Ischemia-Reperfusion Injury

    OpenAIRE

    Yang, Seung Hee; Lee, Jung Pyo; Jang, Hye Ryoun; Cha, Ran-hui; Han, Seung Seok; Jeon, Un Sil; Kim, Dong Ki; Song, Junghan; Lee, Dong-Sup; Kim, Yon Su

    2011-01-01

    There is a significant immune response to ischemia-reperfusion injury (IRI), but the role of immunomodulatory natural killer T (NKT) cell subtypes is not well understood. Here, we compared the severity of IRI in mice deficient in type I/II NKT cells (CD1d−/−) or type I NKT cells (Jα18−/−). The absence of NKT cells, especially type II NKT cells, accentuated the severity of renal injury, whereas repletion of NKT cells attenuated injury. Adoptively transferred NKT cells trafficked into the tubul...

  3. Networking for philanthropy: increasing volunteer behavior via social networking sites.

    Science.gov (United States)

    Kim, Yoojung; Lee, Wei-Na

    2014-03-01

    Social networking sites (SNSs) provide a unique social venue to engage the young generation in philanthropy through their networking capabilities. An integrated model that incorporates social capital into the Theory of Reasoned Action is developed to explain volunteer behavior through social networks. As expected, volunteer behavior was predicted by volunteer intention, which was influenced by attitudes and subjective norms. In addition, social capital, an outcome of the extensive use of SNSs, was as an important driver of users' attitude and subjective norms toward volunteering via SNSs.

  4. A Novel Secure IoT-Based Smart Home Automation System Using a Wireless Sensor Network

    Science.gov (United States)

    Pirbhulal, Sandeep; Zhang, Heye; E Alahi, Md Eshrat; Ghayvat, Hemant; Mukhopadhyay, Subhas Chandra; Zhang, Yuan-Ting; Wu, Wanqing

    2016-01-01

    Wireless sensor networks (WSNs) provide noteworthy benefits over traditional approaches for several applications, including smart homes, healthcare, environmental monitoring, and homeland security. WSNs are integrated with the Internet Protocol (IP) to develop the Internet of Things (IoT) for connecting everyday life objects to the internet. Hence, major challenges of WSNs include: (i) how to efficiently utilize small size and low-power nodes to implement security during data transmission among several sensor nodes; (ii) how to resolve security issues associated with the harsh and complex environmental conditions during data transmission over a long coverage range. In this study, a secure IoT-based smart home automation system was developed. To facilitate energy-efficient data encryption, a method namely Triangle Based Security Algorithm (TBSA) based on efficient key generation mechanism was proposed. The proposed TBSA in integration of the low power Wi-Fi were included in WSNs with the Internet to develop a novel IoT-based smart home which could provide secure data transmission among several associated sensor nodes in the network over a long converge range. The developed IoT based system has outstanding performance by fulfilling all the necessary security requirements. The experimental results showed that the proposed TBSA algorithm consumed less energy in comparison with some existing methods. PMID:28042831

  5. A Novel Secure IoT-Based Smart Home Automation System Using a Wireless Sensor Network.

    Science.gov (United States)

    Pirbhulal, Sandeep; Zhang, Heye; E Alahi, Md Eshrat; Ghayvat, Hemant; Mukhopadhyay, Subhas Chandra; Zhang, Yuan-Ting; Wu, Wanqing

    2016-12-30

    Wireless sensor networks (WSNs) provide noteworthy benefits over traditional approaches for several applications, including smart homes, healthcare, environmental monitoring, and homeland security. WSNs are integrated with the Internet Protocol (IP) to develop the Internet of Things (IoT) for connecting everyday life objects to the internet. Hence, major challenges of WSNs include: (i) how to efficiently utilize small size and low-power nodes to implement security during data transmission among several sensor nodes; (ii) how to resolve security issues associated with the harsh and complex environmental conditions during data transmission over a long coverage range. In this study, a secure IoT-based smart home automation system was developed. To facilitate energy-efficient data encryption, a method namely Triangle Based Security Algorithm (TBSA) based on efficient key generation mechanism was proposed. The proposed TBSA in integration of the low power Wi-Fi were included in WSNs with the Internet to develop a novel IoT-based smart home which could provide secure data transmission among several associated sensor nodes in the network over a long converge range. The developed IoT based system has outstanding performance by fulfilling all the necessary security requirements. The experimental results showed that the proposed TBSA algorithm consumed less energy in comparison with some existing methods.

  6. A Novel Secure IoT-Based Smart Home Automation System Using a Wireless Sensor Network

    Directory of Open Access Journals (Sweden)

    Sandeep Pirbhulal

    2016-12-01

    Full Text Available Wireless sensor networks (WSNs provide noteworthy benefits over traditional approaches for several applications, including smart homes, healthcare, environmental monitoring, and homeland security. WSNs are integrated with the Internet Protocol (IP to develop the Internet of Things (IoT for connecting everyday life objects to the internet. Hence, major challenges of WSNs include: (i how to efficiently utilize small size and low-power nodes to implement security during data transmission among several sensor nodes; (ii how to resolve security issues associated with the harsh and complex environmental conditions during data transmission over a long coverage range. In this study, a secure IoT-based smart home automation system was developed. To facilitate energy-efficient data encryption, a method namely Triangle Based Security Algorithm (TBSA based on efficient key generation mechanism was proposed. The proposed TBSA in integration of the low power Wi-Fi were included in WSNs with the Internet to develop a novel IoT-based smart home which could provide secure data transmission among several associated sensor nodes in the network over a long converge range. The developed IoT based system has outstanding performance by fulfilling all the necessary security requirements. The experimental results showed that the proposed TBSA algorithm consumed less energy in comparison with some existing methods.

  7. Receptor-mediated endocytosis of lysozyme in renal proximal tubules of the frog Rana temporaria

    Directory of Open Access Journals (Sweden)

    E.V. Seliverstova

    2015-04-01

    Full Text Available The mechanism of protein reabsorption in the kidney of lower vertebrates remains insufficiently investigated in spite of raising interest to the amphibian and fish kidneys as a useful model for physiological and pathophysiological examinations. In the present study, we examined the renal tubular uptake and the internalization rote of lysozyme after its intravenous injection in the wintering frog Rana temporaria using immunohisto- and immunocytochemistry and specific markers for some endocytic compartments. The distinct expression of megalin and cubilin in the proximal tubule cells of lysozyme-injected frogs was revealed whereas kidney tissue of control animals showed no positive immunoreactivity. Lysozyme was detected in the apical endocytic compartment of the tubular cells and colocalized with clathrin 10 min after injection. After 20 min, lysozyme was located in the subapical compartment negative to clathrin (endosomes, and intracellular trafficking of lysozyme was coincided with the distribution of megalin and cubilin. However, internalized protein was retained in the endosomes and did not reach lysosomes within 30 min after treatment that may indicate the inhibition of intracellular trafficking in hibernating frogs. For the first time, we provided the evidence that lysozyme is filtered through the glomeruli and absorbed by receptor-mediated clathrin-dependent endocytosis in the frog proximal tubule cells. Thus, the protein uptake in the amphibian mesonephros is mediated by megalin and cubilin that confirms a critical role of endocytic receptors in the renal reabsorption of proteins in amphibians as in mammals.

  8. Superresolution microscope image reconstruction by spatiotemporal object decomposition and association: application in resolving t-tubule structure in skeletal muscle.

    Science.gov (United States)

    Sun, Mingzhai; Huang, Jiaqing; Bunyak, Filiz; Gumpper, Kristyn; De, Gejing; Sermersheim, Matthew; Liu, George; Lin, Pei-Hui; Palaniappan, Kannappan; Ma, Jianjie

    2014-05-19

    One key factor that limits resolution of single-molecule superresolution microscopy relates to the localization accuracy of the activated emitters, which is usually deteriorated by two factors. One originates from the background noise due to out-of-focus signals, sample auto-fluorescence, and camera acquisition noise; and the other is due to the low photon count of emitters at a single frame. With fast acquisition rate, the activated emitters can last multiple frames before they transiently switch off or permanently bleach. Effectively incorporating the temporal information of these emitters is critical to improve the spatial resolution. However, majority of the existing reconstruction algorithms locate the emitters frame by frame, discarding or underusing the temporal information. Here we present a new image reconstruction algorithm based on tracklets, short trajectories of the same objects. We improve the localization accuracy by associating the same emitters from multiple frames to form tracklets and by aggregating signals to enhance the signal to noise ratio. We also introduce a weighted mean-shift algorithm (WMS) to automatically detect the number of modes (emitters) in overlapping regions of tracklets so that not only well-separated single emitters but also individual emitters within multi-emitter groups can be identified and tracked. In combination with a maximum likelihood estimator method (MLE), we are able to resolve low to medium density of overlapping emitters with improved localization accuracy. We evaluate the performance of our method with both synthetic and experimental data, and show that the tracklet-based reconstruction is superior in localization accuracy, particularly for weak signals embedded in a strong background. Using this method, for the first time, we resolve the transverse tubule structure of the mammalian skeletal muscle.

  9. The single kinin receptor signals to separate and independent physiological pathways in Malpighian tubules of the yellow fever mosquito

    Science.gov (United States)

    In the past we have used the leucokinins, the kinins of the cockroach Leucophaea, to evaluate the mechanism of diuretic action of kinin peptides in Malpighian tubules of the yellow fever mosquito Aedes aegypti. Now using aedeskinins, the kinins of Aedes, are available, we find that in isolated Aede...

  10. Effect of a novel bioactive glass-ceramic on dentinal tubule occlusion: an in vitro study.

    Science.gov (United States)

    Zhong, Y; Liu, J; Li, X; Yin, W; He, T; Hu, D; Liao, Y; Yao, X; Wang, Y

    2015-03-01

    This in vitro study aimed to assess the ability and efficacy of HX-BGC, a novel bioactive glass-ceramic (SiO2-P2 O5-CaO-Na2 O-SrO), to reduce dentine tubule permeability. Dentine discs from human third molars were etched and randomly allocated into five groups: Group 1--distilled water; Group 2--Sensodyne Repair toothpaste (containing NovaMin®); Group 3--HX-BGC toothpaste (containing 7.5% HX-BGC); Group 4--control toothpaste (without HX-BGC); and Group 5--HX-BGC powder. Specimens were treated daily by brushing with an electric toothbrush for 20 seconds. Between daily treatments (7 days total), specimens were immersed in artificial saliva for 24 hours. Dentine permeability was measured at baseline, after the first treatment, after the first 24-hour immersion in artificial saliva and at the end of day 7. Dentine morphology and surface deposits were observed by scanning electron microscopy after one day and 7 days of treatment, respectively. Sensodyne Repair and bioactive glass-ceramic toothpaste significantly and immediately lowered dentine permeability. The HX-BGC powder group showed the highest reduction in dentine permeability after 7 days of treatment. The novel bioactive glass-ceramic material HX-BGC is effective in reducing dentine permeability by occluding open dentine tubules, indicating that HX-BGC may be a potential treatment for dentine hypersensitivity. © 2015 Australian Dental Association.

  11. Different Densities of Na-Ca Exchange Current in T-Tubular and Surface Membranes and Their Impact on Cellular Activity in a Model of Rat Ventricular Cardiomyocyte

    Czech Academy of Sciences Publication Activity Database

    Pásek, Michal; Šimurda, J.; Christé, G.

    2017-01-01

    Roč. 2017, č. 2017 (2017), č. článku 6343821. ISSN 2314-6133 Institutional support: RVO:61388998 Keywords : rat ventricular cell * mathematical model * Na-Ca current * t-tubules Subject RIV: BO - Biophysics OBOR OECD: Biophysics Impact factor: 2.476, year: 2016

  12. Regulation of transport in the connecting tubule and cortical collecting duct

    Science.gov (United States)

    Staruschenko, Alexander

    2012-01-01

    The central goal of this overview article is to summarize recent findings in renal epithelial transport, focusing chiefly on the connecting tubule (CNT) and the cortical collecting duct (CCD). Mammalian CCD and CNT are involved in fine tuning of electrolyte and fluid balance through reabsorption and secretion. Specific transporters and channels mediate vectorial movements of water and solutes in these segments. Although only a small percent of the glomerular filtrate reaches the CNT and CCD, these segments are critical for water and electrolyte homeostasis since several hormones, e.g. aldosterone and arginine vasopressin, exert their main effects in these nephron sites. Importantly, hormones regulate the function of the entire nephron and kidney by affecting channels and transporters in the CNT and CCD. Knowledge about the physiological and pathophysiological regulation of transport in the CNT and CCD and particular roles of specific channels/transporters has increased tremendously over the last two decades. Recent studies shed new light on several key questions concerning the regulation of renal transport. Precise distribution patterns of transport proteins in the CCD and CNT will be reviewed, and their physiological roles and mechanisms mediating ion transport in these segments will be also covered. Special emphasis will be given to pathophysiological conditions appearing as a result of abnormalities in renal transport in the CNT and CCD. PMID:23227301

  13. Design, implementation, and evaluation of an Internet of Things (IoT) network system for restaurant food waste management.

    Science.gov (United States)

    Wen, Zongguo; Hu, Shuhan; De Clercq, Djavan; Beck, M Bruce; Zhang, Hua; Zhang, Huanan; Fei, Fan; Liu, Jianguo

    2018-03-01

    Catering companies around the world generate tremendous amounts of waste; those in China are no exception. The paper discusses the design, implementation, and evaluation of a sensor-based Internet of Things (IoT) network technology for improving the management of restaurant food waste (RFW) in the city of Suzhou, China. This IoT-based system encompasses the generation, collection, transportation and final disposal of RFW. The Suzhou case study comprised four steps: (1) examination of the required functionality of an IoT-enabled system in the specific context of Suzhou; (2) configuration of the system architecture, both software and hardware components, according to the identified functionality; (3) installation of the components of the IoT system at the facilities of the stakeholders across the RFW generation-collection-transportation-disposal value chain; and (4) evaluation of the performance of the entire system, based on data from three years of operation. The results show that the system had a strong impact. Positive results include: (1) better management of RFW generation, as evidenced by a 20.5% increase in RFW collected via official channels and a 207% increase in the number of RFW generators under official contract; (2) better law enforcement in response to RFW malpractice, enabled by the monitoring capabilities of the IoT system; and (3) an overall reduction in illicit RFW activities and better process optimization across the RFW value chain. Negative results include: (1) Radio-frequency identification (RFID) tags need to be renewed often due to the frequent handling of waste bins, thus increasing operating costs; (2) dynamic/automatic weight sensors had a higher degree of error than the more time-consuming static/manual weighing method; and (3) there were disagreements between the city's government agencies about how to interpret data from the IoT system, which led to some inefficiencies in management. In sum, the Suzhou IoT system enabled data

  14. Modeling IoT-Based Solutions Using Human-Centric Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Álvaro Monares

    2014-08-01

    Full Text Available The Internet of Things (IoT has inspired solutions that are already available for addressing problems in various application scenarios, such as healthcare, security, emergency support and tourism. However, there is no clear approach to modeling these systems and envisioning their capabilities at the design time. Therefore, the process of designing these systems is ad hoc and its real impact is evaluated once the solution is already implemented, which is risky and expensive. This paper proposes a modeling approach that uses human-centric wireless sensor networks to specify and evaluate models of IoT-based systems at the time of design, avoiding the need to spend time and effort on early implementations of immature designs. It allows designers to focus on the system design, leaving the implementation decisions for a next phase. The article illustrates the usefulness of this proposal through a running example, showing the design of an IoT-based solution to support the first responses during medium-sized or large urban incidents. The case study used in the proposal evaluation is based on a real train crash. The proposed modeling approach can be used to design IoT-based systems for other application scenarios, e.g., to support security operatives or monitor chronic patients in their homes.

  15. Modeling IoT-based solutions using human-centric wireless sensor networks.

    Science.gov (United States)

    Monares, Álvaro; Ochoa, Sergio F; Santos, Rodrigo; Orozco, Javier; Meseguer, Roc

    2014-08-25

    The Internet of Things (IoT) has inspired solutions that are already available for addressing problems in various application scenarios, such as healthcare, security, emergency support and tourism. However, there is no clear approach to modeling these systems and envisioning their capabilities at the design time. Therefore, the process of designing these systems is ad hoc and its real impact is evaluated once the solution is already implemented, which is risky and expensive. This paper proposes a modeling approach that uses human-centric wireless sensor networks to specify and evaluate models of IoT-based systems at the time of design, avoiding the need to spend time and effort on early implementations of immature designs. It allows designers to focus on the system design, leaving the implementation decisions for a next phase. The article illustrates the usefulness of this proposal through a running example, showing the design of an IoT-based solution to support the first responses during medium-sized or large urban incidents. The case study used in the proposal evaluation is based on a real train crash. The proposed modeling approach can be used to design IoT-based systems for other application scenarios, e.g., to support security operatives or monitor chronic patients in their homes.

  16. Changes in T-cell subpopulations and cytokine network during early period of ibrutinib therapy in chronic lymphocytic leukemia patients: the significant decrease in T regulatory cells number.

    Science.gov (United States)

    Podhorecka, Monika; Goracy, Aneta; Szymczyk, Agnieszka; Kowal, Malgorzata; Ibanez, Blanca; Jankowska-Lecka, Olga; Macheta, Arkadiusz; Nowaczynska, Aleksandra; Drab-Urbanek, Elzbieta; Chocholska, Sylwia; Jawniak, Dariusz; Hus, Marek

    2017-05-23

    B cell receptor (BCR) stimulation signal plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), and kinase inhibitors directed toward the BCR pathway are now the promising anti-leukemic drugs. Ibrutinib, a Bruton tyrosine kinase inhibitor, demonstrates promising clinical activity in CLL. It is reported that ibrutinib, additionally to directly targeting leukemic cells, also inhibits the interactions of these cells with T cells, macrophages and accessory cells. Assessment of these mechanisms is important because of their non -direct anti-leukemic effects and to identify possible side effects connected with long-term drug administration.The aim of this study was to assess the in vivo effects of ibrutinib on T-cell subpopulations and cytokine network in CLL. The analysis was performed on a group of 19 patients during first month of ibrutinib therapy. The standard multicolor flow cytometry and cytometric bead array methods were used for assessment of T-cell subsets and cytokines/chemokines, respectively.The data obtained indicates that Ibrutinib treatment results in changes in T-cell subpopulations and cytokine network in CLL patients. Particularly, a significant reduction of T regulatory cells in peripheral blood was observed. By targeting these populations of T cells Ibrutinib can stimulate rejection of tumor cells by the immune system.

  17. Increased membrane cholesterol in lymphocytes diverts T-cells toward an inflammatory response.

    Directory of Open Access Journals (Sweden)

    Jacqueline Surls

    Full Text Available Cell signaling for T-cell growth, differentiation, and apoptosis is initiated in the cholesterol-rich microdomains of the plasma membrane known as lipid rafts. Herein, we investigated whether enrichment of membrane cholesterol in lipid rafts affects antigen-specific CD4 T-helper cell functions. Enrichment of membrane cholesterol by 40-50% following squalene administration in mice was paralleled by an increased number of resting CD4 T helper cells in periphery. We also observed sensitization of the Th1 differentiation machinery through co-localization of IL-2Rα, IL-4Rα, and IL-12Rβ2 subunits with GM1 positive lipid rafts, and increased STAT-4 and STAT-5 phosphorylation following membrane cholesterol enrichment. Antigen stimulation or CD3/CD28 polyclonal stimulation of membrane cholesterol-enriched, resting CD4 T-cells followed a path of Th1 differentiation, which was more vigorous in the presence of increased IL-12 secretion by APCs enriched in membrane cholesterol. Enrichment of membrane cholesterol in antigen-specific, autoimmune Th1 cells fostered their organ-specific reactivity, as confirmed in an autoimmune mouse model for diabetes. However, membrane cholesterol enrichment in CD4(+Foxp3(+ T-reg cells did not alter their suppressogenic function. These findings revealed a differential regulatory effect of membrane cholesterol on the function of CD4 T-cell subsets. This first suggests that membrane cholesterol could be a new therapeutic target to modulate the immune functions, and second that increased membrane cholesterol in various physiopathological conditions may bias the immune system toward an inflammatory Th1 type response.

  18. The hematopoietic chemokine CXCL12 promotes integration of human endothelial colony forming cell-derived cells into immature vessel networks.

    Science.gov (United States)

    Newey, Sarah E; Tsaknakis, Grigorios; Khoo, Cheen P; Athanassopoulos, Thanassi; Camicia, Rosalba; Zhang, Youyi; Grabowska, Rita; Harris, Adrian L; Roubelakis, Maria G; Watt, Suzanne M

    2014-11-15

    Proangiogenic factors, vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 (FGF-2) prime endothelial cells to respond to "hematopoietic" chemokines and cytokines by inducing/upregulating expression of the respective chemokine/cytokine receptors. Coculture of human endothelial colony forming cell (ECFC)-derived cells with human stromal cells in the presence of VEGF and FGF-2 for 14 days resulted in upregulation of the "hematopoietic" chemokine CXCL12 and its CXCR4 receptor by day 3 of coculture. Chronic exposure to the CXCR4 antagonist AMD3100 in this vasculo/angiogenesis assay significantly reduced vascular tubule formation, an observation recapitulated by delayed AMD3100 addition. While AMD3100 did not affect ECFC-derived cell proliferation, it did demonstrate a dual action. First, over the later stages of the 14-day cocultures, AMD3100 delayed tubule organization into maturing vessel networks, resulting in enhanced endothelial cell retraction and loss of complexity as defined by live cell imaging. Second, at earlier stages of cocultures, we observed that AMD3100 significantly inhibited the integration of exogenous ECFC-derived cells into established, but immature, vascular networks. Comparative proteome profiler array analyses of ECFC-derived cells treated with AMD3100 identified changes in expression of potential candidate molecules involved in adhesion and/or migration. Blocking antibodies to CD31, but not CD146 or CD166, reduced the ECFC-derived cell integration into these extant vascular networks. Thus, CXCL12 plays a key role not only in endothelial cell sensing and guidance, but also in promoting the integration of ECFC-derived cells into developing vascular networks.

  19. An immune-modulating diet increases the regulatory T cells and reduces T helper 1 inflammatory response in Leishmaniosis affected dogs treated with standard therapy.

    Science.gov (United States)

    Cortese, Laura; Annunziatella, Mariangela; Palatucci, Anna Teresa; Lanzilli, Sarah; Rubino, Valentina; Di Cerbo, Alessandro; Centenaro, Sara; Guidetti, Gianandrea; Canello, Sergio; Terrazzano, Giuseppe

    2015-12-03

    Clinical appearance and evolution of Canine Leishmaniosis (CL) are the consequence of complex interactions between the parasite and the genetic and immunological backgrounds. We investigated the effect of an immune-modulating diet in CL. Dogs were treated with anti- Leishmania pharmacological therapy combined with standard diet (SD Group) or with the immune-modulating diet (IMMD Group). CD3+ CD4+ Foxp3+ Regulatory T cells (Treg) and CD3+ CD4+ IFN-γ + T helper 1 (Th1) were analyzed by flow cytometry. All sick dogs showed low platelet number at diagnosis (T0). A platelet increase was observed after six months (T6) SD Group, with still remaining in the normal range at twelve months (T12). IMMD Group showed an increase in platelet number becoming similar to healthy dogs at T6 and T12. An increase of CD4/CD8 ratio was revealed in SD Group after three months (T3), while at T6 and at T12 the values resembled to T0. The increase in CD4/CD8 ratio at T3 was maintained at T6 and T12 in IMMD Group. A reduction in the percentage of Treg of all sick dogs was observed at T0. A recovery of Treg percentage was observed only at T3 in SD Group, while this effect disappeared at T6 and T12. In contrast, Treg percentage became similar to healthy animals in IMDD Group at T3, T6 and T12. Sick dogs showed an increase of Th1 cells at T0 as compared with healthy dogs. We observed the occurrence of a decrease of Th1 cells from T3 to T12 in SD Group, although a trend of increase was observed at T6 and T12. At variance, IMMD Group dogs showed a progressive decrease of Th1 cells, whose levels became similar to healthy controls at T6 and T12. The immune-modulating diet appears to regulate the immune response in CL during the standard pharmacological treatment. The presence of nutraceuticals in the diet correlates with the decrease of Th1 cells and with the increase of Treg in sick dogs. Therefore, the administration of the specific dietary supplement improved the clinical response to the

  20. Utilização de células-tronco autólogas de medula óssea na regeneração do nervo tibial de coelhos mediante técnica de tubulização com prótese de silicone Applyng of autologous stem cells from bone marrow in the regeneration of tibial nerve of rabbits using the tubulization technique with silicone tube

    Directory of Open Access Journals (Sweden)

    Lucas Marques Colomé

    2008-12-01

    Full Text Available Neste estudo é apresentado um modelo experimental de defeito agudo em nervo periférico para avaliação da regeneração nervosa mediante técnica de tubulização associada à inoculação de células-tronco autólogas de medula óssea. Foram utilizados 12 coelhos Nova Zelândia albinos, submetidos à secção bilateral e ao afastamento de 5mm do nervo tibial e posterior reparo mediante utilização de câmara de silicone. Internamente à prótese de tubulização do nervo tibial esquerdo em todos os animais, foram inoculadas células-tronco autólogas de medula óssea, coletadas a partir do úmero. Como grupo controle (nervo tibial direito, mediante aplicação da mesma técnica de reparo, solução de NaCl 0,9% foi administrada internamente à prótese. Após 30 dias de observação, os animais foram eutanasiados e foi realizada a avaliação histológica dos segmentos nervosos por meio das colorações de hematoxilina-eosina, luxol fast blue e azul de toluidina. Com os resultados, foi possível concluir que o transplante de células-tronco autólogas associado à técnica de tubulização apresenta vantagens no processo de regeneração nervosa periférica.This study presents an experimental model of an acute deffect in a peripheral nerve to evaluate neural regeneration using a tubulization technique associated with the inoculation of autologous stem cells from bone marrow. A total of 12 New Zealand white rabbits underwent a bilateral dissection of the tibial nerve followed by repair with silicone tubulization. On the left tibial nerve of all animals, the tube was filled with autologous bone marrow-derived stem cells collected from the humerus. For control, using the same repair technique, the tubes were filled with a NaCl solution in the right tibial nerve. After 30 days of observation, the animals were euthanized and a histological evaluation of the collected nerve segments was performed by staining with hematoxylin-eosin, luxol fast

  1. Network Capacity Assessment and Increase in Systems with Intermittent Water Supply

    OpenAIRE

    Ilaya-Ayza, Amilkar Ernesto; Campbell-Gonzalez, Enrique; Pérez García, Rafael; Izquierdo Sebastián, Joaquín

    2016-01-01

    [EN] Water supply systems have been facing many challenges in recent decades due to the potential effects of climate change and rapid population growth. Water systems need to expand because of demographic growth. Therefore, evaluating and increasing system capacity is crucial. Specifically, we analyze network capacity as one of the main features of a system. When the network capacity starts to decrease, there is a risk that continuous supply will become intermittent. This paper discusses how...

  2. Software defined networking for improved wireless sensor network management: a survey

    CSIR Research Space (South Africa)

    Ndiaye, M

    2017-05-01

    Full Text Available Wireless sensor networks (WSNs) are becoming increasingly popular with the advent of the Internet of things (IoT). Various real-world applications of WSNs such as in smart grids, smart farming and smart health would require a potential deployment...

  3. Exploiting IoT Technologies and Open Source Components for Smart Seismic Network Instrumentation

    Science.gov (United States)

    Germenis, N. G.; Koulamas, C. A.; Foundas, P. N.

    2017-12-01

    The data collection infrastructure of any seismic network poses a number of requirements and trade-offs related to accuracy, reliability, power autonomy and installation & operational costs. Having the right hardware design at the edge of this infrastructure, embedded software running inside the instruments is the heart of pre-processing and communication services implementation and their integration with the central storage and processing facilities of the seismic network. This work demonstrates the feasibility and benefits of exploiting software components from heterogeneous sources in order to realize a smart seismic data logger, achieving higher reliability, faster integration and less development and testing costs of critical functionality that is in turn responsible for the cost and power efficient operation of the device. The instrument's software builds on top of widely used open source components around the Linux kernel with real-time extensions, the core Debian Linux distribution, the earthworm and seiscomp tooling frameworks, as well as components from the Internet of Things (IoT) world, such as the CoAP and MQTT protocols for the signaling planes, besides the widely used de-facto standards of the application domain at the data plane, such as the SeedLink protocol. By using an innovative integration of features based on lower level GPL components of the seiscomp suite with higher level processing earthworm components, coupled with IoT protocol extensions to the latter, the instrument can implement smart functionality such as network controlled, event triggered data transmission in parallel with edge archiving and on demand, short term historical data retrieval.

  4. Whitelists Based Multiple Filtering Techniques in SCADA Sensor Networks

    Directory of Open Access Journals (Sweden)

    DongHo Kang

    2014-01-01

    Full Text Available Internet of Things (IoT consists of several tiny devices connected together to form a collaborative computing environment. Recently IoT technologies begin to merge with supervisory control and data acquisition (SCADA sensor networks to more efficiently gather and analyze real-time data from sensors in industrial environments. But SCADA sensor networks are becoming more and more vulnerable to cyber-attacks due to increased connectivity. To safely adopt IoT technologies in the SCADA environments, it is important to improve the security of SCADA sensor networks. In this paper we propose a multiple filtering technique based on whitelists to detect illegitimate packets. Our proposed system detects the traffic of network and application protocol attacks with a set of whitelists collected from normal traffic.

  5. [3H]PN200-110 and [3H]ryanodine binding and reconstitution of ion channel activity with skeletal muscle membranes

    International Nuclear Information System (INIS)

    Hamilton, S.L.; Alvarez, R.M.; Fill, M.; Hawkes, M.J.; Brush, K.L.; Schilling, W.P.; Stefani, E.

    1989-01-01

    Skeletal muscle membranes derived either from the tubular (T) network or from the sarcoplasmic reticulum (SR) were characterized with respect to the binding of the dihydropyridine, [ 3 H]PN200-110, and the alkaloid, [ 3 H]ryanodine; polypeptide composition; and ion channel activity. Conditions for optimizing the binding of these radioligands are discussed. A bilayer pulsing technique is described and is used to examine the channels present in these membranes. Fusion of T-tubule membranes into bilayers revealed the presence of chloride channels and dihydropyridine-sensitive calcium channels with three distinct conductances. The dihydropyridine-sensitive channels were further characterized with respect to their voltage dependence. Pulsing experiments indicated that two different populations of dihydropyridine-sensitive channels existed. Fusion of heavy SR vesicles revealed three different ion channels; the putative calcium release channel, a potassium channel, and a chloride channel. Thus, this fractionation procedure provides T-tubules and SR membranes which, with radioligand binding and single channel recording techniques, provide a useful tool to study the characteristics of skeletal muscle ion channels and their possible role in excitation-contraction coupling

  6. SACA: Self-Aware Communication Architecture for IoT Using Mobile Fog Servers

    Directory of Open Access Journals (Sweden)

    Vishal Sharma

    2017-01-01

    Full Text Available Internet of things (IoT aims at bringing together large business enterprise solutions and architectures for handling the huge amount of data generated by millions of devices. For this aim, IoT is necessary to connect various devices and provide a common platform for storage and retrieval of information without fail. However, the success of IoT depends on the novelty of network and its capability in sustaining the increasing demand by users. In this paper, a self-aware communication architecture (SACA is proposed for sustainable networking over IoT devices. The proposed approach employs the concept of mobile fog servers which make relay using the train and unmanned aerial vehicle (UAV networks. The problem is presented based on Wald’s maximum model, which is resolved by the application of a distributed node management (DNM system and state dependency formulations. The proposed approach is capable of providing prolonged connectivity by increasing the network reliability and sustainability even in the case of failures. The effectiveness of the proposed approach is demonstrated through numerical and network simulations in terms of significant gains attained with lesser delay and fewer packet losses. The proposed approach is also evaluated against Sybil, wormhole, and DDoS attacks for analyzing its sustainability and probability of connectivity in unfavorable conditions.

  7. A shift toward T helper 2 responses and an increase in modulators of innate immunity in depressed patients treated with escitalopram.

    Science.gov (United States)

    Ho, Pei-Shen; Yeh, Yi-Wei; Huang, San-Yuan; Liang, Chih-Sung

    2015-03-01

    Depression is hypothesized to involve inflammatory processes, and identifying the key cytokines targeted by antidepressant drugs is critical for tailoring treatment to specific cases. However, investigating a limited number of cytokines at one time cannot provide a broad picture of antidepressant-associated immunomodulation. Cytokines act in a network where one could demonstrate pleiotropism, redundancy, synergy, and antagonism with other cytokine functions. This study was aimed at determining whether escitalopram functions as an anti-inflammatory agent and, if so, how it influences cytokine networks. A total of 24 healthy controls and 26 patients with clinical depression requiring inpatient treatment were recruited. A multiplex assay, an efficient tool to simultaneously measure 27 cytokines, was applied in patients with depression before and after 4-week escitalopram treatment. Healthy controls did not take escitalopram and completed cytokine analyses once. We demonstrated that escitalopram increased the levels of interleukin (IL)-1 receptor antagonist and IL-2. Moreover, escitalopram contributed to a shift toward T helper 2 responses and an increase in modulators of innate immunity, leading to a decrease of immune system activation, both innate and adaptive. We suggest that escitalopram modulates the balance of IL-1 and IL-1 receptor antagonist and improves the function and number of T regulatory cells. However, diverse conclusions could be drawn if only a few cytokines were assessed or different significance levels were used. Further studies should investigate a wide range of cytokines in a reliable and valid way, which is key to disentangling the effects of different antidepressants on inflammatory processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Acute hypotension induced by aortic clamp vs. PTH provokes distinct proximal tubule Na+ transporter redistribution patterns

    DEFF Research Database (Denmark)

    Leong, Patrick K K; Yang, Li E; Lin, Harrison W

    2004-01-01

    . This study aimed to determine the effects of acute hypotension, induced by aortic clamp or by high-dose PTH (100 microg PTH/kg), on renal hemodynamics and proximal tubule Na/H exchanger isoform 3 (NHE3) and type IIa Na-P(i) cotransporter protein (NaPi2) distribution. Subcellular distribution was analyzed...... clearance. There was, however, no significant change in glomerular filtration rate (GFR) or subcellular distribution of NHE3 and NaPi2. In contrast, high-dose PTH rapidly (

  9. Ibrutinib Therapy Increases T Cell Repertoire Diversity in Patients with Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Yin, Qingsong; Sivina, Mariela; Robins, Harlan; Yusko, Erik; Vignali, Marissa; O'Brien, Susan; Keating, Michael J; Ferrajoli, Alessandra; Estrov, Zeev; Jain, Nitin; Wierda, William G; Burger, Jan A

    2017-02-15

    The Bruton's tyrosine kinase inhibitor ibrutinib is a highly effective, new targeted therapy for chronic lymphocytic leukemia (CLL) that thwarts leukemia cell survival, growth, and tissue homing. The effects of ibrutinib treatment on the T cell compartment, which is clonally expanded and thought to support the growth of malignant B cells in CLL, are not fully characterized. Using next-generation sequencing technology, we characterized the diversity of TCRβ-chains in peripheral blood T cells from 15 CLL patients before and after 1 y of ibrutinib therapy. We noted elevated CD4 + and CD8 + T cell numbers and a restricted TCRβ repertoire in all pretreatment samples. After 1 y of ibrutinib therapy, elevated peripheral blood T cell numbers and T cell-related cytokine levels had normalized, and T cell repertoire diversity increased significantly. Dominant TCRβ clones in pretreatment samples declined or became undetectable, and the number of productive unique clones increased significantly during ibrutinib therapy, with the emergence of large numbers of low-frequency TCRβ clones. Importantly, broader TCR repertoire diversity was associated with clinical efficacy and lower rates of infections during ibrutinib therapy. These data demonstrate that ibrutinib therapy increases diversification of the T cell compartment in CLL patients, which contributes to cellular immune reconstitution. Copyright © 2017 by The American Association of Immunologists, Inc.

  10. Network for the increase of the industrial energy efficiency; Mreza industrijske energetske efikasnosti (MIEE)

    Energy Technology Data Exchange (ETDEWEB)

    Krstulovic, V [Energetski institut Hrvoje Pozar, Zagreb (Croatia)

    1997-12-31

    Introduction of the idea of a network for the increase of the industrial energy efficiency, international activities in that area, some experiences, targets and plan of the building of such network in Croatia. (author). 3 figs.

  11. Tariff regulation and profitability of energy networks. A model analysis for TenneT TSO

    International Nuclear Information System (INIS)

    Mulder, M.

    2010-12-01

    In this paper we analyse the impact of the regulatory framework for the new regulatory period (2011-2013) on the long-term profitability of TenneT TSO, the operator of the high-voltage electricity network in the Netherlands. Long-term profitability is a key component of the financeability of a firm. In the long run, the return on capital should be at least equal to the opportunity costs of capital in order to finance investments. As the ultimate indicator for the long-term profitability, we use the net present value of economic profit, which is the difference between total revenues and total costs, including a normal return on capital. In order to simulate the future financial development of the TSO, we developed a model. On the basis of the model analysis, making a number of methodological assumptions, we conclude that the tariff regulation results in a positive long-term profitability, implying that the regulatory framework enables TenneT TSO to finance its investments in replacement and network expansion. In the long run all costs, including the normal costs of capital, will be fully compensated by the revenues, resulting in a (slightly) positive net present value of economic profit. This conclusion is subject to the condition that the TSO eliminates the existing inefficiencies in the network and that it is able to annually improve its overall efficiency. If this condition is not met, the shareholder might face a loss of more than one hundred million Euros.

  12. HEPES activates a MiT/TFE-dependent lysosomal-autophagic gene network in cultured cells: A call for caution.

    Science.gov (United States)

    Tol, Marc J; van der Lienden, Martijn J C; Gabriel, Tanit L; Hagen, Jacob J; Scheij, Saskia; Veenendaal, Tineke; Klumperman, Judith; Donker-Koopman, Wilma E; Verhoeven, Arthur J; Overkleeft, Hermen; Aerts, Johannes M; Argmann, Carmen A; van Eijk, Marco

    2018-01-01

    In recent years, the lysosome has emerged as a highly dynamic, transcriptionally regulated organelle that is integral to nutrient-sensing and metabolic rewiring. This is coordinated by a lysosome-to-nucleus signaling nexus in which MTORC1 controls the subcellular distribution of the microphthalmia-transcription factor E (MiT/TFE) family of "master lysosomal regulators". Yet, despite the importance of the lysosome in cellular metabolism, the impact of traditional in vitro culture media on lysosomal dynamics and/or MiT/TFE localization has not been fully appreciated. Here, we identify HEPES, a chemical buffering agent that is broadly applied in cell culture, as a potent inducer of lysosome biogenesis. Supplementation of HEPES to cell growth media is sufficient to decouple the MiT/TFE family members-TFEB, TFE3 and MITF-from regulatory mechanisms that control their cytosolic retention. Increased MiT/TFE nuclear import in turn drives the expression of a global network of lysosomal-autophagic and innate host-immune response genes, altering lysosomal dynamics, proteolytic capacity, autophagic flux, and inflammatory signaling. In addition, siRNA-mediated MiT/TFE knockdown effectively blunted HEPES-induced lysosome biogenesis and gene expression profiles. Mechanistically, we show that MiT/TFE activation in response to HEPES requires its macropinocytic ingestion and aberrant lysosomal storage/pH, but is independent of MTORC1 signaling. Altogether, our data underscore the cautionary use of chemical buffering agents in cell culture media due to their potentially confounding effects on experimental results.

  13. Study on Increasing High Temperature pH(t) to Reduce Iron Corrosion Products

    International Nuclear Information System (INIS)

    Shin, Dong Man; Hur, Nam Yong; Kim, Waang Bae

    2011-01-01

    The transportation and deposition of iron corrosion products are important elements that affect both the steam generator (SG) integrity and secondary system in pressurized water reactor (PWR) nuclear power plants. Most of iron corrosion products are generated on carbon steel materials due to flow accelerated corrosion (FAC). The several parameters like water chemistry, temperature, hydrodynamic, and steel composition affect FAC. It is well established that the at-temperature pH of the deaerated water system has a first order effect on the FAC rate of carbon steels through nuclear industry researches. In order to reduce transportation and deposition of iron corrosion products, increasing pH(t) tests were applied on secondary system of A, B units. Increasing pH(t) successfully reduced flow accelerated corrosion. The effect of increasing pH(t) to inhibit FAC was identified through the experiment and pH(t) evaluation in this paper

  14. Osteocyte Lacunae are Lenticular/Ellipsoid Spaces or Spiral/Helical Tubules

    Directory of Open Access Journals (Sweden)

    Bijit Kanti Guha

    2017-10-01

    Full Text Available Introduction: According to the current concept of bone structure, the osteocyte lacunae are lenticular or ellipsoid spaces occupied by osteocytes. These osteocytes are thought to communicate with each other through a tubular system made up of Canaliculi. The rest of the structures i.e., Haversian canal, and Volkmann’s canal are also tubular in shape. Considering this existing concept of bone microstructure described by various authors, it is highly unlikely that the lacunae alone would be lenticular/ellipsoid structure. In the present study author wanted to know that amongst the all tubular spaces, what is the reason that only the osteocyte lacunae are lenticular or ellipsoid structure? Also to investigate whether these lenticular spaces are really lenticular/ellipsoid or they are cut sections of tubes, which are lying helically or spirally. It is well known from various previous studies that Haversian canal, Volkmann’s canal and Canaliculi are tubular shaped structures and how it is possible that lenticular/ellipsoid structure can present amongst them. So we thought that, it may be possible that these lenticular spaces are not actually lenticular but this lenticular shape is due to the cut sections of any type of tubule in various possible planes (i.e., transverse, longitudinal and various degrees of oblique plane. Aim: The present study was carried out to reinvestigate the shape of the osteocyte lacunae amongst the tubular system (i.e., Haversian canal, Volkmann’s canal and Canaliculi of compact bone. Materials and Methods: The study is carried out by preparing thin sections of adult bones (ground glass preparation and visualizing them under binocular light microscope and scanelectron microscope after following proper procedure. Results: We observed that the lacunae are actually spirally/helically placed tubules with several branching. These branching are considered as canaliculi. These branching are of various diameters and they

  15. Increased Incidence of T-Cell Malignancies in Patients with Chronic Lymphocytic Leukemia

    OpenAIRE

    Choi, Goda; van den Broek, Esther C; Stam, Olga CG; van Noesel, C.J.M.; Tonino, Sanne H.; Kater, Armon P.

    2015-01-01

    We present a patient with chemotherapy-refractory Chronic Lymphocytic Leukemia (CLL) in whom postmortem examination showed hepatosplenomegaly, with both multiple small-cellular CLL lesions and large-cellular, monoclonal T-cell infiltrates. Following this case, the co-incidence of T-cell malignancies and CLL was studied using Dutch and American cancer registry databases. Analysis showed an excess risk for T-cell malignancies in CLL patients, with increased standardized incidence ratios compare...

  16. Functional connectivity substrates for tDCS response in Minimally Conscious State patients

    Directory of Open Access Journals (Sweden)

    Carlo Cavaliere

    2016-11-01

    Full Text Available Transcranial direct current stimulation (tDCS is a non-invasive technique recently employed in disorders of consciousness, and determining a transitory recovery of signs of consciousness in almost half of minimally conscious state (MCS patients. Although the rising evidences about its possible role in the treatment of many neurological and psychiatric conditions, no evidences exist about brain functional connectivity substrates underlying tDCS response. We retrospectively evaluated resting state functional Magnetic Resonance Imaging (fMRI of 16 sub-acute and chronic MCS patients (6 tDCS responders who successively received a single left dorsolateral prefrontal cortex (DLPFC tDCS in a double-blind randomized cross-over trial. A seed-based approach for regions of left extrinsic control network and default-mode network was performed.TDCS responders showed an increased left intra-network connectivity for regions co-activated with left DLPFC, and significantly with left inferior frontal gyrus. Non-responders MCS patients showed an increased connectivity between left DLPFC and midline cortical structures, including anterior cingulate cortex and precuneus.Our findings suggest that a prior high connectivity with regions belonging to extrinsic control network can facilitate transitory recovery of consciousness in a subgroup of MCS patients that underwent tDCS treatment. Therefore, resting state-fMRI could be very valuable in detecting the neuronal conditions necessary for tDCS to improve behavior in MCS.

  17. Effects of induced Na+/Ca2+ exchanger overexpression on the spatial distribution of L-type Ca2+ channels and junctophilin-2 in pressure-overloaded hearts.

    Science.gov (United States)

    Ujihara, Yoshihiro; Mohri, Satoshi; Katanosaka, Yuki

    2016-11-25

    The Na + /Ca 2+ exchanger 1 (NCX1) is an essential Ca 2+ efflux system in cardiomyocytes. Although NCX1 is distributed throughout the sarcolemma, a subpopulation of NCX1 is localized to transverse (T)-tubules. There is growing evidence that T-tubule disorganization is a causal event that shifts the transition from hypertrophy to heart failure (HF). However, the detailed molecular mechanisms have not been clarified. Previously, we showed that induced NCX1 expression in pressure-overloaded hearts attenuates defective excitation-contraction coupling and HF progression. Here, we examined the effects of induced NCX1 overexpression on the spatial distribution of L-type Ca 2+ channels (LTCCs) and junctophilin-2 (JP2), a structural protein that connects the T-tubule and sarcoplasmic reticulum membrane, in pressure-overloaded hearts. Quantitative analysis showed that the regularity of NCX1 localization was significantly decreased at 8 weeks after transverse aortic constriction (TAC)-surgery; however, T-tubule organization and the regularities of LTCC and JP2 immunofluorescent signals were maintained at this time point. These observations demonstrated that release of NCX1 from the T-tubule area occurred before the onset of T-tubule disorganization and LTCC and JP2 mislocalization. Moreover, induced NCX1 overexpression at 8 weeks post-TAC not only recovered NCX1 regularity but also prevented the decrease in LTCC and JP2 regularities at 16 weeks post-TAC. These results suggested that NCX1 may play an important role in the proper spatial distribution of LTCC and JP2 in T-tubules in the context of pressure-overloading. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Dragon enhances BMP signaling and increases transepithelial resistance in kidney epithelial cells.

    Science.gov (United States)

    Xia, Yin; Babitt, Jodie L; Bouley, Richard; Zhang, Ying; Da Silva, Nicolas; Chen, Shanzhuo; Zhuang, Zhenjie; Samad, Tarek A; Brenner, Gary J; Anderson, Jennifer L; Hong, Charles C; Schneyer, Alan L; Brown, Dennis; Lin, Herbert Y

    2010-04-01

    The neuronal adhesion protein Dragon acts as a bone morphogenetic protein (BMP) coreceptor that enhances BMP signaling. Given the importance of BMP signaling in nephrogenesis and its putative role in the response to injury in the adult kidney, we studied the localization and function of Dragon in the kidney. We observed that Dragon localized predominantly to the apical surfaces of tubular epithelial cells in the thick ascending limbs, distal convoluted tubules, and collecting ducts of mice. Dragon expression was weak in the proximal tubules and glomeruli. In mouse inner medullary collecting duct (mIMCD3) cells, Dragon generated BMP signals in a ligand-dependent manner, and BMP4 is the predominant endogenous ligand for the Dragon coreceptor. In mIMCD3 cells, BMP4 normally signaled through BMPRII, but Dragon enhanced its signaling through the BMP type II receptor ActRIIA. Dragon and BMP4 increased transepithelial resistance (TER) through the Smad1/5/8 pathway. In epithelial cells isolated from the proximal tubule and intercalated cells of collecting ducts, we observed coexpression of ActRIIA, Dragon, and BMP4 but not BMPRII. Taken together, these results suggest that Dragon may enhance BMP signaling in renal tubular epithelial cells and maintain normal renal physiology.

  19. Numerical variation of cell lysosomes of the proximal convoluted tubules of mice Kidneys submitted to different X-ray doses

    International Nuclear Information System (INIS)

    Silva Lapa, R. de C.R. da; Pacheco, I.P.; Segreto, C.

    1984-01-01

    The number of cell lysosomes of the proximal convoluted tubules of mice Kidneys (Mus musculus) before and after whole-body irradiation with different X-ray doses is confronted. The mice were sacrificed after 72 hours and the cortex fragments were conduct to electron microscopy. A statistically significant numerical reduction of the lysosomas was observed in 72 hours. (M.A.C.) [pt

  20. Design of an IoT Enabled Local Network Based Home Monitoring System with a Priority Scheme

    Directory of Open Access Journals (Sweden)

    V. Tiwari

    2017-04-01

    Full Text Available Internet of things (IoT is a concept where all devices get connected to the internet to exchange information. IoT can be utilized in order to make a home environment interactive and smart. The required connectivity can be provided by either making all the devices Wi-Fi capable, which is costly, or by setting a local wireless sensor network (WSN which later connects to internet. In this work various devices and sensors are designed and connected in a wireless sensor network within a home environment which generates a sensor dependent data packet. These data packets are then sent to the cloud through a master node. The master sends the data using a proposed priority scheme so that the critical information can be sent early. Simulations were performed to show that under the proposed scheme the loss of critical sensors information is reduced by around 75%.

  1. RNA-Seq Comparison of Larval and Adult Malpighian Tubules of the Yellow Fever Mosquito Aedes aegypti Reveals Life Stage-Specific Changes in Renal Function

    Directory of Open Access Journals (Sweden)

    Yiyi Li

    2017-05-01

    Full Text Available Introduction: The life history of Aedes aegypti presents diverse challenges to its diuretic system. During the larval and pupal life stages mosquitoes are aquatic. With the emergence of the adult they become terrestrial. This shifts the organism within minutes from an aquatic environment to a terrestrial environment where dehydration has to be avoided. In addition, female mosquitoes take large blood meals, which present an entirely new set of challenges to salt and water homeostasis.Methods: To determine differences in gene expression associated with these different life stages, we performed an RNA-seq analysis of the main diuretic tissue in A. aegypti, the Malpighian tubules. We compared transcript abundance in 4th instar larvae to that of adult females and analyzed the data with a focus on transcripts that encode proteins potentially involved in diuresis, like water and solute channels as well as ion transporters. We compared our results against the model of potassium- and sodium chloride excretion in the Malpighian tubules proposed by Hine et al. (2014, which involves at least eight ion transporters and a proton-pump.Results: We found 3,421 of a total number of 17,478 (19.6% unique transcripts with a P < 0.05 and at least a 2.5 fold change in expression levels between the two groups. We identified two novel transporter genes that are highly expressed in the adult Malpighian tubules, which have not previously been part of the transport model in this species and may play important roles in diuresis. We also identified candidates for hypothesized sodium and chloride channels. Detoxification genes were generally higher expressed in larvae.Significance: This study represents the first comparison of Malpighian tubule transcriptomes between larval and adult A. aegypti mosquitoes, highlighting key differences in their renal systems that arise as they transform from an aquatic filter-feeding larval stage to a terrestrial, blood-feeding adult stage.

  2. Increasing extracellular matrix collagen level and MMP activity induces cyst development in polycystic kidney disease.

    Science.gov (United States)

    Liu, Bin; Li, Chenghai; Liu, Zijuan; Dai, Zonghan; Tao, Yunxia

    2012-09-11

    Polycystic Kidney Disease (PKD) kidneys exhibit increased extracellular matrix (ECM) collagen expression and metalloproteinases (MMPs) activity. We investigated the role of these increases on cystic disease progression in PKD kidneys. We examined the role of type I collagen (collagen I) and membrane bound type 1 MMP (MT1-MMP) on cyst development using both in vitro 3 dimensional (3D) collagen gel culture and in vivo PCK rat model of PKD. We found that collagen concentration is critical in controlling the morphogenesis of MDCK cells cultured in 3D gels. MDCK cells did not form 3D structures at collagen I concentrations lower than 1 mg/ml but began forming tubules when the concentration reaches 1 mg/ml. Significantly, these cells began to form cyst when collagen I concentration reached to 1.2 mg/ml, and the ratios of cyst to tubule structures increased as the collagen I concentration increased. These cells exclusively formed cyst structures at a collagen I concentration of 1.8 mg/ml or higher. Overexpression of MT1-MMP in MDCK cells significantly induced cyst growth in 3D collagen gel culture. Conversely, inhibition of MMPs activity with doxycycline, a FDA approved pan-MMPs inhibitor, dramatically slowed cyst growth. More importantly, the treatment of PCK rats with doxycycline significantly decreased renal tubule cell proliferation and markedly inhibited the cystic disease progression. Our data suggest that increased collagen expression and MMP activity in PKD kidneys may induce cyst formation and expansion. Our findings also suggest that MMPs may serve as a therapeutic target for the treatment of human PKD.

  3. Increasing extracellular matrix collagen level and MMP activity induces cyst development in polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Liu Bin

    2012-09-01

    Full Text Available Abstract Background Polycystic Kidney Disease (PKD kidneys exhibit increased extracellular matrix (ECM collagen expression and metalloproteinases (MMPs activity. We investigated the role of these increases on cystic disease progression in PKD kidneys. Methods We examined the role of type I collagen (collagen I and membrane bound type 1 MMP (MT1-MMP on cyst development using both in vitro 3 dimensional (3D collagen gel culture and in vivo PCK rat model of PKD. Results We found that collagen concentration is critical in controlling the morphogenesis of MDCK cells cultured in 3D gels. MDCK cells did not form 3D structures at collagen I concentrations lower than 1 mg/ml but began forming tubules when the concentration reaches 1 mg/ml. Significantly, these cells began to form cyst when collagen I concentration reached to 1.2 mg/ml, and the ratios of cyst to tubule structures increased as the collagen I concentration increased. These cells exclusively formed cyst structures at a collagen I concentration of 1.8 mg/ml or higher. Overexpression of MT1-MMP in MDCK cells significantly induced cyst growth in 3D collagen gel culture. Conversely, inhibition of MMPs activity with doxycycline, a FDA approved pan-MMPs inhibitor, dramatically slowed cyst growth. More importantly, the treatment of PCK rats with doxycycline significantly decreased renal tubule cell proliferation and markedly inhibited the cystic disease progression. Conclusions Our data suggest that increased collagen expression and MMP activity in PKD kidneys may induce cyst formation and expansion. Our findings also suggest that MMPs may serve as a therapeutic target for the treatment of human PKD.

  4. Artificial Neural Network based control for PV/T panel to track optimum thermal and electrical power

    International Nuclear Information System (INIS)

    Ben Ammar, Majed; Chaabene, Maher; Chtourou, Zied

    2013-01-01

    Highlights: ► We establish a state model of PV/T panel. ► We study the effect of mass flow rate on PV/T efficiency. ► A real time PV/T control algorithm is proposed. ► A model based optimal thermal and electrical power operation point is tracked. - Abstract: As solar energy is intermittent, many algorithms and electronics have been developed to track the maximum power generation from photovoltaic and thermal panels. Following technological advances, these panels are gathered into one unit: PV/T system. PV/T delivers simultaneously two kinds of power: electrical power and thermal power. Nevertheless, no control systems have been developed in order to track maximum power generation from PV/T system. This paper suggests a PV/T control algorithm based on Artificial Neural Network (ANN) to detect the optimal power operating point (OPOP) by considering PV/T model behavior. The OPOP computes the optimum mass flow rate of PV/T for a considered irradiation and ambient temperature. Simulation results demonstrate great concordance between OPOP model based calculation and ANN outputs.

  5. Influence of extracellular HCO3- and pH on lysine (LYS) and leucine (LEU) uptake and metabolism in swine renal tubules

    International Nuclear Information System (INIS)

    Patience, J.F.; Esteve-Garcia, E.; Austic, R.E.

    1986-01-01

    Fragments of renal tubules prepared by collagenase treatment of renal cortex were suspended to Krebs-Henseleit buffers which were modified to contain 10, 25 and 35 mM HCO 3 - at pH 7.4, or 25 mM HCO 3 - at pH 7.1, 7.4 and 7.7. Buffers were oxygenated with O 2 -CO 2 gas mixtures varying in carbon dioxide concentration prior to incubation. Approximately 100 mg tubules were incubated with shaking at 37 0 C for 30 min in serum-stoppered 25 ml Erlenmeyer flasks in 3.0 ml of buffer containing 0.1% dialyzed bovine serum albumin, 5 mM D-glucose and 0.3 mM L-[U- 14 C]-lysine or L-[1- 14 C]-leucine. The incorporation of carbon-14 into CO 2 and into 10% sulfosalicylic acid (SSA)-soluble and SSA-insoluble fractions of the incubation mixture was determined. Low (10mM) bicarbonate reduced the incorporation of lys and leu into protein but did not substantially affect the recovery of 14 CO 2 from either amino acid. High pH (7.7) resulted in reduced incorporation of lys and leu into protein, and decreased the oxidation of lys but not leu. The specific activity of lys (leu was not determined) in the SSA-soluble fraction was unaffected by bicarbonate or pH. The authors conclude that variations in extracellular pH and HCO 3 - (or pCO 2 ) affect the metabolism of amino acids by renal tubules and that low extracellular HCO 3 - (or pCO 2 ) may depress the incorporation of amino acids into protein

  6. Discrimination of panti p → tanti t events by a neural network classifier

    International Nuclear Information System (INIS)

    Cherubini, A.; Odorico, R.

    1992-01-01

    Neural network and conventional statistical techniques are compared in the problem of discriminating panti p→tanti t events, with top quarks decaying into anything, from the associated hadronic background at the energy of the Fermilab collider. The NN we develop for this sake is an improved version of Kohonen's learning vector quantization scheme. Performance of the NN as a tanti t event classifier is found to be less satisfactory than that achievable by statistical methods. We conclude that the probable reasons for that are: i) The NN approach presents advantages only when dealing with event distributions in the feature space which substantially differ from Gaussians; ii) NN's require much larger training sets of events than statistical discrimination in order to give comparable results. (orig.)

  7. Increasing network lifetime by battery-aware master selection in radio networks

    NARCIS (Netherlands)

    de Graaf, Maurits; van Ommeren, Jan C.W.; Brogle, Marc; Heijenk, Gerhard J.; Braun, Torsten; Konstantas, D.

    2009-01-01

    Mobile wireless communication systems often need to maximize their network lifetime (defined as the time until the first node runs out of energy). In the broadcast network lifetime problem, all nodes are sending broadcast traffic, and one asks for an assignment of transmit powers to nodes, and for

  8. Cooperation of the ER-shaping proteins atlastin, lunapark, and reticulons to generate a tubular membrane network

    OpenAIRE

    Wang, Songyu; Tukachinsky, Hanna; Romano, Fabian B; Rapoport, Tom A

    2016-01-01

    eLife digest The endoplasmic reticulum is a compartment within the cells of plants, animals and other eukaryotes. This compartment plays a number of roles within cells, for example, serving as the site where many proteins and fat molecules are built. Most often the endoplasmic reticulum exists as a network of thin tubules. However, this shape changes during the lifetime of a single cell, and the endoplasmic reticulum converts into flattened structures known as sheets when the cell divides. Th...

  9. Increased frontal functional networks in adult survivors of childhood brain tumors

    Directory of Open Access Journals (Sweden)

    Hongbo Chen

    2016-01-01

    Full Text Available Childhood brain tumors and associated treatment have been shown to affect brain development and cognitive outcomes. Understanding the functional connectivity of brain many years after diagnosis and treatment may inform the development of interventions to improve the long-term outcomes of adult survivors of childhood brain tumors. This work investigated the frontal region functional connectivity of 16 adult survivors of childhood cerebellar tumors after an average of 14.9 years from diagnosis and 16 demographically-matched controls using resting state functional MRI (rs-fMRI. Independent component analysis (ICA was applied to identify the resting state activity from rs-fMRI data and to select the specific regions associated with executive functions, followed by the secondary analysis of the functional networks connecting these regions. It was found that survivors exhibited differences in the functional connectivity in executive control network (ECN, default mode network (DMN and salience network (SN compared to demographically-matched controls. More specifically, the number of functional connectivity observed in the survivors is higher than that in the controls, and with increased strength, or stronger correlation coefficient between paired seeds, in survivors compared to the controls. Observed hyperconnectivity in the selected frontal functional network thus is consistent with findings in patients with other neurological injuries and diseases.

  10. Altered Integration of Structural Covariance Networks in Young Children With Type 1 Diabetes.

    Science.gov (United States)

    Hosseini, S M Hadi; Mazaika, Paul; Mauras, Nelly; Buckingham, Bruce; Weinzimer, Stuart A; Tsalikian, Eva; White, Neil H; Reiss, Allan L

    2016-11-01

    Type 1 diabetes mellitus (T1D), one of the most frequent chronic diseases in children, is associated with glucose dysregulation that contributes to an increased risk for neurocognitive deficits. While there is a bulk of evidence regarding neurocognitive deficits in adults with T1D, little is known about how early-onset T1D affects neural networks in young children. Recent data demonstrated widespread alterations in regional gray matter and white matter associated with T1D in young children. These widespread neuroanatomical changes might impact the organization of large-scale brain networks. In the present study, we applied graph-theoretical analysis to test whether the organization of structural covariance networks in the brain for a cohort of young children with T1D (N = 141) is altered compared to healthy controls (HC; N = 69). While the networks in both groups followed a small world organization-an architecture that is simultaneously highly segregated and integrated-the T1D network showed significantly longer path length compared with HC, suggesting reduced global integration of brain networks in young children with T1D. In addition, network robustness analysis revealed that the T1D network model showed more vulnerability to neural insult compared with HC. These results suggest that early-onset T1D negatively impacts the global organization of structural covariance networks and influences the trajectory of brain development in childhood. This is the first study to examine structural covariance networks in young children with T1D. Improving glycemic control for young children with T1D might help prevent alterations in brain networks in this population. Hum Brain Mapp 37:4034-4046, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Induction of apoptosis in cultured human proximal tubule cells by fumonisins and fumonisin metabolites

    International Nuclear Information System (INIS)

    Seefelder, W.; Humpf, H.-U.; Schwerdt, G.; Freudinger, R.; Gekle, M.

    2003-01-01

    Fumonisin B 1 (FB 1 ) causes apoptosis in a variety of cell types and tissues but the apoptotic potential of other fumonisins and fumonisin metabolites has not been determined and the underlying mechanisms are not completely understood. In our studies we exposed human proximal tubule-derived cells (IHKE cells) to FB 1 , fumonisin B 2 (FB 2 ), fumonisin B 3 (FB 3 ), hydrolyzed fumonisin B 1 (HFB 1 ) and N-palmitoyl-hydrolyzed fumonisin B 1 (N-Pal-HFB 1 ) and investigated caspase-3 activation, chromatin condensation and DNA fragmentation. Exposure to 10 μmol/L FB 1 for 24 h led to a significant increase in caspase-3 activity, chromatin condensation and to DNA fragmentation. All other tested compounds did not show any significant activation of caspase-3 activity nor chromatin condensation and DNA-fragmentation. Furthermore, we examined if a sphinganine accumulation is correlated with an induction of apoptosis in IHKE cells. Therefore we used a liquid chromatography/electrospray ionization-mass spectrometry(LC/ESI-MS)-method using phytosphingosine as an internal standard to determine sphinganine and sphingosine concentrations in IHKE cells. Whereas a significant increase of sphinganine (up to 7000% compared to control cells) was observed with all fumonisin-derivates, sphingosine levels nearly remained unchanged indicating that all substrates inhibited ceramide synthase effectively. These results demonstrate that all compounds let to increased sphinganine levels in IHKE cells but only FB 1 was able to induce apoptosis. We conclude that the inhibition of the ceramide synthase is not per se a predictor whether or not fumonisins induce apoptosis

  12. Network class superposition analyses.

    Directory of Open Access Journals (Sweden)

    Carl A B Pearson

    Full Text Available Networks are often used to understand a whole system by modeling the interactions among its pieces. Examples include biomolecules in a cell interacting to provide some primary function, or species in an environment forming a stable community. However, these interactions are often unknown; instead, the pieces' dynamic states are known, and network structure must be inferred. Because observed function may be explained by many different networks (e.g., ≈ 10(30 for the yeast cell cycle process, considering dynamics beyond this primary function means picking a single network or suitable sample: measuring over all networks exhibiting the primary function is computationally infeasible. We circumvent that obstacle by calculating the network class ensemble. We represent the ensemble by a stochastic matrix T, which is a transition-by-transition superposition of the system dynamics for each member of the class. We present concrete results for T derived from boolean time series dynamics on networks obeying the Strong Inhibition rule, by applying T to several traditional questions about network dynamics. We show that the distribution of the number of point attractors can be accurately estimated with T. We show how to generate Derrida plots based on T. We show that T-based Shannon entropy outperforms other methods at selecting experiments to further narrow the network structure. We also outline an experimental test of predictions based on T. We motivate all of these results in terms of a popular molecular biology boolean network model for the yeast cell cycle, but the methods and analyses we introduce are general. We conclude with open questions for T, for example, application to other models, computational considerations when scaling up to larger systems, and other potential analyses.

  13. Forging T-Lymphocyte Identity: Intersecting Networks of Transcriptional Control.

    Science.gov (United States)

    Rothenberg, Ellen V; Ungerbäck, Jonas; Champhekar, Ameya

    2016-01-01

    T-lymphocyte development branches off from other lymphoid developmental programs through its requirement for sustained environmental signals through the Notch pathway. In the thymus, Notch signaling induces a succession of T-lineage regulatory factors that collectively create the T-cell identity through distinct steps. This process involves both the staged activation of T-cell identity genes and the staged repression of progenitor-cell-inherited regulatory genes once their roles in self-renewal and population expansion are no longer needed. With the recent characterization of innate lymphoid cells (ILCs) that share transcriptional regulation programs extensively with T-cell subsets, T-cell identity can increasingly be seen as defined in modular terms, as the processes selecting and actuating effector function are potentially detachable from the processes generating and selecting clonally unique T-cell receptor structures. The developmental pathways of different classes of T cells and ILCs are distinguished by the numbers of prerequisites of gene rearrangement, selection, and antigen contact before the cells gain access to nearly common regulatory mechanisms for choosing effector function. Here, the major classes of transcription factors that interact with Notch signals during T-lineage specification are discussed in terms of their roles in these programs, the evidence for their spectra of target genes at different stages, and their cross-regulatory and cooperative actions with each other. Specific topics include Notch modulation of PU.1 and GATA-3, PU.1-Notch competition, the relationship between PU.1 and GATA-3, and the roles of E proteins, Bcl11b, and GATA-3 in guiding acquisition of T-cell identity while avoiding redirection to an ILC fate. © 2016 Elsevier Inc. All rights reserved.

  14. A hybridised variable neighbourhood tabu search heuristic to increase security in a utility network

    International Nuclear Information System (INIS)

    Janssens, Jochen; Talarico, Luca; Sörensen, Kenneth

    2016-01-01

    We propose a decision model aimed at increasing security in a utility network (e.g., electricity, gas, water or communication network). The network is modelled as a graph, the edges of which are unreliable. We assume that all edges (e.g., pipes, cables) have a certain, not necessarily equal, probability of failure, which can be reduced by selecting edge-specific security strategies. We develop a mathematical programming model and a metaheuristic approach that uses a greedy random adaptive search procedure to find an initial solution and uses tabu search hybridised with iterated local search and a variable neighbourhood descend heuristic to improve this solution. The main goal is to reduce the risk of service failure between an origin and a destination node by selecting the right combination of security measures for each network edge given a limited security budget. - Highlights: • A decision model aimed at increasing security in a utility network is proposed. • The goal is to reduce the risk of service failure given a limited security budget. • An exact approach and a variable neighbourhood tabu search heuristic are developed. • A generator for realistic networks is built and used to test the solution methods. • The hybridised heuristic reduces the total risk on average with 32%.

  15. Identification of a Dynamic Core Transcriptional Network in t(8;21 AML that Regulates Differentiation Block and Self-Renewal

    Directory of Open Access Journals (Sweden)

    Anetta Ptasinska

    2014-09-01

    Full Text Available Oncogenic transcription factors such as RUNX1/ETO, which is generated by the chromosomal translocation t(8;21, subvert normal blood cell development by impairing differentiation and driving malignant self-renewal. Here, we use digital footprinting and chromatin immunoprecipitation sequencing (ChIP-seq to identify the core RUNX1/ETO-responsive transcriptional network of t(8;21 cells. We show that the transcriptional program underlying leukemic propagation is regulated by a dynamic equilibrium between RUNX1/ETO and RUNX1 complexes, which bind to identical DNA sites in a mutually exclusive fashion. Perturbation of this equilibrium in t(8;21 cells by RUNX1/ETO depletion leads to a global redistribution of transcription factor complexes within preexisting open chromatin, resulting in the formation of a transcriptional network that drives myeloid differentiation. Our work demonstrates on a genome-wide level that the extent of impaired myeloid differentiation in t(8;21 is controlled by the dynamic balance between RUNX1/ETO and RUNX1 activities through the repression of transcription factors that drive differentiation.

  16. Chronic exposure to water pollutant trichloroethylene increased epigenetic drift in CD4(+) T cells.

    Science.gov (United States)

    Gilbert, Kathleen M; Blossom, Sarah J; Erickson, Stephen W; Reisfeld, Brad; Zurlinden, Todd J; Broadfoot, Brannon; West, Kirk; Bai, Shasha; Cooney, Craig A

    2016-05-01

    Autoimmune disease and CD4(+) T-cell alterations are induced in mice exposed to the water pollutant trichloroethylene (TCE). We examined here whether TCE altered gene-specific DNA methylation in CD4(+) T cells as a possible mechanism of immunotoxicity. Naive and effector/memory CD4(+) T cells from mice exposed to TCE (0.5 mg/ml in drinking water) for 40 weeks were examined by bisulfite next-generation DNA sequencing. A probabilistic model calculated from multiple genes showed that TCE decreased methylation control in CD4(+) T cells. Data from individual genes fitted to a quadratic regression model showed that TCE increased gene-specific methylation variance in both CD4 subsets. TCE increased epigenetic drift of specific CpG sites in CD4(+) T cells.

  17. Interactions between default mode and control networks as a function of increasing cognitive reasoning complexity.

    Science.gov (United States)

    Hearne, Luke; Cocchi, Luca; Zalesky, Andrew; Mattingley, Jason B

    2015-07-01

    Successful performance of challenging cognitive tasks depends on a consistent functional segregation of activity within the default-mode network, on the one hand, and control networks encompassing frontoparietal and cingulo-opercular areas on the other. Recent work, however, has suggested that in some cognitive control contexts nodes within the default-mode and control networks may actually cooperate to achieve optimal task performance. Here, we used functional magnetic resonance imaging to examine whether the ability to relate variables while solving a cognitive reasoning problem involves transient increases in connectivity between default-mode and control regions. Participants performed a modified version of the classic Wason selection task, in which the number of variables to be related is systematically varied across trials. As expected, areas within the default-mode network showed a parametric deactivation with increases in relational complexity, compared with neural activity in null trials. Critically, some of these areas also showed enhanced connectivity with task-positive control regions. Specifically, task-based connectivity between the striatum and the angular gyri, and between the thalamus and right temporal pole, increased as a function of relational complexity. These findings challenge the notion that functional segregation between regions within default-mode and control networks invariably support cognitive task performance, and reveal previously unknown roles for the striatum and thalamus in managing network dynamics during cognitive reasoning. © 2015 Wiley Periodicals, Inc.

  18. Increasing the safety and efficacy of chimeric antigen receptor T cell therapy

    Directory of Open Access Journals (Sweden)

    Hua Li

    2017-04-01

    Full Text Available Abstract Chimeric antigen receptor (CAR T cell therapy is a promising cancer treatment that has recently been undergoing rapid development. However, there are still some major challenges, including precise tumor targeting to avoid off-target or “on-target/off-tumor” toxicity, adequate T cell infiltration and migration to solid tumors and T cell proliferation and persistence across the physical and biochemical barriers of solid tumors. In this review, we focus on the primary challenges and strategies to design safe and effective CAR T cells, including using novel cutting-edge technologies for CAR and vector designs to increase both the safety and efficacy, further T cell modification to overcome the tumor-associated immune suppression, and using gene editing technologies to generate universal CAR T cells. All these efforts promote the development and evolution of CAR T cell therapy and move toward our ultimate goal—curing cancer with high safety, high efficacy, and low cost.

  19. An Empirical Approach Towards Zero Energy Networks (ZEN)

    NARCIS (Netherlands)

    Tamma, V.P.

    2012-01-01

    Information and Communication Technology (ICT) is changing the way we live and has become an essential part of our life. With the advent of Internet of Things (IoT), and Wireless Sensor Networks (WSN) in particular, the number of devices that are networked is increasing exponentially over the years.

  20. Proposal to endorse the award of a contract for the supply of a juniper T320 network router

    CERN Document Server

    2003-01-01

    This document concerns the award of a contract for the supply of a JUNIPER T320 Network Router. The Finance Committee is invited to endorse the CERN Management's decision to negotiate a contract with QWEST COMMUNICATION (USA) for the supply of a JUNIPER T320 Network Router for a total amount not exceeding 265 000 US dollars (350 000 Swiss francs). The Finance Committee is also requested to approve the negotiation of a maintenance contract for a value not exceeding 50 000 US dollars (66 000 Swiss francs) for three years and the option to purchase additional network interfaces for a value not exceeding 100 000 US dollars (132 000 Swiss francs) bringing the total amount to 415 000 US dollars (548 000 Swiss francs), not subject to revision. CERN's contribution will not exceed 90 000 Swiss francs. The amounts in Swiss francs have been calculated using the present rate of exchange. The firm has indicated the following distribution by country of the contract value covered by this adjudication proposal: CA - 100%.

  1. Luminal and basolateral uptake of insulin in isolated perfused, proximal tubules

    International Nuclear Information System (INIS)

    Nielsen, S.; Nielsen, J.T.; Christensen, E.I.

    1987-01-01

    The present study was performed to quantitate compare the luminal and the peritubular uptake of 125 I-insulin in isolated, perfused, proximal tubules from rabbit kidneys. 125 I-insulin was added in physiological concentrations to either the perfusate or the bath fluid for 30 min. The luminal uptake in 30 min averaged 0.76 pg/mm at physiological concentrations and 18.0 pg/mm at high insulin concentrations. About 15-41% of the absorbed insulin was digested and 125 I-insulin at physiological and high concentrations in the bath was 0.136 and 0.318 pg, respectively. The data indicates that insulin is bound/absorbed at the basolateral membranes both by a saturable specific mechanism and a nonspecific, nonsaturable mechanism. The basolateral absorption constituted 15.2 and 1.8% of the total tubular extraction of insulin at physiological and high insulin concentrations, respectively. Electron microscope autoradiography showed that, after luminal as well as basolateral endocytosis, insulin was exclusively accumulated in endocytic vacuoles and lysosomes

  2. 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

  3. Human‐Centric IoT Networks

    DEFF Research Database (Denmark)

    Mihovska, Albena Dimitrova; Prasad, Ramjee; Pejanovic, Milica

    2017-01-01

    The current Internet of things (IoT) concept is characterized with billions and billions of devices interworking through a myriad of technologies for the delivery of smart personalized services and applications. At the center of these is the human user who drives his/her own interconnected cluster....... This concept has also been introduced elsewhere as “human center sensing (HCS).” The vision pushed by the authors of this chapter for the IoT beyond 2050 is one of the large‐scale and dense HCS connectivities, the complexity of which can be used to extract new IoT value proposition....

  4. Chronic exposure to water pollutant trichloroethylene increased epigenetic drift in CD4+ T cells

    Science.gov (United States)

    Gilbert, Kathleen M; Blossom, Sarah J; Erickson, Stephen W; Reisfeld, Brad; Zurlinden, Todd J; Broadfoot, Brannon; West, Kirk; Bai, Shasha; Cooney, Craig A

    2016-01-01

    Aim: Autoimmune disease and CD4+ T-cell alterations are induced in mice exposed to the water pollutant trichloroethylene (TCE). We examined here whether TCE altered gene-specific DNA methylation in CD4+ T cells as a possible mechanism of immunotoxicity. Materials & methods: Naive and effector/memory CD4+ T cells from mice exposed to TCE (0.5 mg/ml in drinking water) for 40 weeks were examined by bisulfite next-generation DNA sequencing. Results: A probabilistic model calculated from multiple genes showed that TCE decreased methylation control in CD4+ T cells. Data from individual genes fitted to a quadratic regression model showed that TCE increased gene-specific methylation variance in both CD4 subsets. Conclusion: TCE increased epigenetic drift of specific CpG sites in CD4+ T cells. PMID:27092578

  5. Frontline Science: Functionally impaired geriatric CAR-T cells rescued by increased α5β1 integrin expression.

    Science.gov (United States)

    Guha, Prajna; Cunetta, Marissa; Somasundar, Ponnandai; Espat, N Joseph; Junghans, Richard P; Katz, Steven C

    2017-08-01

    Chimeric antigen receptor expressing T cells (CAR-T) are a promising form of immunotherapy, but the influence of age-related immune changes on CAR-T production remains poorly understood. We showed that CAR-T cells from geriatric donors (gCAR-T) are functionally impaired relative to CAR-T from younger donors (yCAR-T). Higher transduction efficiencies and improved cell expansion were observed in yCAR-T cells compared with gCAR-T. yCAR-T demonstrated significantly increased levels of proliferation and signaling activation of phosphorylated (p)Erk, pAkt, pStat3, and pStat5. Furthermore, yCAR-T contained higher proportions of CD4 and CD8 effector memory (EM) cells, which are known to have enhanced cytolytic capabilities. Accordingly, yCAR-T demonstrated higher levels of tumor antigen-specific cytotoxicity compared with gCAR-T. Enhanced tumor killing by yCAR-T correlated with increased levels of perforin and granzyme B. yCAR-T had increased α5β1 integrin expression, a known mediator of retroviral transduction. We found that treatment with M-CSF or TGF-β1 rescued the impaired transduction efficiency of the gCAR-T by increasing the α5β1 integrin expression. Neutralization of α5β1 confirmed that this integrin was indispensable for CAR expression. Our study suggests that the increase of α5β1 integrin expression levels enhances CAR expression and thereby improves tumor killing by gCAR-T. © Society for Leukocyte Biology.

  6. A network biology approach evaluating the anticancer effects of bortezomib identifies SPARC as a therapeutic target in adult T-cell leukemia cells

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2008-10-01

    Full Text Available Junko H Ohyashiki1, Ryoko Hamamura2, Chiaki Kobayashi2, Yu Zhang2, Kazuma Ohyashiki21Intractable Immune System Disease Research Center, Tokyo Medical University, Tokyo, Japan; 2First Department of Internal Medicine, Tokyo Medical University, Tokyo, JapanAbstract: There is a need to identify the regulatory gene interaction of anticancer drugs on target cancer cells. Whole genome expression profiling offers promise in this regard, but can be complicated by the challenge of identifying the genes affected by hundreds to thousands of genes that induce changes in expression. A proteasome inhibitor, bortezomib, could be a potential therapeutic agent in treating adult T-cell leukemia (ATL patients, however, the underlying mechanism by which bortezomib induces cell death in ATL cells via gene regulatory network has not been fully elucidated. Here we show that a Bayesian statistical framework by VoyaGene® identified a secreted protein acidic and rich in cysteine (SPARC gene, a tumor-invasiveness related gene, as a possible modulator of bortezomib-induced cell death in ATL cells. Functional analysis using RNAi experiments revealed that inhibition of the expression SPARC by siRNA enhanced the apoptotic effect of bortezomib on ATL cells in accordance with an increase of cleaved caspase 3. Targeting SPARC may help to treat ATL patients in combination with bortezomib. This work shows that a network biology approach can be used advantageously to identify the genetic interaction related to anticancer effects.Keywords: network biology, adult T cell leukemia, bortezomib, SPARC

  7. Optimization of Cognitive Radio Secondary Information Gathering Station Positioning and Operating Channel Selection for IoT Sensor Networks

    Directory of Open Access Journals (Sweden)

    Jinyi Wen

    2018-01-01

    Full Text Available The Internet of Things (IoT is the interconnection of different objects through the internet using different communication technologies. The objects are equipped with sensors and communications modules. The cognitive radio network is a key technique for the IoT and can effectively address spectrum-related issues for IoT applications. In our paper, a novel method for IoT sensor networks is proposed to obtain the optimal positions of secondary information gathering stations (SIGSs and to select the optimal operating channel. Our objective is to maximize secondary system capacity while protecting the primary system. In addition, we propose an appearance probability matrix for secondary IoT devices (SIDs to maximize the supportable number of SIDs that can be installed in a car, in wearable devices, or for other monitoring devices, based on optimal deployment and probability. We derive fitness functions based on the above objectives and also consider signal to interference-plus-noise ratio (SINR and position constraints. The particle swarm optimization (PSO technique is used to find the best position and operating channel for the SIGSs. In a simulation study, the performance of the proposed method is evaluated and compared with a random resources allocation algorithm (parts of this paper were presented at the ICTC2017 conference (Wen et al., 2017.

  8. Networking: You Can't Do It Alone, But....

    Science.gov (United States)

    Fley, JoAnn

    1986-01-01

    Discusses how networking provides an effective means of learning about one's environment and of gaining help and support in improving it. The process of networking is examined through case studies. The difference between networking and organizing is also discussed. (CT)

  9. Frequent Surfing on Social Health Networks is Associated With Increased Knowledge and Patient Health Activation.

    Science.gov (United States)

    Grosberg, Dafna; Grinvald, Haya; Reuveni, Haim; Magnezi, Racheli

    2016-08-10

    The advent of the Internet has driven a technological revolution that has changed our lives. As part of this phenomenon, social networks have attained a prominent role in health care. A variety of medical services is provided over the Internet, including home monitoring, interactive communications between the patient and service providers, and social support, among others. This study emphasizes some of the practical implications of Web-based health social networks for patients and for health care systems. The objective of this study was to assess how participation in a social network among individuals with a chronic condition contributed to patient activation, based on the Patient Activation Measure (PAM). A prospective, cross-sectional survey with a retrospective component was conducted. Data were collected from Camoni, a Hebrew-language Web-based social health network, participants in the diabetes mellitus, pain, hypertension, and depression/anxiety forums, during November 2012 to 2013. Experienced users (enrolled at least 6 months) and newly enrolled received similar versions of the same questionnaire including sociodemographics and PAM. Among 686 participants, 154 of 337 experienced and 123 of 349 newly enrolled completed the questionnaire. Positive correlations (Psocial relationships, and chronic disease knowledge. Men surfed longer than women (χ²3=10.104, Psocial health network use were correlated with increased knowledge about a chronic disease. Experienced surfers had higher PAM than newly enrolled, suggesting that continued site use may contribute to increased activation. Web-based social health networks offer an opportunity to expand patient knowledge and increase involvement in personal health, thereby increasing patient activation. Further studies are needed to examine these changes on other aspects of chronic illnesses such as quality of life and costs.

  10. Protein-protein networks construction and their relevance measurement based on multi-epitope-ligand-kartographie and gene ontology data of T-cell surface proteins for polymyositis.

    Science.gov (United States)

    Li, Fang-Zhen; Gao, Feng

    2012-08-01

    Polymyositis is an inflammatory myopathy characterized by muscle invasion of T-cells penetrating the basal lamina and displacing the plasma membrane of normal muscle fibers. In order to understand the different adhesive mechanisms at the T-cell surface, Schubert randomly selected 19 proteins expressed at the T-cell surface and studied them using MELK technique [4], among which 15 proteins are picked up for further study by us. Two types of functional similarity networks are constructed for these proteins. The first type is MELK similarity network, which is constructed based on their MELK data by using the McNemar's test [24]. The second type is GO similarity network, which is constructed based on their GO annotation data by using the RSS method to measuring functional similarity. Then the subset surprisology theory is employed to measure the degree of similarity between two networks. Our computing results show that these two types of networks are high related. This conclusion added new values on MELK technique and expanded its applications greatly.

  11. Regulation of renal Na+-K-ATPase in the rat: role of increased potassium transport

    International Nuclear Information System (INIS)

    Mujais, S.K.; Chekal, M.A.; Hayslett, J.P.; Katz, A.I.

    1986-01-01

    The purpose of this study was to characterize the alterations in collecting tubule Na + -K + -ATPase activity produced by sustained increments in dietary potassium in the rat and to evaluate the role of aldosterone in their generation. In adrenal-intact animals, feeding a high-potassium diet or administration of a high physiological dose of aldosterone, which simulates the delivery rate of this hormone during potassium loading, caused marked increments in Na + -K + -ATPase activity in the cortical collecting tubule (CCT) but had no effect on the enzyme in the inner stripe of the medullary collecting tubule (MCT). A significant increase in enzyme activity was also observed after smaller dietary potassium increments and after 4 days of dietary potassium load. In adrenalectomized rats provided with physiological replacement doses of corticosterone and aldosterone, Na + -K + -ATPase activity in both CCT and MCT was similar to that of adrenal-intact controls but remained unchanged after 7 days on the potassium-enriched (10-fold) diet. In contrast, adrenalectomized animals receiving the high physiological dose of aldosterone displayed an increase in Na + -K + -ATPase activity of CCT comparable with that of adrenal-intact animals, whereas the enzyme activity in the MCT was unaffected. In conclusion, 1) following chronic potassium loading Na + -K + -ATPase activity increases significantly in the CCT with no change in its activity in the inner stripe of the MCT; 2) this increase in enzyme activity occurs in a time-dependent fashion and in proportion to the potassium load; and 3) the stimulation of Na + -K + -ATPase activity in adrenal-replaced rats is facilitated by augmented levels of aldosterone, such as those actually observed in adrenal-intact rats subjected to chronic potassium loading

  12. Regulation of renal Na -K-ATPase in the rat: role of increased potassium transport

    Energy Technology Data Exchange (ETDEWEB)

    Mujais, S.K.; Chekal, M.A.; Hayslett, J.P.; Katz, A.I.

    1986-08-01

    The purpose of this study was to characterize the alterations in collecting tubule Na -K -ATPase activity produced by sustained increments in dietary potassium in the rat and to evaluate the role of aldosterone in their generation. In adrenal-intact animals, feeding a high-potassium diet or administration of a high physiological dose of aldosterone, which simulates the delivery rate of this hormone during potassium loading, caused marked increments in Na -K -ATPase activity in the cortical collecting tubule (CCT) but had no effect on the enzyme in the inner stripe of the medullary collecting tubule (MCT). A significant increase in enzyme activity was also observed after smaller dietary potassium increments and after 4 days of dietary potassium load. In adrenalectomized rats provided with physiological replacement doses of corticosterone and aldosterone, Na -K -ATPase activity in both CCT and MCT was similar to that of adrenal-intact controls but remained unchanged after 7 days on the potassium-enriched (10-fold) diet. In contrast, adrenalectomized animals receiving the high physiological dose of aldosterone displayed an increase in Na -K -ATPase activity of CCT comparable with that of adrenal-intact animals, whereas the enzyme activity in the MCT was unaffected. In conclusion, 1) following chronic potassium loading Na -K -ATPase activity increases significantly in the CCT with no change in its activity in the inner stripe of the MCT; 2) this increase in enzyme activity occurs in a time-dependent fashion and in proportion to the potassium load; and 3) the stimulation of Na -K -ATPase activity in adrenal-replaced rats is facilitated by augmented levels of aldosterone, such as those actually observed in adrenal-intact rats subjected to chronic potassium loading.

  13. Triangulation positioning system network

    Directory of Open Access Journals (Sweden)

    Sfendourakis Marios

    2017-01-01

    Full Text Available This paper presents ongoing work on localization and positioning through triangulation procedure for a Fixed Sensors Network - FSN.The FSN has to work as a system.As the triangulation problem becomes high complicated in a case with large numbers of sensors and transmitters, an adequate grid topology is needed in order to tackle the detection complexity.For that reason a Network grid topology is presented and areas that are problematic and need further analysis are analyzed.The Network System in order to deal with problems of saturation and False Triangulations - FTRNs will have to find adequate methods in every sub-area of the Area Of Interest - AOI.Also, concepts like Sensor blindness and overall Network blindness, are presented. All these concepts affect the Network detection rate and its performance and ought to be considered in a way that the network overall performance won’t be degraded.Network performance should be monitored contentiously, with right algorithms and methods.It is also shown that as the number of TRNs and FTRNs is increased Detection Complexity - DC is increased.It is hoped that with further research all the characteristics of a triangulation system network for positioning will be gained and the system will be able to perform autonomously with a high detection rate.

  14. Harsh corporal punishment is associated with increased T2 relaxation time in dopamine-rich regions.

    Science.gov (United States)

    Sheu, Yi-Shin; Polcari, Ann; Anderson, Carl M; Teicher, Martin H

    2010-11-01

    Harsh corporal punishment (HCP) was defined as frequent parental administration of corporal punishment (CP) for discipline, with occasional use of objects such as straps, or paddles. CP is linked to increased risk for depression and substance abuse. We examine whether long-term exposure to HCP acts as sub-traumatic stressor that contributes to brain alterations, particularly in dopaminergic pathways, which may mediate their increased vulnerability to drug and alcohol abuse. Nineteen young adults who experienced early HCP but no other forms of maltreatment and twenty-three comparable controls were studied. T2 relaxation time (T2-RT) measurements were performed with an echo planar imaging TE stepping technique and T2 maps were calculated and analyzed voxel-by-voxel to locate regional T2-RT differences between groups. Previous studies indicated that T2-RT provides an indirect index of resting cerebral blood volume. Region of interest (ROI) analyses were also conducted in caudate, putamen, nucleus accumbens, anterior cingulate cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus and cerebellar hemispheres. Voxel-based relaxometry showed that HCP was associated with increased T2-RT in right caudate and putamen. ROI analyses also revealed increased T2-RT in dorsolateral prefrontal cortex, substantia nigra, thalamus and accumbens but not globus pallidus or cerebellum. There were significant associations between T2-RT measures in dopamine target regions and use of drugs and alcohol, and memory performance. Alteration in the paramagnetic or hemodynamic properties of dopaminergic cell body and projection regions were observed in subjects with HCP, and these findings may relate to their increased risk for drug and alcohol abuse. Copyright 2010 Elsevier Inc. All rights reserved.

  15. Genetic effect of MTHFR C677T polymorphism on the structural covariance network and white-matter integrity in Alzheimer's disease.

    Science.gov (United States)

    Chang, Yu-Tzu; Hsu, Shih-Wei; Tsai, Shih-Jen; Chang, Ya-Ting; Huang, Chi-Wei; Liu, Mu-En; Chen, Nai-Ching; Chang, Wen-Neng; Hsu, Jung-Lung; Lee, Chen-Chang; Chang, Chiung-Chih

    2017-06-01

    The 677 C to T transition in the MTHFR gene is a genetic determinant for hyperhomocysteinemia. We investigated whether this polymorphism modulates gray matter (GM) structural covariance networks independently of white-matter integrity in patients with Alzheimer's disease (AD). GM structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed-based analysis. The patients were divided into two genotype groups: C homozygotes (n = 73) and T carriers (n = 62). Using diffusion tensor imaging and white-matter parcellation, 11 fiber bundle integrities were compared between the two genotype groups. Cognitive test scores were the major outcome factors. The T carriers had higher homocysteine levels, lower posterior cingulate cortex GM volume, and more clusters in the dorsal medial lobe subsystem showing stronger covariance strength. Both posterior cingulate cortex seed and interconnected peak cluster volumes predicted cognitive test scores, especially in the T carriers. There were no between-group differences in fiber tract diffusion parameters. The MTHFR 677T polymorphism modulates posterior cingulate cortex-anchored structural covariance strength independently of white matter integrities. Hum Brain Mapp 38:3039-3051, 2017. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc.

  16. Increasing Scalability of Researcher Network Extraction from the Web

    Science.gov (United States)

    Asada, Yohei; Matsuo, Yutaka; Ishizuka, Mitsuru

    Social networks, which describe relations among people or organizations as a network, have recently attracted attention. With the help of a social network, we can analyze the structure of a community and thereby promote efficient communications within it. We investigate the problem of extracting a network of researchers from the Web, to assist efficient cooperation among researchers. Our method uses a search engine to get the cooccurences of names of two researchers and calculates the streangth of the relation between them. Then we label the relation by analyzing the Web pages in which these two names cooccur. Research on social network extraction using search engines as ours, is attracting attention in Japan as well as abroad. However, the former approaches issue too many queries to search engines to extract a large-scale network. In this paper, we propose a method to filter superfluous queries and facilitates the extraction of large-scale networks. By this method we are able to extract a network of around 3000-nodes. Our experimental results show that the proposed method reduces the number of queries significantly while preserving the quality of the network as compared to former methods.

  17. Induction of apoptosis in cultured human proximal tubule cells by fumonisins and fumonisin metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Seefelder, W; Humpf, H -U; Schwerdt, G; Freudinger, R; Gekle, M

    2003-10-15

    Fumonisin B{sub 1} (FB{sub 1}) causes apoptosis in a variety of cell types and tissues but the apoptotic potential of other fumonisins and fumonisin metabolites has not been determined and the underlying mechanisms are not completely understood. In our studies we exposed human proximal tubule-derived cells (IHKE cells) to FB{sub 1}, fumonisin B{sub 2} (FB{sub 2}), fumonisin B{sub 3} (FB{sub 3}), hydrolyzed fumonisin B{sub 1} (HFB{sub 1}) and N-palmitoyl-hydrolyzed fumonisin B{sub 1} (N-Pal-HFB{sub 1}) and investigated caspase-3 activation, chromatin condensation and DNA fragmentation. Exposure to 10 {mu}mol/L FB{sub 1} for 24 h led to a significant increase in caspase-3 activity, chromatin condensation and to DNA fragmentation. All other tested compounds did not show any significant activation of caspase-3 activity nor chromatin condensation and DNA-fragmentation. Furthermore, we examined if a sphinganine accumulation is correlated with an induction of apoptosis in IHKE cells. Therefore we used a liquid chromatography/electrospray ionization-mass spectrometry(LC/ESI-MS)-method using phytosphingosine as an internal standard to determine sphinganine and sphingosine concentrations in IHKE cells. Whereas a significant increase of sphinganine (up to 7000% compared to control cells) was observed with all fumonisin-derivates, sphingosine levels nearly remained unchanged indicating that all substrates inhibited ceramide synthase effectively. These results demonstrate that all compounds let to increased sphinganine levels in IHKE cells but only FB{sub 1} was able to induce apoptosis. We conclude that the inhibition of the ceramide synthase is not per se a predictor whether or not fumonisins induce apoptosis.

  18. Human kidney proximal tubule cells are vulnerable to the effects of Rauwolfia serpentina.

    Science.gov (United States)

    Mossoba, Miriam E; Flynn, Thomas J; Vohra, Sanah; Wiesenfeld, Paddy L; Sprando, Robert L

    2015-12-01

    Rauwolfia serpentina (or Snake root plant) is a botanical dietary supplement marketed in the USA for maintaining blood pressure. Very few studies have addressed the safety of this herb, despite its wide availability to consumers. Its reported pleiotropic effects underscore the necessity for evaluating its safety. We used a human kidney cell line to investigate the possible negative effects of R. serpentina on the renal system in vitro, with a specific focus on the renal proximal tubules. We evaluated cellular and mitochondrial toxicity, along with a variety of other kidney-specific toxicology biomarkers. We found that R. serpentina was capable of producing highly detrimental effects in our in vitro renal cell system. These results suggest more studies are needed to investigate the safety of this dietary supplement in both kidney and other target organ systems.

  19. FlnA binding to PACSIN2 F-BAR domain regulates membrane tubulation in megakaryocytes and platelets.

    Science.gov (United States)

    Begonja, Antonija Jurak; Pluthero, Fred G; Suphamungmee, Worawit; Giannini, Silvia; Christensen, Hilary; Leung, Richard; Lo, Richard W; Nakamura, Fumihiko; Lehman, William; Plomann, Markus; Hoffmeister, Karin M; Kahr, Walter H A; Hartwig, John H; Falet, Hervé

    2015-07-02

    Bin-Amphiphysin-Rvs (BAR) and Fes-CIP4 homology BAR (F-BAR) proteins generate tubular membrane invaginations reminiscent of the megakaryocyte (MK) demarcation membrane system (DMS), which provides membranes necessary for future platelets. The F-BAR protein PACSIN2 is one of the most abundant BAR/F-BAR proteins in platelets and the only one reported to interact with the cytoskeletal and scaffold protein filamin A (FlnA), an essential regulator of platelet formation and function. The FlnA-PACSIN2 interaction was therefore investigated in MKs and platelets. PACSIN2 associated with FlnA in human platelets. The interaction required FlnA immunoglobulin-like repeat 20 and the tip of PACSIN2 F-BAR domain and enhanced PACSIN2 F-BAR domain membrane tubulation in vitro. Most human and wild-type mouse platelets had 1 to 2 distinct PACSIN2 foci associated with cell membrane GPIbα, whereas Flna-null platelets had 0 to 4 or more foci. Endogenous PACSIN2 and transfected enhanced green fluorescent protein-PACSIN2 were concentrated in midstage wild-type mouse MKs in a well-defined invagination of the plasma membrane reminiscent of the initiating DMS and dispersed in the absence of FlnA binding. The DMS appeared less well defined, and platelet territories were not readily visualized in Flna-null MKs. We conclude that the FlnA-PACSIN2 interaction regulates membrane tubulation in MKs and platelets and likely contributes to DMS formation. © 2015 by The American Society of Hematology.

  20. Secure Communications in CIoT Networks with a Wireless Energy Harvesting Untrusted Relay.

    Science.gov (United States)

    Hu, Hequn; Gao, Zhenzhen; Liao, Xuewen; Leung, Victor C M

    2017-09-04

    The Internet of Things (IoT) represents a bright prospect that a variety of common appliances can connect to one another, as well as with the rest of the Internet, to vastly improve our lives. Unique communication and security challenges have been brought out by the limited hardware, low-complexity, and severe energy constraints of IoT devices. In addition, a severe spectrum scarcity problem has also been stimulated by the use of a large number of IoT devices. In this paper, cognitive IoT (CIoT) is considered where an IoT network works as the secondary system using underlay spectrum sharing. A wireless energy harvesting (EH) node is used as a relay to improve the coverage of an IoT device. However, the relay could be a potential eavesdropper to intercept the IoT device's messages. This paper considers the problem of secure communication between the IoT device (e.g., sensor) and a destination (e.g., controller) via the wireless EH untrusted relay. Since the destination can be equipped with adequate energy supply, secure schemes based on destination-aided jamming are proposed based on power splitting (PS) and time splitting (TS) policies, called intuitive secure schemes based on PS (Int-PS), precoded secure scheme based on PS (Pre-PS), intuitive secure scheme based on TS (Int-TS) and precoded secure scheme based on TS (Pre-TS), respectively. The secure performances of the proposed schemes are evaluated through the metric of probability of successfully secure transmission ( P S S T ), which represents the probability that the interference constraint of the primary user is satisfied and the secrecy rate is positive. P S S T is analyzed for the proposed secure schemes, and the closed form expressions of P S S T for Pre-PS and Pre-TS are derived and validated through simulation results. Numerical results show that the precoded secure schemes have better P S S T than the intuitive secure schemes under similar power consumption. When the secure schemes based on PS and TS

  1. Umbilical Cord Blood-Derived Mononuclear Cells Exhibit Pericyte-Like Phenotype and Support Network Formation of Endothelial Progenitor Cells In Vitro.

    Science.gov (United States)

    Peters, Erica B; Liu, Betty; Christoforou, Nicolas; West, Jennifer L; Truskey, George A

    2015-10-01

    Umbilical cord blood represents a promising cell source for pro-angiogenic therapies. The present study examined the potential of mononuclear cells (MNCs) from umbilical cord blood to support endothelial progenitor cell (EPC) microvessel formation. MNCs were isolated from the cord blood of 20 separate donors and selected for further characterization based upon their proliferation potential and morphological resemblance to human vascular pericytes (HVPs). MNCs were screened for their ability to support EPC network formation using an in vitro assay (Matrigel™) as well as a reductionist, coculture system consisting of no additional angiogenic cytokines beyond those present in serum. In less than 15% of the isolations, we identified a population of highly proliferative MNCs that phenotypically resembled HVPs as assessed by expression of PDGFR-β, NG2, α-SMA, and ephrin-B2. Within a Matrigel™ system, MNCs demonstrated pericyte-like function through colocalization to EPC networks and similar effects as HVPs upon total EPC tubule length (p = 0.95) and number of branch points (p = 0.93). In a reductionist coculture system, MNCs served as pro-angiogenic mural cells by supporting EPC network formation to a significantly greater extent than HVP cocultures, by day 14 of coculture, as evidenced through EPC total tubule length (p < 0.0001) and number of branch points (p < 0.0001). Our findings are significant as we demonstrate mural cell progenitors can be isolated from umbilical cord blood and develop culture conditions to support their use in microvascular tissue engineering applications.

  2. T-S Fuzzy Model Based Control Strategy for the Networked Suspension Control System of Maglev Train

    Directory of Open Access Journals (Sweden)

    Guang He

    2015-01-01

    Full Text Available The control problem for the networked suspension control system of maglev train with random induced time delay and packet dropouts is investigated. First, Takagi-Sugeno (T-S fuzzy models are utilized to represent the discrete-time nonlinear networked suspension control system, and the parameters uncertainties of the nonlinear model have also been taken into account. The controllers take the form of parallel distributed compensation. Then, a sufficient condition for the stability of the networked suspension control system is derived. Based on the criteria, the state feedback fuzzy controllers are obtained, and the controller gains can be computed by using MATLAB LMI Toolbox directly. Finally, both the numerical simulations and physical experiments on the full-scale single bogie of CMS-04 maglev train have been accomplished to demonstrate the effectiveness of this proposed method.

  3. CD8+ Tumor-Infiltrating T Cells Are Trapped in the Tumor-Dendritic Cell Network

    Directory of Open Access Journals (Sweden)

    Alexandre Boissonnas

    2013-01-01

    Full Text Available Chemotherapy enhances the antitumor adaptive immune T cell response, but the immunosuppressive tumor environment often dominates, resulting in cancer relapse. Antigen-presenting cells such as tumor-associated macrophages (TAMs and tumor dendritic cells (TuDCs are the main protagonists of tumor-infiltrating lymphocyte (TIL immuno-suppression. TAMs have been widely investigated and are associated with poor prognosis, but the immuno-suppressive activity of TuDCs is less well understood. We performed two-photon imaging of the tumor tissue to examine the spatiotemporal interactions between TILs and TuDCs after chemotherapy. In a strongly immuno-suppressive murine tumor model, cyclophosphamide-mediated chemotherapy transiently enhanced the antitumor activity of adoptively transferred ovalbumin-specific CD8+ T cell receptor transgenic T cells (OTI but barely affected TuDC compartment within the tumor. Time lapse imaging of living tumor tissue showed that TuDCs are organized as a mesh with dynamic interconnections. Once infiltrated into the tumor parenchyma, OTI T cells make antigen-specific and long-lasting contacts with TuDCs. Extensive analysis of TIL infiltration on histologic section revealed that after chemotherapy the majority of OTI T cells interact with TuDCs and that infiltration is restricted to TuDC-rich areas. We propose that the TuDC network exerts antigen-dependent unproductive retention that trap T cells and limit their antitumor effectiveness.

  4. Effects of phospho- and calciotropic hormones on electrolyte transport in the proximal tubule [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Justin J. Lee

    2017-10-01

    Full Text Available Calcium and phosphate are critical for a myriad of physiological and cellular processes within the organism. Consequently, plasma levels of calcium and phosphate are tightly regulated. This occurs through the combined effects of the phospho- and calciotropic hormones, parathyroid hormone (PTH, active vitamin D3, and fibroblast growth factor 23 (FGF23. The organs central to this are the kidneys, intestine, and bone. In the kidney, the proximal tubule reabsorbs the majority of filtered calcium and phosphate, which amounts to more than 60% and 90%, respectively. The basic molecular mechanisms responsible for phosphate reclamation are well described, and emerging work is delineating the molecular identity of the paracellular shunt wherein calcium permeates the proximal tubular epithelium. Significant experimental work has delineated the molecular effects of PTH and FGF23 on these processes as well as their regulation of active vitamin D3 synthesis in this nephron segment. The integrative effects of both phospho- and calciotropic hormones on proximal tubular solute transport and subsequently whole body calcium-phosphate balance thus have been further complicated. Here, we first review the molecular mechanisms of calcium and phosphate reabsorption from the proximal tubule and how they are influenced by the phospho- and calciotropic hormones acting on this segment and then consider the implications on both renal calcium and phosphate handling as well as whole body mineral balance.

  5. Research on Fault Diagnosis for Pumping Station Based on T-S Fuzzy Fault Tree and Bayesian Network

    Directory of Open Access Journals (Sweden)

    Zhuqing Bi

    2017-01-01

    Full Text Available According to the characteristics of fault diagnosis for pumping station, such as the complex structure, multiple mappings, and numerous uncertainties, a new approach combining T-S fuzzy gate fault tree and Bayesian network (BN is proposed. On the one hand, traditional fault tree method needs the logical relationship between events and probability value of events and can only represent the events with two states. T-S fuzzy gate fault tree method can solve these disadvantages but still has weaknesses in complex reasoning and only one-way reasoning. On the other hand, the BN is suitable for fault diagnosis of pumping station because of its powerful ability to deal with uncertain information. However, it is difficult to determine the structure and conditional probability tables of the BN. Therefore, the proposed method integrates the advantages of the two methods. Finally, the feasibility of the method is verified through a fault diagnosis model of the rotor in the pumping unit, the accuracy of the method is verified by comparing with the methods based on traditional Bayesian network and BP neural network, respectively, when the historical data is sufficient, and the results are more superior to the above two when the historical data is insufficient.

  6. INCREASING RELIABILITY OF STEPPED AUTOMATIC STARTING AND RHEOSTAT BREAKING SYSTEM OF ELECTRIC TRAINS ER9T AND EPL9T

    Directory of Open Access Journals (Sweden)

    N. H. Visin

    2010-06-01

    Full Text Available The article examines transitional processes in the power circuit of tractive motors and their influence on the work of stepped automatic starting of electric trains ER9T and EPL9T. The recommendations for increasing the reliability of operation of multiple-unit rolling stock are proposed.

  7. Elevated Expression of GlpT and UhpT via FNR Activation Contributes to Increased Fosfomycin Susceptibility in Escherichia coli under Anaerobic Conditions

    Science.gov (United States)

    Kurabayashi, Kumiko; Tanimoto, Koichi; Fueki, Shinobu; Tomita, Haruyoshi

    2015-01-01

    Because a shortage of new antimicrobial agents is a critical issue at present, and with the spread of multidrug-resistant (MDR) pathogens, the use of fosfomycin to treat infections is being revisited as a “last-resort option.” This drug offers a particular benefit in that it is more effective against bacteria growing under oxygen-limited conditions, unlike other commonly used antimicrobials, such as fluoroquinolones and aminoglycosides. In this study, we showed that Escherichia coli strains, including enterohemorrhagic E. coli (EHEC), were more susceptible to fosfomycin when grown anaerobically than when grown aerobically, and we investigated how the activity of this drug was enhanced during anaerobic growth of E. coli. Our quantitative PCR analysis and a transport assay showed that E. coli cells grown under anaerobic conditions had higher levels of expression of glpT and uhpT, encoding proteins that transport fosfomycin into cells with their native substrates, i.e., glycerol-3-phosphate and glucose-6-phosphate, and led to increased intracellular accumulation of the drug. Elevation of expression of these genes during anaerobic growth requires FNR, a global transcriptional regulator that is activated under anaerobic conditions. Purified FNR bound to DNA fragments from regions upstream of glpT and uhpT, suggesting that it is an activator of expression of glpT and uhpT during anaerobic growth. We concluded that the increased antibacterial activity of fosfomycin toward E. coli under anaerobic conditions can be attributed to elevated expression of GlpT and UhpT following activation of FNR, leading to increased uptake of the drug. PMID:26248376

  8. An increase in tobacco craving is associated with enhanced medial prefrontal cortex network coupling.

    Directory of Open Access Journals (Sweden)

    Amy C Janes

    Full Text Available Craving is a key aspect of drug dependence that is thought to motivate continued drug use. Numerous brain regions have been associated with craving, suggesting that craving is mediated by a distributed brain network. Whether an increase in subjective craving is associated with enhanced interactions among brain regions was evaluated using resting state functional magnetic imaging (fMRI in nicotine dependent participants. We focused on craving-related changes in the orbital and medial prefrontal cortex (OMPFC network, which also included the subgenual anterior cingulate cortex (sgACC extending into the ventral striatum. Brain regions in the OMPFC network are not only implicated in addiction and reward, but, due to their rich anatomic interconnections, may serve as the site of integration across craving-related brain regions. Subjective craving and resting state fMRI were evaluated twice with an ∼1 hour delay between the scans. Cigarette craving was significantly increased at the end, relative to the beginning of the scan session. Enhanced craving was associated with heightened coupling between the OMPFC network and other cortical, limbic, striatal, and visceromotor brain regions that are both anatomically interconnected with the OMPFC, and have been implicated in addiction and craving. This is the first demonstration confirming that an increase in craving is associated with enhanced brain region interactions, which may play a role in the experience of craving.

  9. Anti-correlations in the degree distribution increase stimulus detection performance in noisy spiking neural networks.

    Science.gov (United States)

    Martens, Marijn B; Houweling, Arthur R; E Tiesinga, Paul H

    2017-02-01

    Neuronal circuits in the rodent barrel cortex are characterized by stable low firing rates. However, recent experiments show that short spike trains elicited by electrical stimulation in single neurons can induce behavioral responses. Hence, the underlying neural networks provide stability against internal fluctuations in the firing rate, while simultaneously making the circuits sensitive to small external perturbations. Here we studied whether stability and sensitivity are affected by the connectivity structure in recurrently connected spiking networks. We found that anti-correlation between the number of afferent (in-degree) and efferent (out-degree) synaptic connections of neurons increases stability against pathological bursting, relative to networks where the degrees were either positively correlated or uncorrelated. In the stable network state, stimulation of a few cells could lead to a detectable change in the firing rate. To quantify the ability of networks to detect the stimulation, we used a receiver operating characteristic (ROC) analysis. For a given level of background noise, networks with anti-correlated degrees displayed the lowest false positive rates, and consequently had the highest stimulus detection performance. We propose that anti-correlation in the degree distribution may be a computational strategy employed by sensory cortices to increase the detectability of external stimuli. We show that networks with anti-correlated degrees can in principle be formed by applying learning rules comprised of a combination of spike-timing dependent plasticity, homeostatic plasticity and pruning to networks with uncorrelated degrees. To test our prediction we suggest a novel experimental method to estimate correlations in the degree distribution.

  10. Why a Central Network Position Isn't Enough

    DEFF Research Database (Denmark)

    Reinholt, Mia; Pedersen, Torben; Foss, Nicolai Juul

    2011-01-01

    in such networks. This problem may, however, be resolved by including motivation and ability to share knowledge as moderators of the association between network position and knowledge sharing. Our analysis of 705 employees in a consultancy shows that employees’ knowledge acquisition and provision are highest when...... network centrality, autonomous motivation, and ability are all high, thus supporting the proposed three-way interaction....

  11. Increased T2 signal intensity in the distal clavicle: incidence and clinical implications

    International Nuclear Information System (INIS)

    Fiorella, D.; Helms, C.A.; Speer, K.P.

    2000-01-01

    Objective. The objectives of the current study were (1) to quantify the incidence of increased T2 signal in the distal clavicle and (2) to assess the clinical significance of this finding in patients with chronic acromioclavicular (AC) joint pain.Design and patients. Eight patients (five male and three female, 15-41 years of age) with disabling shoulder pain localized to the AC joint and marked increased T2 signal in the distal clavicle are presented. These eight patients underwent MR examination over a 25 month period (August 1996 to September 1998). The dictated reports of all shoulder MR examinations conducted over this same time period were reviewed retrospectively for the presence of signal abnormality in the distal cla-vicle. Clinical data and, in five patients, findings at shoulder arthroscopy or open surgery, were correlated with the results of MR imaging. One patient underwent arthroscopy on both shoulders.Results. The selected eight patients each presented clinically with disabling shoulder pain localized to the AC joint. One patient is presented twice, as both shoulders were symptomatic (n=9). Plain film examination (9/9) failed to indicate a structural cause of shoulder pain in any of the patients. MR examination demonstrated abnormally increased T2 signal in the distal clavicle in all nine cases and no other cause for AC joint pain. Three patients responded to a course of conservative therapy. Six experienced refractory pain despite conservative therapy. Resection of the distal clavicle was performed in five of the six cases. All patients who underwent resection of the distal clavicle experienced complete resolution of AC joint pain. A retrospective review of the dictated reports for all shoulder MR imaging examinations performed at out institution over a 25 month period (August 1996 to September 1998; n=761) demonstrated a 12.5% incidence of abnormally increased T2 signal in the distal clav-icle.Conclusions. Increased T2 signal in the distal clavicle

  12. Increased T2 signal intensity in the distal clavicle: incidence and clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Fiorella, D.; Helms, C.A. [Dept. of Radiology, Duke Univ., Durham, NC (United States); Speer, K.P. [Dept. of Orthopedic Surgery, Duke Univ., Durham, NC (United States)

    2000-12-01

    Objective. The objectives of the current study were (1) to quantify the incidence of increased T2 signal in the distal clavicle and (2) to assess the clinical significance of this finding in patients with chronic acromioclavicular (AC) joint pain.Design and patients. Eight patients (five male and three female, 15-41 years of age) with disabling shoulder pain localized to the AC joint and marked increased T2 signal in the distal clavicle are presented. These eight patients underwent MR examination over a 25 month period (August 1996 to September 1998). The dictated reports of all shoulder MR examinations conducted over this same time period were reviewed retrospectively for the presence of signal abnormality in the distal cla-vicle. Clinical data and, in five patients, findings at shoulder arthroscopy or open surgery, were correlated with the results of MR imaging. One patient underwent arthroscopy on both shoulders.Results. The selected eight patients each presented clinically with disabling shoulder pain localized to the AC joint. One patient is presented twice, as both shoulders were symptomatic (n=9). Plain film examination (9/9) failed to indicate a structural cause of shoulder pain in any of the patients. MR examination demonstrated abnormally increased T2 signal in the distal clavicle in all nine cases and no other cause for AC joint pain. Three patients responded to a course of conservative therapy. Six experienced refractory pain despite conservative therapy. Resection of the distal clavicle was performed in five of the six cases. All patients who underwent resection of the distal clavicle experienced complete resolution of AC joint pain. A retrospective review of the dictated reports for all shoulder MR imaging examinations performed at out institution over a 25 month period (August 1996 to September 1998; n=761) demonstrated a 12.5% incidence of abnormally increased T2 signal in the distal clav-icle.Conclusions. Increased T2 signal in the distal clavicle

  13. Project W.A.T.E.R.

    Science.gov (United States)

    EnviroTeach, 1992

    1992-01-01

    Introduces networking projects for studying rivers and water quality. Describes two projects in South Africa (Project W.A.T.E.R and SWAP) associated with the international network, Global Rivers Environmental Education Network. Discusses water test kits and educational material developed through Project W.A.T.E.R. (Water Awareness through…

  14. Network Interface Specification for the T1 Microprocessor

    Science.gov (United States)

    1994-05-01

    details of the data transfer functional units, interconnect structure, and network operation. Application Layer Communication Model Communication...use of the communication resources. 3.6 Network Virtualisation The CNS-1 is designed for single-user, batch-style processing; no timesharing or space...matches the count register (both the timer and count register are in the network interface and are user-accessible). Although this function is not strictly

  15. Leveraging modern climatology to increase adaptive capacity across protected area networks

    Science.gov (United States)

    Davison, J.E.; Graumlich, L.J.; Rowland, E.L.; Pederson, G.T.; Breshears, D.D.

    2012-01-01

    Human-driven changes in the global environment pose an increasingly urgent challenge for the management of ecosystems that is made all the more difficult by the uncertain future of both environmental conditions and ecological responses. Land managers need strategies to increase regional adaptive capacity, but relevant and rapid assessment approaches are lacking. To address this need, we developed a method to assess regional protected area networks across biophysically important climatic gradients often linked to biodiversity and ecosystem function. We plot the land of the southwestern United States across axes of historical climate space, and identify landscapes that may serve as strategic additions to current protected area portfolios. Considering climate space is straightforward, and it can be applied using a variety of relevant climate parameters across differing levels of land protection status. The resulting maps identify lands that are climatically distinct from existing protected areas, and may be utilized in combination with other ecological and socio-economic information essential to collaborative landscape-scale decision-making. Alongside other strategies intended to protect species of special concern, natural resources, and other ecosystem services, the methods presented herein provide another important hedging strategy intended to increase the adaptive capacity of protected area networks. ?? 2011 Elsevier Ltd.

  16. O(t-α)-synchronization and Mittag-Leffler synchronization for the fractional-order memristive neural networks with delays and discontinuous neuron activations.

    Science.gov (United States)

    Chen, Jiejie; Chen, Boshan; Zeng, Zhigang

    2018-04-01

    This paper investigates O(t -α )-synchronization and adaptive Mittag-Leffler synchronization for the fractional-order memristive neural networks with delays and discontinuous neuron activations. Firstly, based on the framework of Filippov solution and differential inclusion theory, using a Razumikhin-type method, some sufficient conditions ensuring the global O(t -α )-synchronization of considered networks are established via a linear-type discontinuous control. Next, a new fractional differential inequality is established and two new discontinuous adaptive controller is designed to achieve Mittag-Leffler synchronization between the drive system and the response systems using this inequality. Finally, two numerical simulations are given to show the effectiveness of the theoretical results. Our approach and theoretical results have a leading significance in the design of synchronized fractional-order memristive neural networks circuits involving discontinuous activations and time-varying delays. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. An Auction-Based Spectrum Leasing Mechanism for Mobile Macro-Femtocell Networks of IoT.

    Science.gov (United States)

    Chen, Xin; Xing, Lei; Qiu, Tie; Li, Zhuo

    2017-02-16

    The Internet of Things (IoT) is a vision of the upcoming society. It can provide pervasive communication between two or more entities using 4G-LTE (Long Term Evolution) communication technology. In 4G-LTE networks, there are two important problems: helping manage the spectrum demands of IoT devices and achieving much more revenue with the limited resource. This paper proposes a pricing framework to investigate the spectrum leasing in mobile heterogeneous networks with single macrocell and multiple femtocells. We modeled the leasing procedure between the macrocell service provider (MSP) and femtocell holders (FHs) as an auction to motivate the MSP to lease its spectrum resource. All FHs act as the bidders, and the monopolist MSP acts as the auctioneer. In the auction, FHs submit their bids to rent the spectrum resource so that they can make a profit by selling it to their subscribers. The MSP determines the spectrum leasing amount and chooses the winning FHs by solving the dynamic programming-based 0-1 knapsack problem. In our proposed framework, we focus on the spectrum pricing strategy and revenue maximization of the MSP. The simulation results show that the proposed scheme provides effective motivation for the MSP to lease the spectrum to FHs, and both the MSP and FHs can benefit from spectrum leasing.

  18. An Auction-Based Spectrum Leasing Mechanism for Mobile Macro-Femtocell Networks of IoT

    Directory of Open Access Journals (Sweden)

    Xin Chen

    2017-02-01

    Full Text Available The Internet of Things (IoT is a vision of the upcoming society. It can provide pervasive communication between two or more entities using 4G-LTE (Long Term Evolution communication technology. In 4G-LTE networks, there are two important problems: helping manage the spectrum demands of IoT devices and achieving much more revenue with the limited resource. This paper proposes a pricing framework to investigate the spectrum leasing in mobile heterogeneous networks with single macrocell and multiple femtocells. We modeled the leasing procedure between the macrocell service provider (MSP and femtocell holders (FHs as an auction to motivate the MSP to lease its spectrum resource. All FHs act as the bidders, and the monopolist MSP acts as the auctioneer. In the auction, FHs submit their bids to rent the spectrum resource so that they can make a profit by selling it to their subscribers. The MSP determines the spectrum leasing amount and chooses the winning FHs by solving the dynamic programming-based 0–1 knapsack problem. In our proposed framework, we focus on the spectrum pricing strategy and revenue maximization of the MSP. The simulation results show that the proposed scheme provides effective motivation for the MSP to lease the spectrum to FHs, and both the MSP and FHs can benefit from spectrum leasing.

  19. Meditation is associated with increased brain network integration.

    Science.gov (United States)

    van Lutterveld, Remko; van Dellen, Edwin; Pal, Prasanta; Yang, Hua; Stam, Cornelis Jan; Brewer, Judson

    2017-09-01

    This study aims to identify novel quantitative EEG measures associated with mindfulness meditation. As there is some evidence that meditation is associated with higher integration of brain networks, we focused on EEG measures of network integration. Sixteen novice meditators and sixteen experienced meditators participated in the study. Novice meditators performed a basic meditation practice that supported effortless awareness, which is an important quality of experience related to mindfulness practices, while their EEG was recorded. Experienced meditators performed a self-selected meditation practice that supported effortless awareness. Network integration was analyzed with maximum betweenness centrality and leaf fraction (which both correlate positively with network integration) as well as with diameter and average eccentricity (which both correlate negatively with network integration), based on a phase-lag index (PLI) and minimum spanning tree (MST) approach. Differences between groups were assessed using repeated-measures ANOVA for the theta (4-8 Hz), alpha (8-13 Hz) and lower beta (13-20 Hz) frequency bands. Maximum betweenness centrality was significantly higher in experienced meditators than in novices (P = 0.012) in the alpha band. In the same frequency band, leaf fraction showed a trend toward being significantly higher in experienced meditators than in novices (P = 0.056), while diameter and average eccentricity were significantly lower in experienced meditators than in novices (P = 0.016 and P = 0.028 respectively). No significant differences between groups were observed for the theta and beta frequency bands. These results show that alpha band functional network topology is better integrated in experienced meditators than in novice meditators during meditation. This novel finding provides the rationale to investigate the temporal relation between measures of functional connectivity network integration and meditation quality, for example using

  20. PROTOCOLS FOR INCREASING THE LIFETIME OF NODES OF AD HOC WIRELESS NETWORKS

    Directory of Open Access Journals (Sweden)

    B.Malarkodi

    2010-03-01

    Full Text Available Power consumption of nodes in ad hoc networks is a critical issue as they predominantly operate on batteries. In order to improve the lifetime of an ad hoc network, all the nodes must be utilized evenly and the power required for connections must be minimized. Energy management deals with the process of managing energy resources by means of controlling the battery discharge, adjusting the transmission power and scheduling of power sources so as to increase the lifetime of the nodes of an ad hoc wireless network. In this paper, two protocols are proposed to improve the lifetime of the nodes. The first protocol assumes smart battery packages with L cells and uses dynamic programming (DP to optimally select the set of cells used to satisfy a request for power. The second one proposes a MAC layer protocol denoted as Power Aware medium Access Control (PAMAC protocol which enables the network layer to select a route with minimum total power requirement among the possible routes between a source and a destination provided all nodes in the routes have battery capacity above a threshold. The life time of the nodes using the DP based scheduling policy is found through simulation and compared with that obtained using the techniques reported in the literature. It is found that DP based policy increases the lifetime of the mobile nodes by a factor of 1.15 to 1.8. The life expectancy, the average power consumption and throughput of the network using PAMAC protocol are computed through simulation and compared with that of the other MAC layer protocols 802.11, MACA, and CSMA. Besides this, the life expectancy and average power consumption of the network for different values of threshold are also compared. From the simulation results, it is observed that PAMAC consumes the least power and provides the longest lifetime among the various MAC Layer protocols. Moreover, using PAMAC as the MAC layer protocol, the performance obtained using different routing layer

  1. Effects of phospho- and calciotropic hormones on electrolyte transport in the proximal tubule

    DEFF Research Database (Denmark)

    Lee, Justin J; Plain, Allein; Beggs, Megan R

    2017-01-01

    ), active vitamin D 3, and fibroblast growth factor 23 (FGF23). The organs central to this are the kidneys, intestine, and bone. In the kidney, the proximal tubule reabsorbs the majority of filtered calcium and phosphate, which amounts to more than 60% and 90%, respectively. The basic molecular mechanisms......Calcium and phosphate are critical for a myriad of physiological and cellular processes within the organism. Consequently, plasma levels of calcium and phosphate are tightly regulated. This occurs through the combined effects of the phospho- and calciotropic hormones, parathyroid hormone (PTH...... as their regulation of active vitamin D 3 synthesis in this nephron segment. The integrative effects of both phospho- and calciotropic hormones on proximal tubular solute transport and subsequently whole body calcium-phosphate balance thus have been further complicated. Here, we first review the molecular mechanisms...

  2. Drawing Inspiration from Human Brain Networks: Construction of Interconnected Virtual Networks.

    Science.gov (United States)

    Murakami, Masaya; Kominami, Daichi; Leibnitz, Kenji; Murata, Masayuki

    2018-04-08

    Virtualization of wireless sensor networks (WSN) is widely considered as a foundational block of edge/fog computing, which is a key technology that can help realize next-generation Internet of things (IoT) networks. In such scenarios, multiple IoT devices and service modules will be virtually deployed and interconnected over the Internet. Moreover, application services are expected to be more sophisticated and complex, thereby increasing the number of modifications required for the construction of network topologies. Therefore, it is imperative to establish a method for constructing a virtualized WSN (VWSN) topology that achieves low latency on information transmission and high resilience against network failures, while keeping the topological construction cost low. In this study, we draw inspiration from inter-modular connectivity in human brain networks, which achieves high performance when dealing with large-scale networks composed of a large number of modules (i.e., regions) and nodes (i.e., neurons). We propose a method for assigning inter-modular links based on a connectivity model observed in the cerebral cortex of the brain, known as the exponential distance rule (EDR) model. We then choose endpoint nodes of these links by controlling inter-modular assortativity, which characterizes the topological connectivity of brain networks. We test our proposed methods using simulation experiments. The results show that the proposed method based on the EDR model can construct a VWSN topology with an optimal combination of communication efficiency, robustness, and construction cost. Regarding the selection of endpoint nodes for the inter-modular links, the results also show that high assortativity enhances the robustness and communication efficiency because of the existence of inter-modular links of two high-degree nodes.

  3. Drawing Inspiration from Human Brain Networks: Construction of Interconnected Virtual Networks

    Directory of Open Access Journals (Sweden)

    Masaya Murakami

    2018-04-01

    Full Text Available Virtualization of wireless sensor networks (WSN is widely considered as a foundational block of edge/fog computing, which is a key technology that can help realize next-generation Internet of things (IoT networks. In such scenarios, multiple IoT devices and service modules will be virtually deployed and interconnected over the Internet. Moreover, application services are expected to be more sophisticated and complex, thereby increasing the number of modifications required for the construction of network topologies. Therefore, it is imperative to establish a method for constructing a virtualized WSN (VWSN topology that achieves low latency on information transmission and high resilience against network failures, while keeping the topological construction cost low. In this study, we draw inspiration from inter-modular connectivity in human brain networks, which achieves high performance when dealing with large-scale networks composed of a large number of modules (i.e., regions and nodes (i.e., neurons. We propose a method for assigning inter-modular links based on a connectivity model observed in the cerebral cortex of the brain, known as the exponential distance rule (EDR model. We then choose endpoint nodes of these links by controlling inter-modular assortativity, which characterizes the topological connectivity of brain networks. We test our proposed methods using simulation experiments. The results show that the proposed method based on the EDR model can construct a VWSN topology with an optimal combination of communication efficiency, robustness, and construction cost. Regarding the selection of endpoint nodes for the inter-modular links, the results also show that high assortativity enhances the robustness and communication efficiency because of the existence of inter-modular links of two high-degree nodes.

  4. PL/SQL and Bind Variable: the two ways to increase the efficiency of Network Databases

    Directory of Open Access Journals (Sweden)

    Hitesh KUMAR SHARMA

    2011-12-01

    Full Text Available Modern data analysis applications are driven by the Network databases. They are pushing traditional database and data warehousing technologies beyond their limits due to their massively increasing data volumes and demands for low latency. There are three major challenges in working with network databases: interoperability due to heterogeneous data repositories, proactively due to autonomy of data sources and high efficiency to meet the application demand. This paper provides the two ways to meet the third challenge of network databases. This goal can be achieved by network database administrator with the usage of PL/SQL blocks and bind variable. The paper will explain the effect of PL/SQL block and bind variable on Network database efficiency to meet the modern data analysis application demand.

  5. Narcolepsy Type 1 Is Associated with a Systemic Increase and Activation of Regulatory T Cells and with a Systemic Activation of Global T Cells.

    Science.gov (United States)

    Lecendreux, Michel; Churlaud, Guillaume; Pitoiset, Fabien; Regnault, Armelle; Tran, Tu Anh; Liblau, Roland; Klatzmann, David; Rosenzwajg, Michelle

    2017-01-01

    Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1) has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination. The goal of this study was to compare peripheral blood immune cell populations in recent onset pediatric NT1 subjects (post or non-post 2009-influenza A H1N1 vaccination) to healthy donors. We demonstrated an increased number of central memory CD4+ T cells (CD62L+ CD45RA-) associated to an activated phenotype (increase in CD69 and CD25 expression) in NT1 patients. Percentage and absolute count of regulatory T cells (Tregs) in NT1 patients were increased associated with an activated phenotype (increase in GITR and LAP expression), and of activated memory phenotype. Cytokine production by CD4+ and CD8+ T cells after activation was not modified in NT1 patients. In H1N1 vaccinated NT1 patients, absolute counts of CD3+, CD8+ T cells, and B cells were increased compared to non-vaccinated NT1 patients. These results support a global T cell activation in NT1 patients and thus support a T cell-mediated autoimmune origin of NT1, but do not demonstrate the pathological role of H1N1 prophylactic vaccination. They should prompt further studies of T cells, particularly of Tregs (such as suppression and proliferation antigen specific assays, and also T-cell receptor sequencing), in NT1.

  6. Nuclear power plant transient diagnostics using artificial neural networks that allow ''don't-know'' classifications

    International Nuclear Information System (INIS)

    Bartal, Y.; Lin, J.; Uhrig, R.E.

    1995-01-01

    A nuclear power plant's (NPP's) status is usually monitored by a human operator. Any classifier system used to enhance the operator's capability to diagnose a safety-critical system like an NPP should classify a novel transient as ''don't-know'' if it is not contained within its accumulated knowledge base. In particular, the classifier needs some kind of proximity measure between the new data and its training set. Artificial neural networks have been proposed as NPP classifiers, the most popular ones being the multilayered perceptron (MLP) type. However, MLPs do not have a proximity measure, while learning vector quantization, probabilistic neural networks (PNNs), and some others do. This proximity measure may also serve as an explanation to the classifier's decision in the way that case-based-reasoning expert systems do. The capability of a PNN network as a classifier is demonstrated using simulator data for the three-loop 436-MW(electric) Westinghouse San Onofre unit 1 pressurized water reactor. A transient's classification history is used in an ''evidence accumulation'' technique to enhance a classifier's accuracy as well as its consistency

  7. Differential patterns of injury to the proximal tubule of renal cortical slices following in vitro exposure to mercuric chloride, potassium dichromate, or hypoxic conditions.

    Science.gov (United States)

    Ruegg, C E; Gandolfi, A J; Nagle, R B; Brendel, K

    1987-09-15

    The innate susceptibility of renal cell types to these agents was investigated using precision-cut rabbit renal cortical slices made perpendicular to the cortical-papillary axis. Slices were incubated in DME/F12 medium containing 10 microM, 100 microM, or 1 mM concentrations of either metal for 12 hr or in Krebs-Hepes buffer gassed with nitrogen (100%) for 0.75 to 5 hr of hypoxic exposure. To simulate postischemic reperfusion, some slices were transferred to vessels gassed with oxygen after an initial hypoxic period. Mercuric chloride (100 microM) exposure resulted in damage to the straight regions of proximal tubules by 12 hr leaving convoluted regions unaffected. Hypoxia (2.25 hr) and potassium dichromate (100 microM for 12 hr) both caused injury to the convoluted proximal tubules without affecting straight proximal tubular regions. Mercury concentrations of 10 microM and 1 mM had no effect or injured all cell types within the slice, respectively. Similar results were observed for hypoxic periods less than 1.5 hr or greater than 3 hr of exposure. Potassium dichromate had no measurable affect at 10 microM, but at 1 mM focal lesions were observed after 4 hr of exposure, and by 12 hr all cell types within the slice were affected. Intracellular potassium content normalized to DNA correlated well, but always preceded the pathological lesions observed. These results demonstrate that injury to specific regions of the proximal tubule by these agents relates to an innate susceptibility of the intoxicated cell type independent of physiologic feedback or blood delivery patterns proposed as mechanisms of selective injury from in vivo studies.

  8. Remote network control plasma diagnostic system for Tokamak T-10

    International Nuclear Information System (INIS)

    Troynov, V I; Zimin, A M; Krupin, V A; Notkin, G E; Nurgaliev, M R

    2016-01-01

    The parameters of molecular plasma in closed magnetic trap is studied in this paper. Using the system of molecular diagnostics, which was designed by the authors on the «Tokamak T-10» facility, the radiation of hydrogen isotopes at the plasma edge is investigated. The scheme of optical radiation registration within visible spectrum is described. For visualization, identification and processing of registered molecular spectra a new software is developed using MatLab environment. The software also includes electronic atlas of electronic-vibrational-rotational transitions for molecules of protium and deuterium. To register radiation from limiter cross-section a network control system is designed using the means of the Internet/Intranet. Remote control system diagram and methods are given. The examples of web-interfaces for working out equipment control scenarios and viewing of results are provided. After test run in Intranet, the remote diagnostic system will be accessible through Internet. (paper)

  9. Mindfulness Meditation Training and Executive Control Network Resting State Functional Connectivity: A Randomized Controlled Trial.

    Science.gov (United States)

    Taren, Adrienne A; Gianaros, Peter J; Greco, Carol M; Lindsay, Emily K; Fairgrieve, April; Brown, Kirk Warren; Rosen, Rhonda K; Ferris, Jennifer L; Julson, Erica; Marsland, Anna L; Creswell, J David

    Mindfulness meditation training has been previously shown to enhance behavioral measures of executive control (e.g., attention, working memory, cognitive control), but the neural mechanisms underlying these improvements are largely unknown. Here, we test whether mindfulness training interventions foster executive control by strengthening functional connections between dorsolateral prefrontal cortex (dlPFC)-a hub of the executive control network-and frontoparietal regions that coordinate executive function. Thirty-five adults with elevated levels of psychological distress participated in a 3-day randomized controlled trial of intensive mindfulness meditation or relaxation training. Participants completed a resting state functional magnetic resonance imaging scan before and after the intervention. We tested whether mindfulness meditation training increased resting state functional connectivity (rsFC) between dlPFC and frontoparietal control network regions. Left dlPFC showed increased connectivity to the right inferior frontal gyrus (T = 3.74), right middle frontal gyrus (MFG) (T = 3.98), right supplementary eye field (T = 4.29), right parietal cortex (T = 4.44), and left middle temporal gyrus (T = 3.97, all p < .05) after mindfulness training relative to the relaxation control. Right dlPFC showed increased connectivity to right MFG (T = 4.97, p < .05). We report that mindfulness training increases rsFC between dlPFC and dorsal network (superior parietal lobule, supplementary eye field, MFG) and ventral network (right IFG, middle temporal/angular gyrus) regions. These findings extend previous work showing increased functional connectivity among brain regions associated with executive function during active meditation by identifying specific neural circuits in which rsFC is enhanced by a mindfulness intervention in individuals with high levels of psychological distress. Clinicaltrials.gov,NCT01628809.

  10. Early Posttransplant Isolated v1 Lesion Does Not Need to Be Treated and Does Not Lead to Increased Fibrosis

    Directory of Open Access Journals (Sweden)

    Irfan Moinuddin

    2016-01-01

    Full Text Available Acute vascular rejection (AVR is characterized by intimal arteritis in addition to tubulitis and interstitial inflammation. It is associated with a poorer prognosis compared to tubulointerstitial rejection (AIR and AVR is associated with a higher rate of graft loss than AIR. The prognosis and treatment of arteritis without tubulitis and interstitial inflammation (isolated v1 lesion are still controversial. We report a case of a patient who had a biopsy of the kidney allograft for evaluation of slow graft function. The biopsy revealed an isolated v1 lesion. However, we chose not to augment immunosuppression. The patient’s kidney allograft function improved over time with close monitoring. Repeat biopsy a year later showed no evidence of endothelialitis and relatively unchanged fibrosis and no other abnormalities. Although it is suggested that most cases of isolated v1 lesions will respond to corticosteroids or T cell depleting therapies, some cases will improve with conservative management. Further studies are needed to determine which cases could be managed conservatively.

  11. Hypoxia inducible factor 1-alpha (HIF-1 alpha is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival.

    Directory of Open Access Journals (Sweden)

    Elisa Conde

    Full Text Available Acute tubular necrosis (ATN caused by ischemia/reperfusion (I/R during renal transplantation delays allograft function. Identification of factors that mediate protection and/or epithelium recovery could help to improve graft outcome. We studied the expression, regulation and role of hypoxia inducible factor 1-alpha (HIF-1 α, using in vitro and in vivo experimental models of I/R as well as human post-transplant renal biopsies. We found that HIF-1 α is stabilized in proximal tubule cells during ischemia and unexpectedly in late reperfusion, when oxygen tension is normal. Both inductions lead to gene expression in vitro and in vivo. In vitro interference of HIF-1 α promoted cell death and in vivo interference exacerbated tissue damage and renal dysfunction. In pos-transplant human biopsies, HIF-1 α was expressed only in proximal tubules which exhibited normal renal structure with a significant negative correlation with ATN grade. In summary, using experimental models and human biopsies, we identified a novel HIF-1 α induction during reperfusion with a potential critical role in renal transplant.

  12. Stochastic Boolean networks: An efficient approach to modeling gene regulatory networks

    Directory of Open Access Journals (Sweden)

    Liang Jinghang

    2012-08-01

    Full Text Available Abstract Background Various computational models have been of interest due to their use in the modelling of gene regulatory networks (GRNs. As a logical model, probabilistic Boolean networks (PBNs consider molecular and genetic noise, so the study of PBNs provides significant insights into the understanding of the dynamics of GRNs. This will ultimately lead to advances in developing therapeutic methods that intervene in the process of disease development and progression. The applications of PBNs, however, are hindered by the complexities involved in the computation of the state transition matrix and the steady-state distribution of a PBN. For a PBN with n genes and N Boolean networks, the complexity to compute the state transition matrix is O(nN22n or O(nN2n for a sparse matrix. Results This paper presents a novel implementation of PBNs based on the notions of stochastic logic and stochastic computation. This stochastic implementation of a PBN is referred to as a stochastic Boolean network (SBN. An SBN provides an accurate and efficient simulation of a PBN without and with random gene perturbation. The state transition matrix is computed in an SBN with a complexity of O(nL2n, where L is a factor related to the stochastic sequence length. Since the minimum sequence length required for obtaining an evaluation accuracy approximately increases in a polynomial order with the number of genes, n, and the number of Boolean networks, N, usually increases exponentially with n, L is typically smaller than N, especially in a network with a large number of genes. Hence, the computational efficiency of an SBN is primarily limited by the number of genes, but not directly by the total possible number of Boolean networks. Furthermore, a time-frame expanded SBN enables an efficient analysis of the steady-state distribution of a PBN. These findings are supported by the simulation results of a simplified p53 network, several randomly generated networks and a

  13. Electrophysiological response of chicken's jejunal epithelium to increasing levels of T-2 toxin.

    Science.gov (United States)

    Yunus, Agha Waqar; Kröger, Susan; Tichy, Alexander; Zentek, Jürgen; Böhm, Josef

    2013-02-01

    The present investigations were conducted to test the effects of T-2 toxin on electrophysiological variables of jejunal epithelium of chicken. Jejunal segments of broilers were monitored in Ussing chambers in the presence of T-2 toxin at the levels of 0 (negative control), 0 (methanol/vehicle control), 0.1, 1, 5, and 10 μg/ml of buffer. T-2 toxin did not affect basal values of short circuit current (I(sc)), transmural potential difference, or tissue conductivity in the jejunal epithelium. T-2 toxin also did not statistically affect glucose-induced electrophysiological variables during the first 3 min of glucose induction. Compared to the vehicle control, the ouabain-sensitive I(sc) was negatively affected (P = 0.008) only under 5 μg of T-2 toxin/ml. Increasing levels of T-2 toxin negatively affected the ouabain-sensitive I(sc) in a cubic (P = 0.007) fashion. These data indicate that acute exposure to moderate levels of T-2 toxin may progressively impair the cation gradient across the jejunal epithelium.

  14. Thermoelectric properties of semiconductor nanowire networks

    Science.gov (United States)

    Roslyak, Oleksiy; Piryatinski, Andrei

    2016-03-01

    To examine the thermoelectric (TE) properties of a semiconductor nanowire (NW) network, we propose a theoretical approach mapping the TE network on a two-port network. In contrast to a conventional single-port (i.e., resistor) network model, our model allows for large scale calculations showing convergence of TE figure of merit, ZT, with an increasing number of junctions. Using this model, numerical simulations are performed for the Bi2Te3 branched nanowire (BNW) and Cayley tree NW (CTNW) network. We find that the phonon scattering at the network junctions plays a dominant role in enhancing the network ZT. Specifically, disordered BNW and CTNW demonstrate an order of magnitude higher ZT enhancement compared to their ordered counterparts. Formation of preferential TE pathways in CTNW makes the network effectively behave as its BNW counterpart. We provide formalism for simulating large scale nanowire networks hinged upon experimentally measurable TE parameters of a single T-junction.

  15. Time and Energy Efficient Relay Transmission for Multi-Hop Wireless Sensor Networks.

    Science.gov (United States)

    Kim, Jin-Woo; Barrado, José Ramón Ramos; Jeon, Dong-Keun

    2016-06-27

    The IEEE 802.15.4 standard is widely recognized as one of the most successful enabling technologies for short range low rate wireless communications and it is used in IoT applications. It covers all the details related to the MAC and PHY layers of the IoT protocol stack. Due to the nature of IoT, the wireless sensor networks are autonomously self-organized networks without infrastructure support. One of the issues in IoT is the network scalability. To address this issue, it is necessary to support the multi-hop topology. The IEEE 802.15.4 network can support a star, peer-to-peer, or cluster-tree topology. One of the IEEE 802.15.4 topologies suited for the high predictability of performance guarantees and energy efficient behavior is a cluster-tree topology where sensor nodes can switch off their transceivers and go into a sleep state to save energy. However, the IEEE 802.15.4 cluster-tree topology may not be able to provide sufficient bandwidth for the increased traffic load and the additional information may not be delivered successfully. The common drawback of the existing approaches is that they do not address the poor bandwidth utilization problem in IEEE 802.15.4 cluster-tree networks, so it is difficult to increase the network performance. Therefore, to solve this problem in this paper we study a relay transmission protocol based on the standard protocol in the IEEE 802.15.4 MAC. In the proposed scheme, the coordinators can relay data frames to their parent devices or their children devices without contention and can provide bandwidth for the increased traffic load or the number of devices. We also evaluate the performance of the proposed scheme through simulation. The simulation results demonstrate that the proposed scheme can improve the reliability, the end-to-end delay, and the energy consumption.

  16. Photonics-oriented data transmission network for the KM3NeT prototype detector

    International Nuclear Information System (INIS)

    Hoek, M. van der; Mos, S.; Schmelling, J.W.; Hogenbirk, J.; Heine, E.; Jansweijer, P.; Kieft, G.; Peek, H.; Timmer, P.; Wolf, E. de; Zwart, A.

    2013-01-01

    The design of the readout and data acquisition system of the future KM3NeT neutrino telescope employs 10 Gbps photonic technologies for data transmission to shore. The photonic architecture can handle standard transmission protocols. The generic scheme is based on DWDM technology using lasers on shore and optical modulators in each of the 12,800 Digital Optical Modules arranged on several hundred vertical detection units anchored to the seabed. Each module will house 31 photomultipliers together with auxiliary instrumentation and readout electronics. A 100 km electro-optical fibre cable will connect the optical modules to the store. The readout system will guarantee an individual optical connection between each optical module and the shore. A small-scale prototype of a detection unit with four optical modules is in a realization phase and will allow for in situ testing of the data transmission network. We will present results of laboratory tests of the photonics-oriented transmission layer of the network that have been realized for the prototype detection unit

  17. Capacity to adapt to environmental change: evidence from a network of organizations concerned with increasing wildfire risk

    Directory of Open Access Journals (Sweden)

    A. Paige. Fischer

    2017-03-01

    Full Text Available Because wildfire size and frequency are expected to increase in many forested areas in the United States, organizations involved in forest and wildfire management could arguably benefit from working together and sharing information to develop strategies for how to adapt to this increasing risk. Social capital theory suggests that actors in cohesive networks are positioned to build trust and mutual understanding of problems and act collectively to address these problems, and that actors engaged with diverse partners are positioned to access new information and resources that are important for innovation and complex problem solving. We investigated the patterns of interaction within a network of organizations involved in forest and wildfire management in Oregon, USA, for evidence of structural conditions that create opportunities for collective action and learning. We used descriptive statistical analysis of social network data gathered through interviews to characterize the structure of the network and exponential random graph modeling to identify key factors in the formation of network ties. We interpreted our findings through the lens of social capital theory to identify implications for the network's capacity to engage in collective action and complex problem-solving about how to adapt to environmental change. We found that tendencies to associate with others with similar management goals, geographic emphases, and attitudes toward wildfire were strong mechanisms shaping network structure, potentially constraining interactions among organizations with diverse information and resources and limiting opportunities for learning and complex problem-solving needed for adaptation. In particular, we found that organizations with fire protection and forest restoration goals comprised distinct networks despite sharing concern about the problem of increasing wildfire risk.

  18. Arabidopsis dynamin-related protein 1A polymers bind, but do not tubulate, liposomes

    International Nuclear Information System (INIS)

    Backues, Steven K.; Bednarek, Sebastian Y.

    2010-01-01

    The Arabidopsis dynamin-related protein 1A (AtDRP1A) is involved in endocytosis and cell plate maturation in Arabidopsis. Unlike dynamin, AtDRP1A does not have any recognized membrane binding or protein-protein interaction domains. We report that GTPase active AtDRP1A purified from Escherichia coli as a fusion to maltose binding protein forms homopolymers visible by negative staining electron microscopy. These polymers interact with protein-free liposomes whose lipid composition mimics that of the inner leaflet of the Arabidopsis plasma membrane, suggesting that lipid-binding may play a role in AtDRP1A function. However, AtDRP1A polymers do not appear to assemble and disassemble in a dynamic fashion and do not have the ability to tubulate liposomes in vitro, suggesting that additional factors or modifications are necessary for AtDRP1A's in vivo function.

  19. Narcolepsy Type 1 Is Associated with a Systemic Increase and Activation of Regulatory T Cells and with a Systemic Activation of Global T Cells.

    Directory of Open Access Journals (Sweden)

    Michel Lecendreux

    Full Text Available Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1 has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (<110 pg/ml. This specific loss of hypocretin and the strong association with the HLA-DQB1*06:02 allele led to the hypothesis that NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination. The goal of this study was to compare peripheral blood immune cell populations in recent onset pediatric NT1 subjects (post or non-post 2009-influenza A H1N1 vaccination to healthy donors. We demonstrated an increased number of central memory CD4+ T cells (CD62L+ CD45RA- associated to an activated phenotype (increase in CD69 and CD25 expression in NT1 patients. Percentage and absolute count of regulatory T cells (Tregs in NT1 patients were increased associated with an activated phenotype (increase in GITR and LAP expression, and of activated memory phenotype. Cytokine production by CD4+ and CD8+ T cells after activation was not modified in NT1 patients. In H1N1 vaccinated NT1 patients, absolute counts of CD3+, CD8+ T cells, and B cells were increased compared to non-vaccinated NT1 patients. These results support a global T cell activation in NT1 patients and thus support a T cell-mediated autoimmune origin of NT1, but do not demonstrate the pathological role of H1N1 prophylactic vaccination. They should prompt further studies of T cells, particularly of Tregs (such as suppression and proliferation antigen specific assays, and also T-cell receptor sequencing, in NT1.

  20. Myosin XI-Dependent Formation of Tubular Structures from Endoplasmic Reticulum Isolated from Tobacco Cultured BY-2 Cells1[W][OA

    Science.gov (United States)

    Yokota, Etsuo; Ueda, Haruko; Hashimoto, Kohsuke; Orii, Hidefumi; Shimada, Tomoo; Hara-Nishimura, Ikuko; Shimmen, Teruo

    2011-01-01

    The reticular network of the endoplasmic reticulum (ER) consists of tubular and lamellar elements and is arranged in the cortical region of plant cells. This network constantly shows shape change and remodeling motion. Tubular ER structures were formed when GTP was added to the ER vesicles isolated from tobacco (Nicotiana tabacum) cultured BY-2 cells expressing ER-localized green fluorescent protein. The hydrolysis of GTP during ER tubule formation was higher than that under conditions in which ER tubule formation was not induced. Furthermore, a shearing force, such as the flow of liquid, was needed for the elongation/extension of the ER tubule. The shearing force was assumed to correspond to the force generated by the actomyosin system in vivo. To confirm this hypothesis, the S12 fraction was prepared, which contained both cytosol and microsome fractions, including two classes of myosins, XI (175-kD myosin) and VIII (BY-2 myosin VIII-1), and ER-localized green fluorescent protein vesicles. The ER tubules and their mesh-like structures were arranged in the S12 fraction efficiently by the addition of ATP, GTP, and exogenous filamentous actin. The tubule formation was significantly inhibited by the depletion of 175-kD myosin from the S12 fraction but not BY-2 myosin VIII-1. Furthermore, a recombinant carboxyl-terminal tail region of 175-kD myosin also suppressed ER tubule formation. The tips of tubules moved along filamentous actin during tubule elongation. These results indicated that the motive force generated by the actomyosin system contributes to the formation of ER tubules, suggesting that myosin XI is responsible not only for the transport of ER in cytoplasm but also for the reticular organization of cortical ER. PMID:21427277

  1. Myosin XI-dependent formation of tubular structures from endoplasmic reticulum isolated from tobacco cultured BY-2 cells.

    Science.gov (United States)

    Yokota, Etsuo; Ueda, Haruko; Hashimoto, Kohsuke; Orii, Hidefumi; Shimada, Tomoo; Hara-Nishimura, Ikuko; Shimmen, Teruo

    2011-05-01

    The reticular network of the endoplasmic reticulum (ER) consists of tubular and lamellar elements and is arranged in the cortical region of plant cells. This network constantly shows shape change and remodeling motion. Tubular ER structures were formed when GTP was added to the ER vesicles isolated from tobacco (Nicotiana tabacum) cultured BY-2 cells expressing ER-localized green fluorescent protein. The hydrolysis of GTP during ER tubule formation was higher than that under conditions in which ER tubule formation was not induced. Furthermore, a shearing force, such as the flow of liquid, was needed for the elongation/extension of the ER tubule. The shearing force was assumed to correspond to the force generated by the actomyosin system in vivo. To confirm this hypothesis, the S12 fraction was prepared, which contained both cytosol and microsome fractions, including two classes of myosins, XI (175-kD myosin) and VIII (BY-2 myosin VIII-1), and ER-localized green fluorescent protein vesicles. The ER tubules and their mesh-like structures were arranged in the S12 fraction efficiently by the addition of ATP, GTP, and exogenous filamentous actin. The tubule formation was significantly inhibited by the depletion of 175-kD myosin from the S12 fraction but not BY-2 myosin VIII-1. Furthermore, a recombinant carboxyl-terminal tail region of 175-kD myosin also suppressed ER tubule formation. The tips of tubules moved along filamentous actin during tubule elongation. These results indicated that the motive force generated by the actomyosin system contributes to the formation of ER tubules, suggesting that myosin XI is responsible not only for the transport of ER in cytoplasm but also for the reticular organization of cortical ER.

  2. Brainstem stimulation increases functional connectivity of basal forebrain-paralimbic network in isoflurane-anesthetized rats.

    Science.gov (United States)

    Pillay, Siveshigan; Liu, Xiping; Baracskay, Péter; Hudetz, Anthony G

    2014-09-01

    Brain states and cognitive-behavioral functions are precisely controlled by subcortical neuromodulatory networks. Manipulating key components of the ascending arousal system (AAS), via deep-brain stimulation, may help facilitate global arousal in anesthetized animals. Here we test the hypothesis that electrical stimulation of the oral part of the pontine reticular nucleus (PnO) under light isoflurane anesthesia, associated with loss of consciousness, leads to cortical desynchronization and specific changes in blood-oxygenation-level-dependent (BOLD) functional connectivity (FC) of the brain. BOLD signals were acquired simultaneously with frontal epidural electroencephalogram before and after PnO stimulation. Whole-brain FC was mapped using correlation analysis with seeds in major centers of the AAS. PnO stimulation produced cortical desynchronization, a decrease in δ- and θ-band power, and an increase in approximate entropy. Significant increases in FC after PnO stimulation occurred between the left nucleus Basalis of Meynert (NBM) as seed and numerous regions of the paralimbic network. Smaller increases in FC were present between the central medial thalamic nucleus and retrosplenium seeds and the left caudate putamen and NBM. The results suggest that, during light anesthesia, PnO stimulation preferentially modulates basal forebrain-paralimbic networks. We speculate that this may be a reflection of disconnected awareness.

  3. Genome-wide network-based pathway analysis of CSF t-tau/Aβ1-42 ratio in the ADNI cohort.

    Science.gov (United States)

    Cong, Wang; Meng, Xianglian; Li, Jin; Zhang, Qiushi; Chen, Feng; Liu, Wenjie; Wang, Ying; Cheng, Sipu; Yao, Xiaohui; Yan, Jingwen; Kim, Sungeun; Saykin, Andrew J; Liang, Hong; Shen, Li

    2017-05-30

    The cerebrospinal fluid (CSF) levels of total tau (t-tau) and Aβ 1-42 are potential early diagnostic markers for probable Alzheimer's disease (AD). The influence of genetic variation on these CSF biomarkers has been investigated in candidate or genome-wide association studies (GWAS). However, the investigation of statistically modest associations in GWAS in the context of biological networks is still an under-explored topic in AD studies. The main objective of this study is to gain further biological insights via the integration of statistical gene associations in AD with physical protein interaction networks. The CSF and genotyping data of 843 study subjects (199 CN, 85 SMC, 239 EMCI, 207 LMCI, 113 AD) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed. PLINK was used to perform GWAS on the t-tau/Aβ 1-42 ratio using quality controlled genotype data, including 563,980 single nucleotide polymorphisms (SNPs), with age, sex and diagnosis as covariates. Gene-level p-values were obtained by VEGAS2. Genes with p-value ≤ 0.05 were mapped on to a protein-protein interaction (PPI) network (9,617 nodes, 39,240 edges, from the HPRD Database). We integrated a consensus model strategy into the iPINBPA network analysis framework, and named it as CM-iPINBPA. Four consensus modules (CMs) were discovered by CM-iPINBPA, and were functionally annotated using the pathway analysis tool Enrichr. The intersection of four CMs forms a common subnetwork of 29 genes, including those related to tau phosphorylation (GSK3B, SUMO1, AKAP5, CALM1 and DLG4), amyloid beta production (CASP8, PIK3R1, PPA1, PARP1, CSNK2A1, NGFR, and RHOA), and AD (BCL3, CFLAR, SMAD1, and HIF1A). This study coupled a consensus module (CM) strategy with the iPINBPA network analysis framework, and applied it to the GWAS of CSF t-tau/Aβ1-42 ratio in an AD study. The genome-wide network analysis yielded 4 enriched CMs that share not only genes related to tau phosphorylation or amyloid beta

  4. Antenatal glucocorticoid treatment alters Na+ uptake in renal proximal tubule cells from adult offspring in a sex-specific manner

    OpenAIRE

    Su, Yixin; Bi, Jianli; Pulgar, Victor M.; Figueroa, Jorge; Chappell, Mark; Rose, James C.

    2015-01-01

    We have shown a sex-specific effect of fetal programming on Na+ excretion in adult sheep. The site of this effect in the kidney is unknown. Therefore, we tested the hypothesis that renal proximal tubule cells (RPTCs) from adult male sheep exposed to betamethasone (Beta) before birth have greater Na+ uptake than do RPTCs from vehicle-exposed male sheep and that RPTCs from female sheep similarly exposed are not influenced by antenatal Beta. In isolated RPTCs from 1- to 1.5-yr-old male and femal...

  5. Potential for increasing conspicuity of short-T1 lesions in the brain using magnetisation transfer imaging

    International Nuclear Information System (INIS)

    De Souza, N.M.; Hajnal, J.V.; Baudouin, C.J.

    1995-01-01

    We investigated the feasibility of using T1-weighted magnetisation transfer sequences to generate tissue contrast and increase the conspicuity of short-T1 areas within the brain. We imaged two normal volunteers with and without saturating off-resonance radiofrequency irradiation at a range of repetition times (TR 200-760 ms). T1 values and magnetisation transfer ratios for white matter and deep grey matter were calculated. We studied eight patients with intracranial lesions showing short-T1 areas, using mildly T1-weighted sequences with and without magnetisation transfer contrast. Lesion numbers, areas and signal intensities were measured and lesion-to-background contrast was calculated. Comparison was made with conventional T1-weighted spin-echo images. In the normal volunteers, contrast between the thalamus, caudate and lentiform nuclei and white matter showed striking visual differences, with magnetisation transfer weighting, with decreasing TR. In all patients, short-T1 lesions were seen more clearly on magnetisation transfer-weighted images, with significant increase in lesion number, area and contrast, when compared with conventional T1-weighted scans. (orig.)

  6. Bifidobacterium breve attenuates murine dextran sodium sulfate-induced colitis and increases regulatory T cell responses.

    Science.gov (United States)

    Zheng, Bin; van Bergenhenegouwen, Jeroen; Overbeek, Saskia; van de Kant, Hendrik J G; Garssen, Johan; Folkerts, Gert; Vos, Paul; Morgan, Mary E; Kraneveld, Aletta D

    2014-01-01

    While some probiotics have shown beneficial effects on preventing or treating colitis development, others have shown no effects. In this study, we have assessed the immunomodulating effects of two probiotic strains, Lactobacillus rhamnosus (L. rhamnosus) and Bifidobacterium breve (B. breve) on T cell polarization in vitro, using human peripheral blood mononuclear cells (PBMC), and in vivo, using murine dextran sodium sulfate (DSS) colitis model. With respect to the latter, the mRNA expression of T cell subset-associated transcription factors and cytokines in the colon was measured and the T helper type (Th) 17 and regulatory T cell (Treg) subsets were determined in the Peyer's patches. Both L. rhamnosus and B. breve incubations in vitro reduced Th17 and increased Th2 cell subsets in human PBMCs. In addition, B. breve incubation was also able to reduce Th1 and increase Treg cell subsets in contrast to L. rhamnosus. In vivo intervention with B. breve, but not L. rhamnosus, significantly attenuated the severity of DSS-induced colitis. In DSS-treated C57BL/6 mice, intervention with B. breve increased the expression of mRNA encoding for Th2- and Treg-associated cytokines in the distal colon. In addition, intervention with B. breve led to increases of Treg and decreases of Th17 cell subsets in Peyer's patches of DSS-treated mice. B. breve modulates T cell polarization towards Th2 and Treg cell-associated responses in vitro and in vivo. In vivo B. breve intervention ameliorates DSS-induced colitis symptoms and this protective effect may mediated by its effects on the T-cell composition.

  7. Bifidobacterium breve attenuates murine dextran sodium sulfate-induced colitis and increases regulatory T cell responses.

    Directory of Open Access Journals (Sweden)

    Bin Zheng

    Full Text Available While some probiotics have shown beneficial effects on preventing or treating colitis development, others have shown no effects. In this study, we have assessed the immunomodulating effects of two probiotic strains, Lactobacillus rhamnosus (L. rhamnosus and Bifidobacterium breve (B. breve on T cell polarization in vitro, using human peripheral blood mononuclear cells (PBMC, and in vivo, using murine dextran sodium sulfate (DSS colitis model. With respect to the latter, the mRNA expression of T cell subset-associated transcription factors and cytokines in the colon was measured and the T helper type (Th 17 and regulatory T cell (Treg subsets were determined in the Peyer's patches. Both L. rhamnosus and B. breve incubations in vitro reduced Th17 and increased Th2 cell subsets in human PBMCs. In addition, B. breve incubation was also able to reduce Th1 and increase Treg cell subsets in contrast to L. rhamnosus. In vivo intervention with B. breve, but not L. rhamnosus, significantly attenuated the severity of DSS-induced colitis. In DSS-treated C57BL/6 mice, intervention with B. breve increased the expression of mRNA encoding for Th2- and Treg-associated cytokines in the distal colon. In addition, intervention with B. breve led to increases of Treg and decreases of Th17 cell subsets in Peyer's patches of DSS-treated mice. B. breve modulates T cell polarization towards Th2 and Treg cell-associated responses in vitro and in vivo. In vivo B. breve intervention ameliorates DSS-induced colitis symptoms and this protective effect may mediated by its effects on the T-cell composition.

  8. Micro-RNA 10a Is Increased in Feline T Regulatory Cells and Increases Foxp3 Protein Expression Following In Vitro Transfection

    Directory of Open Access Journals (Sweden)

    Yan Wang

    2017-02-01

    Full Text Available CD4+CD25+Foxp3+ T regulatory (Treg cells are activated during the course of lentiviral infection and exhibit heightened suppressor function when compared to Treg cells from uninfected controls. Foxp3 is essential to Treg cell function and multiple studies have documented that lentivirus-activated Treg cells exhibit heightened Foxp3 expression when compared to Treg cells from uninfected controls. Our hypothesis was that lentivirus-induced micro-RNAs (miRNAs contribute to heightened Treg cell suppressor function by stabilizing Foxp3 expression. We demonstrated that CD4+CD25+ T cells from both feline immunodeficiency virus infected (FIV+ cats and uninfected control cats exhibit increased miRNA 10a and 21 levels compared to autologous CD4+CD25− T cells but there was no difference in the levels of these miRNAs when Treg cells from FIV+ cats were compared to Treg cells from uninfected controls. Further, there was no increase in Foxp3 mRNA following transfection of miRNA 10a or 21 into a feline cell line. However, transfection with miRNA 10a resulted in increased Foxp3 protein expression.

  9. Software Defined Networking for Improved Wireless Sensor Network Management: A Survey.

    Science.gov (United States)

    Ndiaye, Musa; Hancke, Gerhard P; Abu-Mahfouz, Adnan M

    2017-05-04

    Wireless sensor networks (WSNs) are becoming increasingly popular with the advent of the Internet of things (IoT). Various real-world applications of WSNs such as in smart grids, smart farming and smart health would require a potential deployment of thousands or maybe hundreds of thousands of sensor nodes/actuators. To ensure proper working order and network efficiency of such a network of sensor nodes, an effective WSN management system has to be integrated. However, the inherent challenges of WSNs such as sensor/actuator heterogeneity, application dependency and resource constraints have led to challenges in implementing effective traditional WSN management. This difficulty in management increases as the WSN becomes larger. Software Defined Networking (SDN) provides a promising solution in flexible management WSNs by allowing the separation of the control logic from the sensor nodes/actuators. The advantage with this SDN-based management in WSNs is that it enables centralized control of the entire WSN making it simpler to deploy network-wide management protocols and applications on demand. This paper highlights some of the recent work on traditional WSN management in brief and reviews SDN-based management techniques for WSNs in greater detail while drawing attention to the advantages that SDN brings to traditional WSN management. This paper also investigates open research challenges in coming up with mechanisms for flexible and easier SDN-based WSN configuration and management.

  10. Software Defined Networking for Improved Wireless Sensor Network Management: A Survey

    Directory of Open Access Journals (Sweden)

    Musa Ndiaye

    2017-05-01

    Full Text Available Wireless sensor networks (WSNs are becoming increasingly popular with the advent of the Internet of things (IoT. Various real-world applications of WSNs such as in smart grids, smart farming and smart health would require a potential deployment of thousands or maybe hundreds of thousands of sensor nodes/actuators. To ensure proper working order and network efficiency of such a network of sensor nodes, an effective WSN management system has to be integrated. However, the inherent challenges of WSNs such as sensor/actuator heterogeneity, application dependency and resource constraints have led to challenges in implementing effective traditional WSN management. This difficulty in management increases as the WSN becomes larger. Software Defined Networking (SDN provides a promising solution in flexible management WSNs by allowing the separation of the control logic from the sensor nodes/actuators. The advantage with this SDN-based management in WSNs is that it enables centralized control of the entire WSN making it simpler to deploy network-wide management protocols and applications on demand. This paper highlights some of the recent work on traditional WSN management in brief and reviews SDN-based management techniques for WSNs in greater detail while drawing attention to the advantages that SDN brings to traditional WSN management. This paper also investigates open research challenges in coming up with mechanisms for flexible and easier SDN-based WSN configuration and management.

  11. Antenatal betamethasone attenuates the angiotensin-(1-7)-Mas receptor-nitric oxide axis in isolated proximal tubule cells.

    Science.gov (United States)

    Su, Yixin; Bi, Jianli; Pulgar, Victor M; Chappell, Mark C; Rose, James C

    2017-06-01

    We previously reported a sex-specific effect of antenatal treatment with betamethasone (Beta) on sodium (Na + ) excretion in adult sheep whereby treated males but not females had an attenuated natriuretic response to angiotensin-(1-7) [Ang-(1-7)]. The present study determined the Na + uptake and nitric oxide (NO) response to low-dose Ang-(1-7) (1 pM) in renal proximal tubule cells (RPTC) from adult male and female sheep antenatally exposed to Beta or vehicle. Data were expressed as percentage of basal uptake or area under the curve for Na + or percentage of control for NO. Male Beta RPTC exhibited greater Na + uptake than male vehicle cells (433 ± 28 vs. 330 ± 26%; P 0.05). Ang-(1-7) significantly inhibited Na + uptake in RPTC from vehicle male (214 ± 11%) and from both vehicle (190 ± 14%) and Beta (209 ± 11%) females but failed to attenuate Na + uptake in Beta male cells. Beta exposure also abolished stimulation of NO by Ang-(1-7) in male but not female RPTC. Both the Na + and NO responses to Ang-(1-7) were blocked by Mas receptor antagonist d-Ala 7 -Ang-(1-7). We conclude that the tubular Ang-(1-7)-Mas-NO pathway is attenuated in males and not females by antenatal Beta exposure. Moreover, since primary cultures of RPTC retain both the sex and Beta-induced phenotype of the adult kidney in vivo they appear to be an appropriate cell model to examine the effects of fetal programming on Na + handling by the renal tubules. Copyright © 2017 the American Physiological Society.

  12. Human mesenchymal stromal cells transiently increase cytokine production by activated T cells before suppressing T-cell proliferation: effect of interferon-γ and tumor necrosis factor-α stimulation.

    Science.gov (United States)

    Cuerquis, Jessica; Romieu-Mourez, Raphaëlle; François, Moïra; Routy, Jean-Pierre; Young, Yoon Kow; Zhao, Jing; Eliopoulos, Nicoletta

    2014-02-01

    Mesenchymal stromal cells (MSCs) suppress T-cell proliferation, especially after activation with inflammatory cytokines. We compared the dynamic action of unprimed and interferon (IFN)-γ plus tumor necrosis factor (TNF)-α-pretreated human bone marrow-derived MSCs on resting or activated T cells. MSCs were co-cultured with allogeneic peripheral blood mononuclear cells (PBMCs) at high MSC-to-PBMC ratios in the absence or presence of concomitant CD3/CD28-induced T-cell activation. The kinetic effects of MSCs on cytokine production and T-cell proliferation, cell cycle and apoptosis were assessed. Unprimed MSCs increased the early production of IFN-γ and interleukin (IL)-2 by CD3/CD28-activated PBMCs before suppressing T-cell proliferation. In non-activated PBMC co-cultures, low levels of IL-2 and IL-10 synthesis were observed with MSCs in addition to low levels of CD69 expression by T cells and no T-cell proliferation. MSCs also decreased apoptosis in resting and activated T cells and inhibited the transition of these cells into the sub-G0/G1 and the S phases. With inhibition of indoleamine 2,3 dioxygenase, MSCs increased CD3/CD28-induced T-cell proliferation. After priming with IFN-γ plus TNF-α, MSCs were less potent at increasing cytokine production by CD3/CD28-activated PBMCs and more effective at inhibiting T-cell proliferation but had preserved anti-apoptotic functions. Unprimed MSCs induce a transient increase in IFN-γ and IL-2 synthesis by activated T cells. Pre-treatment of MSCs with IFN-γ plus TNF-α may increase their effectiveness and safety in vivo. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  13. Relation between the Macroscopic Pattern of Elephant Ivory and Its Three-Dimensional Micro-Tubular Network

    Science.gov (United States)

    Albéric, Marie; Dean, Mason N.; Gourrier, Aurélien; Wagermaier, Wolfgang; Dunlop, John W. C.; Staude, Andreas; Fratzl, Peter; Reiche, Ina

    2017-01-01

    Macroscopic, periodic, dark and bright patterns are observed on sections of elephant tusk, in the dentin part (ivory). The motifs—also called Schreger pattern—vary depending on the orientation in the tusk: on sections perpendicular to the tusk axis, a checkerboard pattern is present whereas on sections longitudinal to it, alternating stripes are observed. This pattern has been used to identify elephant and mammoth ivory in archeological artifacts and informs on the continuous tissue growth mechanisms of tusk. However, its origin, assumed to be related to the 3D structure of empty microtubules surrounded by the ivory matrix has yet to be characterized unequivocally. Based on 2D observations of the ivory microtubules by means of a variety of imaging techniques of three different planes (transverse, longitudinal and tangential to the tusk axis), we show that the dark areas of the macroscopic pattern are due to tubules oblique to the surface whereas bright areas are related to tubules parallel to it. The different microstructures observed in the three planes as well as the 3D data obtained by SR-μCT analysis allow us to propose a 3D model of the microtubule network with helical tubules phase-shifted in the tangential direction. The phase shift is a combination of a continuous phase shift of π every 1 mm with a stepwise phase shift of π/2 every 500 μm. By using 3D modeling, we show how the 3D helical model better represents the experimental microstructure observed in 2D planes compared to previous models in the literature. This brings new information on the origin of the unique Schreger pattern of elephant ivory, crucial for better understanding how archaeological objects were processed and for opening new routes to rethink how biological materials are built. PMID:28125603

  14. Carrier ethernet network control plane based on the Next Generation Network

    DEFF Research Database (Denmark)

    Fu, Rong; Wang, Yanmeng; Berger, Michael Stubert

    2008-01-01

    This paper contributes on presenting a step towards the realization of Carrier Ethernet control plane based on the next generation network (NGN). Specifically, transport MPLS (T-MPLS) is taken as the transport technology in Carrier Ethernet. It begins with providing an overview of the evolving...... architecture of the next generation network (NGN). As an essential candidate among the NGN transport technologies, the definition of Carrier Ethernet (CE) is also introduced here. The second part of this paper depicts the contribution on the T-MPLS based Carrier Ethernet network with control plane based on NGN...... at illustrating the improvement of the Carrier Ethernet network with the NGN control plane....

  15. Chronic exposure to trichloroethylene increases DNA methylation of the Ifng promoter in CD4+ T cells.

    Science.gov (United States)

    Gilbert, Kathleen M; Blossom, Sarah J; Erickson, Stephen W; Broadfoot, Brannon; West, Kirk; Bai, Shasha; Li, Jingyun; Cooney, Craig A

    2016-10-17

    CD4 + T cells in female MRL+/+ mice exposed to solvent and water pollutant trichloroethylene (TCE) skew toward effector/memory CD4 + T cells, and demonstrate seemingly non-monotonic alterations in IFN-γ production. In the current study we examined the mechanism for this immunotoxicity using effector/memory and naïve CD4 + T cells isolated every 6 weeks during a 40 week exposure to TCE (0.5mg/ml in drinking water). A time-dependent effect of TCE exposure on both Ifng gene expression and IFN-γ protein production was observed in effector/memory CD4 + T cells, with an increase after 22 weeks of exposure and a decrease after 40 weeks of exposure. No such effect of TCE was observed in naïve CD4 + T cells. A cumulative increase in DNA methylation in the CpG sites of the promoter of the Ifng gene was observed in effector/memory, but not naïve, CD4 + T cells over time. Also unique to the Ifng promoter was an increase in methylation variance in effector/memory compared to naïve CD4 + T cells. Taken together, the CpG sites of the Ifng promoter in effector/memory CD4 + T cells were especially sensitive to the effects of TCE exposure, which may help explain the regulatory effect of the chemical on this gene. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Increased numbers of preexisting memory CD8 T cells and decreased T-bet expression can restrain terminal differentiation of secondary effector and memory CD8 T cells.

    Science.gov (United States)

    Joshi, Nikhil S; Cui, Weiguo; Dominguez, Claudia X; Chen, Jonathan H; Hand, Timothy W; Kaech, Susan M

    2011-10-15

    Memory CD8 T cells acquire effector memory cell properties after reinfection and may reach terminally differentiated, senescent states ("Hayflick limit") after multiple infections. The signals controlling this process are not well understood, but we found that the degree of secondary effector and memory CD8 T cell differentiation was intimately linked to the amount of T-bet expressed upon reactivation and preexisting memory CD8 T cell number (i.e., primary memory CD8 T cell precursor frequency) present during secondary infection. Compared with naive cells, memory CD8 T cells were predisposed toward terminal effector (TE) cell differentiation because they could immediately respond to IL-12 and induce T-bet, even in the absence of Ag. TE cell formation after secondary (2°) or tertiary infections was dependent on increased T-bet expression because T-bet(+/-) cells were resistant to these phenotypic changes. Larger numbers of preexisting memory CD8 T cells limited the duration of 2° infection and the amount of IL-12 produced, and consequently, this reduced T-bet expression and the proportion of 2° TE CD8 T cells that formed. Together, these data show that over repeated infections, memory CD8 T cell quality and proliferative fitness is not strictly determined by the number of serial encounters with Ag or cell divisions, but is a function of the CD8 T cell differentiation state, which is genetically controlled in a T-bet-dependent manner. This differentiation state can be modulated by preexisting memory CD8 T cell number and the intensity of inflammation during reinfection. These results have important implications for vaccinations involving prime-boost strategies.

  17. Effects of advanced glycation end products on ezrin-dependent functions in LLC-PK1 proximal tubule cells.

    Science.gov (United States)

    Bach, Leon A; Gallicchio, Marisa A; McRobert, E Anne; Tikoo, Anjali; Cooper, Mark E

    2005-06-01

    We have recently shown that advanced glycation products (AGEs) bind to the ERM (ezrin, radixin, moesin) family of proteins. ERM proteins act as cross-linkers between cell membrane proteins and the actin cytoskeleton. They are also involved in signal transduction pathways. They therefore have a critical role in normal cell processes, including modulation of cell shape, adhesion, and motility. We postulate that AGEs may contribute to diabetic complications by disrupting ERM function. In support of this hypothesis, AGEs inhibit ezrin-dependent tubulogenesis of proximal tubule cells. Phosphorylation is an important activating mechanism for ERM proteins, and AGEs inhibit ezrin phosphorylation mediated by the epidermal growth factor receptor.

  18. The effect of increasing levels of embedded generation on the distribution network. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Collinson, A; Earp, G K; Howson, D; Owen, R D; Wright, A J

    1999-10-01

    This report was commissioned as part of the EA Technology Strategic Technology Programme under guidance of the Module 5 (Embedded Generation) Steering Group. This report aims to provide information related to the distribution and supply of electricity in the context of increasing levels of embedded generation. There is a brief description of the operating environment within which electricity companies in the UK must operate. Technical issues related to the connection of generation to the existing distribution infrastructure are highlighted and the design philosophy adopted by network designers in accommodating applications for the connection of embedded generation to the network is discussed. The effects embedded generation has on the network and the issues raised are presented as many of them present barriers to the connection of embedded generators. The final chapters cover the forecast of required connection to 2010 and solutions to restrictions preventing the connection of more embedded generation to the network. (author)

  19. Effects of mercury on lysosomal protein digestion in the kidney proximal tubule

    International Nuclear Information System (INIS)

    Madsen, K.M.; Christensen, E.I.

    1978-01-01

    The effect of mercury on renal lysosomal protein digestion was studied after administration of mercury in vitro and in vivo. Mercuric chloride or methylmercury chloride was added in vitro to lysosomal enzymes isolated from normal rats, and subsequently, digestion experiments were carried out using 125 I-labeled lysozyme or cytochrome c as substrate proteins. Both mercury compounds produced a concentration-dependent inhibition of the degradation of the proteins, mercuric chloride being the strongest inhibitor. Mercuric chloride was also administered to rats in vivo for 5 to 8 months. Renal lysosomal enzymes from these animals also had a decreased ability to digest the two substrate proteins. Furthermore, the digestion of lysozyme intravenously injected into mercury-intoxicated rats was decreased in renal cortical slices incubated in vitro. Electron microscope autoradiography showed that intravenously injected labeled lysozyme was located primarily over lysosomes in proximal tubule cells 1 hour after injection in both control animals and mercury-intoxicated rats. These results suggest a decreased catabolism of low molecular weight proteins in the kidney during chronic mercury intoxication

  20. Total glucosides of paeony induces regulatory CD4(+)CD25(+) T cells by increasing Foxp3 demethylation in lupus CD4(+) T cells.

    Science.gov (United States)

    Zhao, Ming; Liang, Gong-ping; Tang, Mei-ni; Luo, Shuang-yan; Zhang, Jing; Cheng, Wen-jing; Chan, Tak-mao; Lu, Qian-jin

    2012-05-01

    Total glucosides of paeony (TGP), an active compound extracted from Paeony root, has been used in therapy for autoimmune diseases. However the molecular mechanism of TGP in the prevention of autoimmune response remains unclear. In this study, we found that TGP treatment significantly increased the percentage and number of Treg cells in lupus CD4(+) T cells. Further investigation revealed that treatment with TGP increased the expression of Foxp3 in lupus CD4(+) T cells by down-regulating Foxp3 promoter methylation levels. However, we couldn't observe similar results in healthy control CD4(+) T cells treated by TGP. Moreover, our results also showed that IFN-γ and IL-2 expression was enhanced in TGP-treated lupus CD4(+) T cells. These findings indicate that TGP inhibits autoimmunity in SLE patients possibly by inducing Treg cell differentiation, which may in turn be due to its ability to regulate the methylation status of the Foxp3 promoter and activate IFN-γ and IL-2 signaling. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Social networking policies in nursing education.

    Science.gov (United States)

    Frazier, Blake; Culley, Joan M; Hein, Laura C; Williams, Amber; Tavakoli, Abbas S

    2014-03-01

    Social networking use has increased exponentially in the past few years. A literature review related to social networking and nursing revealed a research gap between nursing practice and education. Although there was information available on the appropriate use of social networking sites, there was limited research on the use of social networking policies within nursing education. The purpose of this study was to identify current use of social media by faculty and students and a need for policies within nursing education at one institution. A survey was developed and administered to nursing students (n = 273) and nursing faculty (n = 33). Inferential statistics included χ², Fisher exact test, t test, and General Linear Model. Cronbach's α was used to assess internal consistency of social media scales. The χ² result indicates that there were associations with the group and several social media items. t Test results indicate significant differences between student and faculty for average of policies are good (P = .0127), policies and discipline (P = .0315), and policy at the study school (P = .0013). General Linear Model analyses revealed significant differences for "friend" a patient with a bond, unprofessional posts, policy, and nursing with class level. Results showed that students and faculty supported the development of a social networking policy.

  2. A Lactobacillus rhamnosus strain induces a heme oxygenase dependent increase in Foxp3+ regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Khalil Karimi

    Full Text Available We investigated the consequences of feeding with a Lactobacillus species on the immune environment in GALT, and the role of dendritic cells and heme oxygenase-1 in mediating these responses. Feeding with a specific strain of Lactobacillus rhamnosus induced a significant increase in CD4+CD25+Foxp3+ functional regulatory T cells in GALT. This increase was greatest in the mesenteric lymph nodes and associated with a marked decrease in TNF and IFNγ production. Dendritic cell regulatory function and HO-1 expression was also increased. The increase in Foxp3+ T cells could be prevented by treatment with a heme oxygenase inhibitor. However, neither inhibition of heme oxygenase nor blockade of IL-10 and TGFβ prevented the inhibition of inflammatory cytokine production. In conclusion Lactobacillus feeding induced a tolerogenic environment in GALT. HO-1 was critical to the enhancement of Foxp3+ regulatory T cells while additional, as yet unknown, pathways were involved in the down-regulation of inflammatory cytokine production by T cells.

  3. Characteristics of genomic signatures derived using univariate methods and mechanistically anchored functional descriptors for predicting drug- and xenobiotic-induced nephrotoxicity.

    Science.gov (United States)

    Shi, Weiwei; Bugrim, Andrej; Nikolsky, Yuri; Nikolskya, Tatiana; Brennan, Richard J

    2008-01-01

    ABSTRACT The ideal toxicity biomarker is composed of the properties of prediction (is detected prior to traditional pathological signs of injury), accuracy (high sensitivity and specificity), and mechanistic relationships to the endpoint measured (biological relevance). Gene expression-based toxicity biomarkers ("signatures") have shown good predictive power and accuracy, but are difficult to interpret biologically. We have compared different statistical methods of feature selection with knowledge-based approaches, using GeneGo's database of canonical pathway maps, to generate gene sets for the classification of renal tubule toxicity. The gene set selection algorithms include four univariate analyses: t-statistics, fold-change, B-statistics, and RankProd, and their combination and overlap for the identification of differentially expressed probes. Enrichment analysis following the results of the four univariate analyses, Hotelling T-square test, and, finally out-of-bag selection, a variant of cross-validation, were used to identify canonical pathway maps-sets of genes coordinately involved in key biological processes-with classification power. Differentially expressed genes identified by the different statistical univariate analyses all generated reasonably performing classifiers of tubule toxicity. Maps identified by enrichment analysis or Hotelling T-square had lower classification power, but highlighted perturbed lipid homeostasis as a common discriminator of nephrotoxic treatments. The out-of-bag method yielded the best functionally integrated classifier. The map "ephrins signaling" performed comparably to a classifier derived using sparse linear programming, a machine learning algorithm, and represents a signaling network specifically involved in renal tubule development and integrity. Such functional descriptors of toxicity promise to better integrate predictive toxicogenomics with mechanistic analysis, facilitating the interpretation and risk assessment of

  4. Inflammatory mediator bradykinin increases population of sensory neurons expressing functional T-type Ca(2+) channels.

    Science.gov (United States)

    Huang, Dongyang; Liang, Ce; Zhang, Fan; Men, Hongchao; Du, Xiaona; Gamper, Nikita; Zhang, Hailin

    2016-04-29

    T-type Ca(2+) channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca(2+) currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca(2+) channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca(2+) currents while having no effect on the peak LVA current amplitude. When applied individually, BK and ATP also increased the population size of LVA-positive neurons while NE and PGE2 had no effect. The PLC inhibitor U-73122 and B2 receptor antagonist, Hoe-140, both abolished the increase of the population of LVA-positive DRG neurons. Inflammatory treatment did not affect CaV3.2 mRNA or protein levels in DRG cultures. Furthermore, an ubiquitination inhibitor, MG132, did not increase the population of LVA-positive neurons. Our data suggest that inflammatory mediators BK and ATP increase the abundance of LVA-positive DRG neurons in total neuronal population by stimulating the recruitment of a 'reserve pool' of CaV3.2 channels, particularly in neurons that do not display measurable LVA currents under control conditions. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. High epitope expression levels increase competition between T cells.

    Directory of Open Access Journals (Sweden)

    Almut Scherer

    2006-08-01

    Full Text Available Both theoretical predictions and experimental findings suggest that T cell populations can compete with each other. There is some debate on whether T cells compete for aspecific stimuli, such as access to the surface on antigen-presenting cells (APCs or for specific stimuli, such as their cognate epitope ligand. We have developed an individual-based computer simulation model to study T cell competition. Our model shows that the expression level of foreign epitopes per APC determines whether T cell competition is mainly for specific or aspecific stimuli. Under low epitope expression, competition is mainly for the specific epitope stimuli, and, hence, different epitope-specific T cell populations coexist readily. However, if epitope expression levels are high, aspecific competition becomes more important. Such between-specificity competition can lead to competitive exclusion between different epitope-specific T cell populations. Our model allows us to delineate the circumstances that facilitate coexistence of T cells of different epitope specificity. Understanding mechanisms of T cell coexistence has important practical implications for immune therapies that require a broad immune response.

  6. Matrix Completion Optimization for Localization in Wireless Sensor Networks for Intelligent IoT

    Directory of Open Access Journals (Sweden)

    Thu L. N. Nguyen

    2016-05-01

    Full Text Available Localization in wireless sensor networks (WSNs is one of the primary functions of the intelligent Internet of Things (IoT that offers automatically discoverable services, while the localization accuracy is a key issue to evaluate the quality of those services. In this paper, we develop a framework to solve the Euclidean distance matrix completion problem, which is an important technical problem for distance-based localization in WSNs. The sensor network localization problem is described as a low-rank dimensional Euclidean distance completion problem with known nodes. The task is to find the sensor locations through recovery of missing entries of a squared distance matrix when the dimension of the data is small compared to the number of data points. We solve a relaxation optimization problem using a modification of Newton’s method, where the cost function depends on the squared distance matrix. The solution obtained in our scheme achieves a lower complexity and can perform better if we use it as an initial guess for an interactive local search of other higher precision localization scheme. Simulation results show the effectiveness of our approach.

  7. Roles of CD34+ cells and ALK5 signaling in the reconstruction of seminiferous tubule-like structures in 3-D re-aggregate culture of dissociated cells from neonatal mouse testes.

    Science.gov (United States)

    Abe, Shin-Ichi; Abe, Kazuko; Zhang, Jidong; Harada, Tomoaki; Mizumoto, Go; Oshikawa, Hiroki; Akiyama, Haruhiko; Shimamura, Kenji

    2017-01-01

    Tissue reconstruction in vitro can provide, if successful, a refined and simple system to analyze the underlying mechanisms that drive the morphogenesis and maintain the ordered structure. We have recently succeeded in reconstruction of seminiferous cord-like and tubule-like structures using 3-D re-aggregate culture of dissociated testicular cells. In testis formation, endothelial cells that migrated from mesonephroi to embryonic gonads have been shown to be critical for development of testis cords, but how endothelial cells contribute to testis cord formation remains unknown. To decipher the roles of endothelial and peritubular cells in the reconstruction of cord-like and tubule-like structures, we investigated the behavior of CD34+ endothelial and p75+ cells, and peritubular myoid cells (PTMCs) in 3-D re-aggregate cultures of testicular cells. The results showed that these 3 types of cells had the capacity of re-aggregation on their own and with each other, and of segregation into 3 layers in a re-aggregate, which were very similar to interstitial and peritubular tissues in vivo. Observation of behaviors of fluorescent Sertoli cells and other non-fluorescent types of cells using testes from Sox9-EGFP transgenic mice showed dynamic cell movement and segregation in re-aggregate cultures. Cultures of testicular cells deprived of interstitial and peritubular cells resulted in dysmorphic structures, but re-addition of them restored tubule-like structures. Purified CD34+ cells in culture differentiated into p75+ cells and PTMCs. These results indicate that CD34+ cells differentiate into p75+ cells, which then differentiate into PTMCs. TGFβ signaling inhibitors, SB431542 and ALK5i, disturbed the reconstruction of cord-like and tubule-like structures, and the latter compromised re-construction of interstitial-like and peritubular-like structures, as well as the proliferation of CD34+, p75+, PTMCs, and Sertoli cells, and their movement and differentiation. These results

  8. Potassium-transporting proteins in skeletal muscle: cellular location and fiber-type differences

    DEFF Research Database (Denmark)

    Kristensen, Michael; Juel, Carsten

    2010-01-01

    Potassium (K+) displacement in skeletal muscle may be an important factor in the development of muscle fatigue during intense exercise. It has been shown in vitro that an increase in the extracellular K+ concentration ([K+]e) to values higher than approx. 10 mm significantly reduce force developm......Potassium (K+) displacement in skeletal muscle may be an important factor in the development of muscle fatigue during intense exercise. It has been shown in vitro that an increase in the extracellular K+ concentration ([K+]e) to values higher than approx. 10 mm significantly reduce force......, but is suggested primarily to participate in K+ release to the interstitium. Because there is restricted diffusion of K+ to the interstitium, K+ released to the T-tubules during AP propagation will be removed primarily by reuptake mediated by transport proteins located in the T-tubule membrane. The most important...

  9. Externally induced frontoparietal synchronization modulates network dynamics and enhances working memory performance.

    Science.gov (United States)

    Violante, Ines R; Li, Lucia M; Carmichael, David W; Lorenz, Romy; Leech, Robert; Hampshire, Adam; Rothwell, John C; Sharp, David J

    2017-03-14

    Cognitive functions such as working memory (WM) are emergent properties of large-scale network interactions. Synchronisation of oscillatory activity might contribute to WM by enabling the coordination of long-range processes. However, causal evidence for the way oscillatory activity shapes network dynamics and behavior in humans is limited. Here we applied transcranial alternating current stimulation (tACS) to exogenously modulate oscillatory activity in a right frontoparietal network that supports WM. Externally induced synchronization improved performance when cognitive demands were high. Simultaneously collected fMRI data reveals tACS effects dependent on the relative phase of the stimulation and the internal cognitive processing state. Specifically, synchronous tACS during the verbal WM task increased parietal activity, which correlated with behavioral performance. Furthermore, functional connectivity results indicate that the relative phase of frontoparietal stimulation influences information flow within the WM network. Overall, our findings demonstrate a link between behavioral performance in a demanding WM task and large-scale brain synchronization.

  10. Adaptable System Increasing the Transmission Speed and Reliability in Packet Network by Optimizing Delay

    Directory of Open Access Journals (Sweden)

    Zbynek Kocur

    2014-01-01

    Full Text Available There is a great diversity in the transmission technologies in current data networks. Individual technologies are in most cases incompatible at physical and partially also at the link layer of the reference ISO/OSI model. Network compatibility, as the ability to transmit data, is realizable through the third layer, which is able to guarantee the operation of the different devices across their technological differences. The proposed inverse packet multiplexer addresses increase of the speed and reliability of packet transmission to the third layer, and at the same time it increases the stability of the data communication by the regulation of the delay value during the transmission. This article presents implementation of a communication system and its verification in real conditions. The conclusion compares the strengths and weaknesses of the proposed control system.

  11. T-SDN architecture for space and ground integrated optical transport network

    Science.gov (United States)

    Nie, Kunkun; Hu, Wenjing; Gao, Shenghua; Chang, Chengwu

    2015-11-01

    Integrated optical transport network is the development trend of the future space information backbone network. The space and ground integrated optical transport network(SGIOTN) may contain a variety of equipment and systems. Changing the network or meeting some innovation missions in the network will be an expensive implement. Software Defined Network(SDN) provides a good solution to flexibly adding process logic, timely control states and resources of the whole network, as well as shielding the differences of heterogeneous equipment and so on. According to the characteristics of SGIOTN, we propose an transport SDN architecture for it, with hierarchical control plane and data plane composed of packet networks and optical transport networks.

  12. Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study.

    Directory of Open Access Journals (Sweden)

    Makii Muthalib

    Full Text Available Neuroimaging studies have shown neuromuscular electrical stimulation (NMES-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC, premotor cortex (PMC, supplementary motor area (SMA, and secondary somatosensory area (S2, as well as regions of the prefrontal cortex (PFC known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI, and with reference to voluntary (VOL wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb and deoxygenated (HHb hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2. However, the level and area of contralateral sensorimotor network (including PFC activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

  13. Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study.

    Science.gov (United States)

    Muthalib, Makii; Re, Rebecca; Zucchelli, Lucia; Perrey, Stephane; Contini, Davide; Caffini, Matteo; Spinelli, Lorenzo; Kerr, Graham; Quaresima, Valentina; Ferrari, Marco; Torricelli, Alessandro

    2015-01-01

    Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

  14. Endogenous Tim-1 (Kim-1) promotes T-cell responses and cell-mediated injury in experimental crescentic glomerulonephritis.

    Science.gov (United States)

    Nozaki, Yuji; Nikolic-Paterson, David J; Snelgrove, Sarah L; Akiba, Hisaya; Yagita, Hideo; Holdsworth, Stephen R; Kitching, A Richard

    2012-05-01

    The T-cell immunoglobulin mucin 1 (Tim-1) modulates CD4(+) T-cell responses and is also expressed by damaged proximal tubules in the kidney where it is known as kidney injury molecule-1 (Kim-1). We sought to define the role of endogenous Tim-1 in experimental T-cell-mediated glomerulonephritis induced by sheep anti-mouse glomerular basement membrane globulin acting as a planted foreign antigen. Tim-1 is expressed by infiltrating activated CD4(+) cells in this model, and we studied the effects of an inhibitory anti-Tim-1 antibody (RMT1-10) on immune responses and glomerular disease. Crescentic glomerulonephritis, proliferative injury, and leukocyte accumulation were attenuated following treatment with anti-Tim-1 antibodies, but interstitial foxp3(+) cell accumulation and interleukin-10 mRNA were increased. T-cell proliferation and apoptosis decreased in the immune system along with a selective reduction in Th1 and Th17 cellular responses both in the immune system and within the kidney. The urinary excretion and renal expression of Kim-1 was reduced by anti-Tim-1 antibodies reflecting diminished interstitial injury. The effects of anti-Tim-1 antibodies were not apparent in the early phase of renal injury, when the immune response to sheep globulin was developing. Thus, endogenous Tim-1 promotes Th1 and Th17 nephritogenic immune responses and its neutralization reduces renal injury while limiting inflammation in cell-mediated glomerulonephritis.

  15. Increased memory phenotypes of CD4+ and CD8+ T cells in ...

    African Journals Online (AJOL)

    Conclusions: Children with SCA in Tanzania show an absolute increase in all leukocyte types, including lymphocytes, with skewing of both CD4+ and CD8+ T cells towards the memory phenotypes. These findings provide insights on the development of adaptive immunity which may have implications on vaccine ...

  16. Increase of Power System Survivability with the Decision Support Tool CRIPS Based on Network Planning and Simulation Program PSS®SINCAL

    Science.gov (United States)

    Schwaegerl, Christine; Seifert, Olaf; Buschmann, Robert; Dellwing, Hermann; Geretshuber, Stefan; Leick, Claus

    The increased interconnection and automation of critical infrastructures enlarges the complexity of the dependency structures and - as consequence - the danger of cascading effects, e.g. causing area-wide blackouts in power supply networks that are currently after deregulation operated closer to their limits. New tools or an intelligent combination of existing approaches are required to increase the survivability of critical infrastructures. Within the IRRIIS project the expert system CRIPS was developed based on network simulations realised with PSS®SINCAL, an established tool to support the analysis and planning of electrical power, gas, water or heat networks. CRIPS assesses the current situation in power supply networks analysing the simulation results of the physical network behaviour and recommends corresponding decisions.

  17. Time and Energy Efficient Relay Transmission for Multi-Hop Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Jin-Woo Kim

    2016-06-01

    Full Text Available The IEEE 802.15.4 standard is widely recognized as one of the most successful enabling technologies for short range low rate wireless communications and it is used in IoT applications. It covers all the details related to the MAC and PHY layers of the IoT protocol stack. Due to the nature of IoT, the wireless sensor networks are autonomously self-organized networks without infrastructure support. One of the issues in IoT is the network scalability. To address this issue, it is necessary to support the multi-hop topology. The IEEE 802.15.4 network can support a star, peer-to-peer, or cluster-tree topology. One of the IEEE 802.15.4 topologies suited for the high predictability of performance guarantees and energy efficient behavior is a cluster-tree topology where sensor nodes can switch off their transceivers and go into a sleep state to save energy. However, the IEEE 802.15.4 cluster-tree topology may not be able to provide sufficient bandwidth for the increased traffic load and the additional information may not be delivered successfully. The common drawback of the existing approaches is that they do not address the poor bandwidth utilization problem in IEEE 802.15.4 cluster-tree networks, so it is difficult to increase the network performance. Therefore, to solve this problem in this paper we study a relay transmission protocol based on the standard protocol in the IEEE 802.15.4 MAC. In the proposed scheme, the coordinators can relay data frames to their parent devices or their children devices without contention and can provide bandwidth for the increased traffic load or the number of devices. We also evaluate the performance of the proposed scheme through simulation. The simulation results demonstrate that the proposed scheme can improve the reliability, the end-to-end delay, and the energy consumption.

  18. Thyroid hormone-dependent development of early cortical networks: Temporal specificity and the contribution of trkB and mTOR pathways

    Directory of Open Access Journals (Sweden)

    Sören eWesterholz

    2013-08-01

    Full Text Available Early in neocortical network development, triiodothyronine (T3 promotes GABAergic neurons’ population increase, their somatic growth and the formation of GABAergic synapses. In the presence of T3, GABAergic interneurons form longer axons and conspicuous axonal arborizations, with an increased number of putative synaptic boutons. Here we show that the increased GABAergic axonal growth is positively correlated with the proximity to non-GABAergic neurons. A differential innervation emerges from a T3-dependent decrease of axonal length in fields with low density of neuronal cell bodies, combined with an increased bouton formation in fields with high density of neuronal somata. T3 addition to deprived networks after the first two weeks of development did not rescue deficits in the GABAergic synaptic bouton distribution, or in the frequency and duration of spontaneous bursts. During the critical two-week-period, GABAergic signaling is depolarizing as revealed by calcium imaging experiments. Interestingly, T3 enhanced the expression of the potassium-chloride cotransporter 2 (KCC2, and accelerated the developmental shift from depolarizing to hyperpolarizing GABAergic signaling in non-GABAergic neurons.The T3-related increase of spontaneous network activity was remarkably reduced after blockade of either tropomyosin-receptor kinase B (trkB or mammalian target of rapamycin (mTOR pathways. T3-dependent increase in GABAergic neurons’ soma size was mediated mainly by mTOR signaling. Conversely, the T3-dependent selective increase of GABAergic boutons near non-GABAergic cell bodies is mediated by trkB signaling only. Both trkB and mTOR signaling mediate T3-dependent reduction of the GABAergic axon extension. The circuitry context is relevant for the interaction between T3 and trkB signaling, but not for the interactions between T3 and mTOR signaling.

  19. EIGENVECTOR-BASED CENTRALITY MEASURES FOR TEMPORAL NETWORKS*

    Science.gov (United States)

    TAYLOR, DANE; MYERS, SEAN A.; CLAUSET, AARON; PORTER, MASON A.; MUCHA, PETER J.

    2017-01-01

    Numerous centrality measures have been developed to quantify the importances of nodes in time-independent networks, and many of them can be expressed as the leading eigenvector of some matrix. With the increasing availability of network data that changes in time, it is important to extend such eigenvector-based centrality measures to time-dependent networks. In this paper, we introduce a principled generalization of network centrality measures that is valid for any eigenvector-based centrality. We consider a temporal network with N nodes as a sequence of T layers that describe the network during different time windows, and we couple centrality matrices for the layers into a supra-centrality matrix of size NT × NT whose dominant eigenvector gives the centrality of each node i at each time t. We refer to this eigenvector and its components as a joint centrality, as it reflects the importances of both the node i and the time layer t. We also introduce the concepts of marginal and conditional centralities, which facilitate the study of centrality trajectories over time. We find that the strength of coupling between layers is important for determining multiscale properties of centrality, such as localization phenomena and the time scale of centrality changes. In the strong-coupling regime, we derive expressions for time-averaged centralities, which are given by the zeroth-order terms of a singular perturbation expansion. We also study first-order terms to obtain first-order-mover scores, which concisely describe the magnitude of nodes’ centrality changes over time. As examples, we apply our method to three empirical temporal networks: the United States Ph.D. exchange in mathematics, costarring relationships among top-billed actors during the Golden Age of Hollywood, and citations of decisions from the United States Supreme Court. PMID:29046619

  20. Zero percolation threshold in electric conductivity of aluminum nanowire network fabricated by chemical etching using an electrospun nanofiber mask

    Science.gov (United States)

    Azuma, Keisuke; Sakajiri, Koichi; Okabe, Takashi; Matsumoto, Hidetoshi; Kang, Sungmin; Watanabe, Junji; Tokita, Masatoshi

    2017-09-01

    We investigated the sheet resistance (R s) and transmittance (T) of seamless two-dimensional networks of 50-nm-thick aluminum (Al) nanowires (NWs) with widths (W) ranging from 380 to 1410 nm. The Al NWs were fabricated by wet-etching of Al metalized polyester films with using polystyrene (PS) nanofibers as the mask. The PS nanofibers were deposited by the electrospinning of a PS solution and adhered to the film by annealing. W and the area coverage (φ) were increased with increasing PS solution concentration and deposition time, respectively. With increasing φ from 3 to 34%, T and R s decreased from 99 to 75% and from 800 to 10 Ω/sq, respectively, and the network with W = 878 nm at φ = 0.21 attained values of T = 91% and R s = 31 Ω/sq. The conductivity increases with φ with an exponent of 2, demonstrating that seamless NW networks are characterized by the zero percolation threshold.

  1. Neuronal synchrony detection on single-electron neural networks

    International Nuclear Information System (INIS)

    Oya, Takahide; Asai, Tetsuya; Kagaya, Ryo; Hirose, Tetsuya; Amemiya, Yoshihito

    2006-01-01

    Synchrony detection between burst and non-burst spikes is known to be one functional example of depressing synapses. Kanazawa et al. demonstrated synchrony detection with MOS depressing synapse circuits. They found that the performance of a network with depressing synapses that discriminates between burst and random input spikes increases non-monotonically as the static device mismatch is increased. We designed a single-electron depressing synapse and constructed the same network as in Kanazawa's study to develop noise-tolerant single-electron circuits. We examined the temperature characteristics and explored possible architecture that enables single-electron circuits to operate at T > 0 K

  2. Characterization of rPEPT2-mediated Gly-Sar transport parameters in the rat kidney proximal tubule cell line SKPT-0193 cl.2 cultured in basic growth media

    DEFF Research Database (Denmark)

    Bravo, Silvina A; Nielsen, Carsten Uhd; Frokjaer, Sven

    2005-01-01

    The rat proximal kidney tubule cell line SKPT-0193 cl.2 (SKPT) expresses the di-/tripeptide transporter PEPT2 (rPEPT2) and has been used to study PEPT2-mediated transport. Traditionally, SKPT cells have been cultured in growth media supplemented with epidermal growth factor (EGF), apotransferrin,...

  3. Measurement of the t$\\bar{t}$ production cross section in the ET+jets channel at CDF

    Energy Technology Data Exchange (ETDEWEB)

    Compostella, Gabriele [Univ. of Trento (Italy)

    2008-03-06

    This thesis is focused on an inclusive search of the t$\\bar{t}$ → ET + jets decay channel by means of neural network tools in proton antiproton collisions at √s = 1.96 TeV recorded by the Collider Detector at Fermilab (CDF). At the Tevatron p$\\bar{p}$ collider top quarks are mainly produced in pairs through quark-antiquark annihilation and gluon-gluon fusion processes; in the Standard Model description, the top quark then decays to a W boson and a b quark almost 100% of the times, so that its decay signatures are classified according to the W decay modes. When only one W decays leptonically, the t$\\bar{t}$ event typically contains a charged lepton, missing transverse energy due to the presence of a neutrino escaping from the detector, and four high transverse momentum jets, two of which originate from b quarks. In this thesis we describe a t$\\bar{t}$ production cross section measurement which uses data collected by a 'multijet' trigger, and selects this kind of top decays by requiring a high-PT neutrino signature and by using an optimized neural network to discriminate top quark pair production from backgrounds. In Chapter 1, a brief review of the Standard Model of particle physics will be discussed, focusing on top quark properties and experimental signatures. In Chapter 2 will be presented an overview of the Tevatron accelerator chain that provides p$\\bar{p}$ collisions at the center-of-mass energy of √s = 1.96 TeV, and proton and antiproton beams production procedure will be discussed. The CDF detector and its components and subsystems used for the study of p{bar p} collisions provided by the Tevatron will be described in Chapter 3. Chapter 4 will detail the reconstruction procedures used in CDF to detect physical objects exploiting the features of the different detector subsystems. Chapter 5 will provide an overview of the main concepts regarding Artificial Neural Networks, one of the most important tools we will use

  4. Urinary Excretion of Tetrodotoxin Modeled in a Porcine Renal Proximal Tubule Epithelial Cell Line, LLC-PK1

    Directory of Open Access Journals (Sweden)

    Takuya Matsumoto

    2017-07-01

    Full Text Available This study examined the urinary excretion of tetrodotoxin (TTX modeled in a porcine renal proximal tubule epithelial cell line, LLC-PK1. Time course profiles of TTX excretion and reabsorption across the cell monolayers at 37 °C showed that the amount of TTX transported increased linearly for 60 min. However, at 4 °C, the amount of TTX transported was approximately 20% of the value at 37 °C. These results indicate that TTX transport is both a transcellular and carrier-mediated process. Using a transport inhibition assay in which cell monolayers were incubated with 50 µM TTX and 5 mM of a transport inhibitor at 37 °C for 30 min, urinary excretion was significantly reduced by probenecid, tetraethylammonium (TEA, l-carnitine, and cimetidine, slightly reduced by p-aminohippuric acid (PAH, and unaffected by 1-methyl-4-phenylpyridinium (MPP+, oxaliplatin, and cefalexin. Renal reabsorption was significantly reduced by PAH, but was unaffected by probenecid, TEA and l-carnitine. These findings indicate that TTX is primarily excreted by organic cation transporters (OCTs and organic cation/carnitine transporters (OCTNs, partially transported by organic anion transporters (OATs and multidrug resistance-associated proteins (MRPs, and negligibly transported by multidrug and toxic compound extrusion transporters (MATEs.

  5. Intrusion Detection System In IoT

    OpenAIRE

    Nygaard, Frederik

    2017-01-01

    Intrusion detection detects misbehaving nodes in a network. In Internet of Things(IoT), IPv6 Routing for Low-Power and Lossy Networks (RPL) is the standard routing protocol. In IoT, devices commonly have low energy, storage and memory, which is why the implemented intrusion algorithm in this thesis will try to minimize the usage of these resources. IDS for RPL-networks have been implemented before, but the use of resources or the number of packets sent was too high to be successful when findi...

  6. Increased frequencies of IL-31-producing T cells are found in chronic atopic dermatitis skin

    NARCIS (Netherlands)

    Szegedi, Krisztina; Kremer, Andreas E.; Kezic, Sanja; Teunissen, Marcel B. M.; Bos, Jan D.; Luiten, Rosalie M.; Res, Pieter C.; Middelkamp-Hup, Maritza A.

    2012-01-01

    Interleukin (IL)-31 has been associated with pruritus, a characteristic feature of atopic dermatitis (AD). Local T cell responses may be responsible for the increased level of IL-31 mRNA observed in AD. We investigated the frequency of IL-31-producing T cells in AD lesions, as well as their cytokine

  7. Pre-existing malignancy results in increased prevalence of distinct populations of CD4+ T cells during sepsis.

    Science.gov (United States)

    Xie, Jianfeng; Robertson, Jennifer M; Chen, Ching-Wen; Zhang, Wenxiao; Coopersmith, Craig M; Ford, Mandy L

    2018-01-01

    The presence of pre-existing malignancy in murine hosts results in increased immune dysregulation and risk of mortality following a septic insult. Based on the known systemic immunologic changes that occur in cancer hosts, we hypothesized that the presence of pre-existing malignancy would result in phenotypic and functional changes in CD4+ T cell responses following sepsis. In order to conduct a non-biased, unsupervised analysis of phenotypic differences between CD4+ T cell compartments, cohorts of mice were injected with LLC1 tumor cells and tumors were allowed to grow for 3 weeks. These cancer hosts and age-matched non-cancer controls were then subjected to CLP. Splenocytes were harvested at 24h post CLP and flow cytometry and SPADE (Spanning-tree Progression Analysis of Density-normalized Events) were used to analyze populations of CD4+ cells most different between the two groups. Results indicated that relative to non-cancer controls, cancer mice contained more resting memory CD4+ T cells, more activated CD4+ effectors, and fewer naïve CD4+ T cells during sepsis, suggesting that the CD4+ T cell compartment in cancer septic hosts is one of increased activation and differentiation. Moreover, cancer septic animals exhibited expansion of two distinct subsets of CD4+ T cells relative to previously healthy septic controls. Specifically, we identified increases in both a PD-1hi population and a distinct 2B4hi BTLAhi LAG-3hi population in cancer septic animals. By combining phenotypic analysis of exhaustion markers with functional analysis of cytokine production, we found that PD-1+ CD4+ cells in cancer hosts failed to make any cytokines following CLP, while the 2B4+ PD-1lo cells in cancer mice secreted increased TNF during sepsis. In sum, the immunophenotypic landscape of cancer septic animals is characterized by both increased CD4+ T cell activation and exhaustion, findings that may underlie the observed increased mortality in mice with pre-existing malignancy

  8. Pre-existing malignancy results in increased prevalence of distinct populations of CD4+ T cells during sepsis.

    Directory of Open Access Journals (Sweden)

    Jianfeng Xie

    Full Text Available The presence of pre-existing malignancy in murine hosts results in increased immune dysregulation and risk of mortality following a septic insult. Based on the known systemic immunologic changes that occur in cancer hosts, we hypothesized that the presence of pre-existing malignancy would result in phenotypic and functional changes in CD4+ T cell responses following sepsis. In order to conduct a non-biased, unsupervised analysis of phenotypic differences between CD4+ T cell compartments, cohorts of mice were injected with LLC1 tumor cells and tumors were allowed to grow for 3 weeks. These cancer hosts and age-matched non-cancer controls were then subjected to CLP. Splenocytes were harvested at 24h post CLP and flow cytometry and SPADE (Spanning-tree Progression Analysis of Density-normalized Events were used to analyze populations of CD4+ cells most different between the two groups. Results indicated that relative to non-cancer controls, cancer mice contained more resting memory CD4+ T cells, more activated CD4+ effectors, and fewer naïve CD4+ T cells during sepsis, suggesting that the CD4+ T cell compartment in cancer septic hosts is one of increased activation and differentiation. Moreover, cancer septic animals exhibited expansion of two distinct subsets of CD4+ T cells relative to previously healthy septic controls. Specifically, we identified increases in both a PD-1hi population and a distinct 2B4hi BTLAhi LAG-3hi population in cancer septic animals. By combining phenotypic analysis of exhaustion markers with functional analysis of cytokine production, we found that PD-1+ CD4+ cells in cancer hosts failed to make any cytokines following CLP, while the 2B4+ PD-1lo cells in cancer mice secreted increased TNF during sepsis. In sum, the immunophenotypic landscape of cancer septic animals is characterized by both increased CD4+ T cell activation and exhaustion, findings that may underlie the observed increased mortality in mice with pre

  9. Transcranial direct current stimulation (tDCS) for improving capacity in activities and arm function after stroke: a network meta-analysis of randomised controlled trials.

    Science.gov (United States)

    Elsner, Bernhard; Kwakkel, Gert; Kugler, Joachim; Mehrholz, Jan

    2017-09-13

    Transcranial Direct Current Stimulation (tDCS) is an emerging approach for improving capacity in activities of daily living (ADL) and upper limb function after stroke. However, it remains unclear what type of tDCS stimulation is most effective. Our aim was to give an overview of the evidence network regarding the efficacy and safety of tDCS and to estimate the effectiveness of the different stimulation types. We performed a systematic review of randomised trials using network meta-analysis (NMA), searching the following databases until 5 July 2016: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, and four other databases. We included studies with adult people with stroke. We compared any kind of active tDCS (anodal, cathodal, or dual, that is applying anodal and cathodal tDCS concurrently) regarding improvement of our primary outcome of ADL capacity, versus control, after stroke. CRD42016042055. We included 26 studies with 754 participants. Our NMA showed evidence of an effect of cathodal tDCS in improving our primary outcome, that of ADL capacity (standardized mean difference, SMD = 0.42; 95% CI 0.14 to 0.70). tDCS did not improve our secondary outcome, that of arm function, measured by the Fugl-Meyer upper extremity assessment (FM-UE). There was no difference in safety between tDCS and its control interventions, measured by the number of dropouts and adverse events. Comparing different forms of tDCS shows that cathodal tDCS is the most promising treatment option to improve ADL capacity in people with stroke.

  10. Suicide Gene Therapy to Increase the Safety of Chimeric Antigen Receptor-Redirected T Lymphocytes

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    Monica Casucci, Attilio Bondanza

    2011-01-01

    Full Text Available Chimeric antigen receptors (CARs are generated by fusing the antigen-binding motif of a monoclonal antibody (mAb with the signal transduction machinery of the T-cell receptor (TCR. The genetic modification of T lymphocytes with chimeric receptors specific for tumor-associated antigens (TAAs allows for the redirection towards tumor cells. Clinical experience with CAR-redirected T cells suggests that antitumor efficacy associates with some degree of toxicity, especially when TAA expression is shared with healthy tissues. This situation closely resembles the case of allogeneic hematopoietic stem cell transplantation (HSCT, wherein allorecognition causes both the graft-versus-leukemia (GVL effect and graft-versus-host disease (GVHD. Suicide gene therapy, i.e. the genetic induction of a conditional suicide phenotype into donor T cells, enables dissociating the GVL effect from GVHD. Applying suicide gene modification to CAR-redirected T cells may therefore greatly increase their safety profile and facilitate their clinical development.

  11. Cadmium induces Wnt signaling to upregulate proliferation and survival genes in sub-confluent kidney proximal tubule cells

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    Wolff Natascha A

    2010-05-01

    Full Text Available Abstract Background The class 1 carcinogen cadmium (Cd2+ disrupts the E-cadherin/β-catenin complex of epithelial adherens junctions (AJs and causes renal cancer. Deregulation of E-cadherin adhesion and changes in Wnt/β-catenin signaling are known to contribute to carcinogenesis. Results We investigated Wnt signaling after Cd2+-induced E-cadherin disruption in sub-confluent cultured kidney proximal tubule cells (PTC. Cd2+ (25 μM, 3-9 h caused nuclear translocation of β-catenin and triggered a Wnt response measured by TOPflash reporter assays. Cd2+ reduced the interaction of β-catenin with AJ components (E-cadherin, α-catenin and increased binding to the transcription factor TCF4 of the Wnt pathway, which was upregulated and translocated to the nucleus. While Wnt target genes (c-Myc, cyclin D1 and ABCB1 were up-regulated by Cd2+, electromobility shift assays showed increased TCF4 binding to cyclin D1 and ABCB1 promoter sequences with Cd2+. Overexpression of wild-type and mutant TCF4 confirmed Cd2+-induced Wnt signaling. Wnt signaling elicited by Cd2+ was not observed in confluent non-proliferating cells, which showed increased E-cadherin expression. Overexpression of E-cadherin reduced Wnt signaling, PTC proliferation and Cd2+ toxicity. Cd2+ also induced reactive oxygen species dependent expression of the pro-apoptotic ER stress marker and Wnt suppressor CHOP/GADD153 which, however, did not abolish Wnt response and cell viability. Conclusions Cd2+ induces Wnt signaling in PTC. Hence, Cd2+ may facilitate carcinogenesis of PTC by promoting Wnt pathway-mediated proliferation and survival of pre-neoplastic cells.

  12. Network periodic solutions: patterns of phase-shift synchrony

    International Nuclear Information System (INIS)

    Golubitsky, Martin; Wang, Yunjiao; Romano, David

    2012-01-01

    We prove the rigid phase conjecture of Stewart and Parker. It then follows from previous results (of Stewart and Parker and our own) that rigid phase-shifts in periodic solutions on a transitive network are produced by a cyclic symmetry on a quotient network. More precisely, let X(t) = (x 1 (t), ..., x n (t)) be a hyperbolic T-periodic solution of an admissible system on an n-node network. Two nodes c and d are phase-related if there exists a phase-shift θ cd in [0, 1) such that x d (t) = x c (t + θ cd T). The conjecture states that if phase relations persist under all small admissible perturbations (that is, the phase relations are rigid), then for each pair of phase-related cells, their input signals are also phase-related to the same phase-shift. For a transitive network, rigid phase relations can also be described abstractly as a Z m permutation symmetry of a quotient network. We discuss how patterns of phase-shift synchrony lead to rigid synchrony, rigid phase synchrony, and rigid multirhythms, and we show that for each phase pattern there exists an admissible system with a periodic solution with that phase pattern. Finally, we generalize the results to nontransitive networks where we show that the symmetry that generates rigid phase-shifts occurs on an extension of a quotient network

  13. Early gene Broad complex plays a key role in regulating the immune response triggered by ecdysone in the Malpighian tubules of Drosophila melanogaster.

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    Verma, Puja; Tapadia, Madhu G

    2015-08-01

    In insects, humoral response to injury is accomplished by the production of antimicrobial peptides (AMPs) which are secreted in the hemolymph to eliminate the pathogen. Drosophila Malpighian tubules (MTs), however, are unique immune organs that show constitutive expression of AMPs even in unchallenged conditions and the onset of immune response is developmental stage dependent. Earlier reports have shown ecdysone positively regulates immune response after pathogenic challenge however, a robust response requires prior potentiation by the hormone. Here we provide evidence to show that MTs do not require prior potentiation with ecdysone hormone for expression of AMPs and they respond to ecdysone very fast even without immune challenge, although the different AMPs Diptericin, Cecropin, Attacin, Drosocin show differential expression in response to ecdysone. We show that early gene Broad complex (BR-C) could be regulating the IMD pathway by activating Relish and physically interacting with it to activate AMPs expression. BR-C depletion from Malpighian tubules renders the flies susceptible to infection. We also show that in MTs ecdysone signaling is transduced by EcR-B1 and B2. In the absence of ecdysone signaling the IMD pathway associated genes are down regulated and activation and translocation of transcription factor Relish is also affected. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Permeation of macromolecules into the renal glomerular basement membrane and capture by the tubules

    Science.gov (United States)

    Lawrence, Marlon G.; Altenburg, Michael K.; Sanford, Ryan; Willett, Julian D.; Bleasdale, Benjamin; Ballou, Byron; Wilder, Jennifer; Li, Feng; Miner, Jeffrey H.; Berg, Ulla B.; Smithies, Oliver

    2017-01-01

    How the kidney prevents urinary excretion of plasma proteins continues to be debated. Here, using unfixed whole-mount mouse kidneys, we show that fluorescent-tagged proteins and neutral dextrans permeate into the glomerular basement membrane (GBM), in general agreement with Ogston's 1958 equation describing how permeation into gels is related to molecular size. Electron-microscopic analyses of kidneys fixed seconds to hours after injecting gold-tagged albumin, negatively charged gold nanoparticles, and stable oligoclusters of gold nanoparticles show that permeation into the lamina densa of the GBM is size-sensitive. Nanoparticles comparable in size with IgG dimers do not permeate into it. IgG monomer-sized particles permeate to some extent. Albumin-sized particles permeate extensively into the lamina densa. Particles traversing the lamina densa tend to accumulate upstream of the podocyte glycocalyx that spans the slit, but none are observed upstream of the slit diaphragm. At low concentrations, ovalbumin-sized nanoparticles reach the primary filtrate, are captured by proximal tubule cells, and are endocytosed. At higher concentrations, tubular capture is saturated, and they reach the urine. In mouse models of Pierson’s or Alport’s proteinuric syndromes resulting from defects in GBM structural proteins (laminin β2 or collagen α3 IV), the GBM is irregularly swollen, the lamina densa is absent, and permeation is increased. Our observations indicate that size-dependent permeation into the lamina densa of the GBM and the podocyte glycocalyx, together with saturable tubular capture, determines which macromolecules reach the urine without the need to invoke direct size selection by the slit diaphragm. PMID:28246329

  15. Increased native T1-values at the interventricular insertion regions in precapillary pulmonary hypertension.

    Science.gov (United States)

    Spruijt, Onno A; Vissers, Loek; Bogaard, Harm-Jan; Hofman, Mark B M; Vonk-Noordegraaf, Anton; Marcus, J Tim

    2016-03-01

    Cardiac magnetic resonance imaging of the pressure overloaded right ventricle (RV) of precapillary pulmonary hypertension (PH) patients, exhibits late gadolinium enhancement at the interventricular insertion regions, a phenomenon which has been linked to focal fibrosis. Native T1-mapping is an alternative technique to characterize myocardium and has the advantage of not requiring the use of contrast agents. The aim of this study was to characterize the myocardium of idiopathic pulmonary arterial hypertension (IPAH), systemic scleroderma related PH (PAH-Ssc) and chronic thromboembolic PH (CTEPH) patients using native T1-mapping and to see whether native T1-values were related to disease severity. Furthermore, we compared native T1-values between the different precapillary PH categories. Native T1-mapping was performed in 46 IPAH, 14 PAH-SSc and 10 CTEPH patients and 10 control subjects. Native T1-values were assessed using regions of interest at the RV and LV free wall, interventricular septum and interventricular insertion regions. In PH patients, native T1-values of the interventricular insertion regions were significantly higher than the native T1-values of the RV free wall, LV free wall and interventricular septum. Native T1-values at the insertion regions were significantly related to disease severity. Native T1-values were not different between IPAH, PAH-Ssc and CTEPH patients. Native T1-values of the interventricular insertion regions are significantly increased in precapillary PH and are related to disease severity. Native T1-mapping can be developed as an alternative technique for the characterization of the interventricular insertion regions and has the advantage of not requiring the use of contrast agents.

  16. Increased cortical-limbic anatomical network connectivity in major depression revealed by diffusion tensor imaging.

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    Peng Fang

    Full Text Available Magnetic resonance imaging studies have reported significant functional and structural differences between depressed patients and controls. Little attention has been given, however, to the abnormalities in anatomical connectivity in depressed patients. In the present study, we aim to investigate the alterations in connectivity of whole-brain anatomical networks in those suffering from major depression by using machine learning approaches. Brain anatomical networks were extracted from diffusion magnetic resonance images obtained from both 22 first-episode, treatment-naive adults with major depressive disorder and 26 matched healthy controls. Using machine learning approaches, we differentiated depressed patients from healthy controls based on their whole-brain anatomical connectivity patterns and identified the most discriminating features that represent between-group differences. Classification results showed that 91.7% (patients=86.4%, controls=96.2%; permutation test, p<0.0001 of subjects were correctly classified via leave-one-out cross-validation. Moreover, the strengths of all the most discriminating connections were increased in depressed patients relative to the controls, and these connections were primarily located within the cortical-limbic network, especially the frontal-limbic network. These results not only provide initial steps toward the development of neurobiological diagnostic markers for major depressive disorder, but also suggest that abnormal cortical-limbic anatomical networks may contribute to the anatomical basis of emotional dysregulation and cognitive impairments associated with this disease.

  17. IoT-B&B: Edge-Based NFV for IoT Devices with CPE Crowdsourcing

    Directory of Open Access Journals (Sweden)

    He Zhu

    2018-01-01

    Full Text Available For embracing the ubiquitous Internet-of-Things (IoT devices, edge computing and Network Function Virtualization (NFV have been enabled in branch offices and homes in the form of virtual Customer-Premises Equipment (vCPE. A Service Provider (SP deploys vCPE instances as Virtual Network Functions (VNFs on top of generic physical Customer-Premises Equipment (pCPE to ease administration. Upon a usage surge of IoT devices at a certain part of the network, vCPU, memory, and other resource limitations of a single pCPE node make it difficult to add new services handling the high demand. In this paper, we present IoT-B&B, a novel architecture featuring resource sharing of pCPE nodes. When a pCPE node has sharable resources available, the SP will utilize its free resources as a “bed-and-breakfast” place to deploy vCPE instances in need. A placement algorithm is also presented to assign vCPE instances to a cost-efficient pCPE node. By keeping vCPE instances at the network edge, their costs of hosting are reduced. Meanwhile, the transmission latencies are maintained at acceptable levels for processing real-time data burst from IoT devices. The traffic load to the remote, centralized cloud can be substantially reduced.

  18. Stage-specific and age-dependent profiles of zinc, copper, manganese, and selenium in rat seminiferous tubules

    International Nuclear Information System (INIS)

    Homma-Takeda, S.; Nishimura, Y.; Watanabe, Y.; Imaseki, H.; Yukawa, M.

    2004-01-01

    Stage-specific and age-dependent profiles of zinc, copper, manganese, and selenium in testis were examined in Wistar rats by both inductively coupled argon plasma-mass spectrometry (ICP-MS) with a microdissection technique and in situ elemental imaging of micro-PIXE analysis. The young adult animals (10 weeks old) contained higher levels of zinc and manganese in the seminiferous tubules at stages VII-VIII than stages XI through VI and IX-X and the levels were higher than those of the immature and old animals. Copper and selenium levels at stages VII-VIII of the young adult animals were also higher than those of the immature and old animals. In stages VII and VIII, zinc was higher in the central area of the seminiferous epithelium, where spermatozoa were localized, demonstrating a cell-specific property. (author)

  19. Simulation study on effects of signaling network structure on the developmental increase in complexity

    Energy Technology Data Exchange (ETDEWEB)

    Keranen, Soile V.E.

    2003-04-02

    The developmental increase in structural complexity in multicellular life forms depends on local, often non-periodic differences in gene expression. These depend on a network of gene-gene interactions coded within the organismal genome. To better understand how genomic information generates complex expression patterns, I have modeled the pattern forming behavior of small artificial genomes in virtual blastoderm embryos. I varied several basic properties of these genomic signaling networks, such as the number of genes, the distributions of positive (inductive) and negative (repressive) interactions, and the strengths of gene-gene interactions, and analyzed their effects on developmental pattern formation. The results show how even simple genomes can generate complex non-periodic patterns under suitable conditions. They also show how the frequency of complex patterns depended on the numbers and relative arrangements of positive and negative interactions. For example, negative co-regulation of signaling pathway components increased the likelihood of (complex) patterns relative to differential negative regulation of the pathway components. Interestingly, neither quantitative differences either in strengths of signaling interactions nor multiple response thresholds to signal concentration (as in morphogen gradients) were essential for formation of multiple, spatially unique cell types. Thus, with combinatorial code of gene regulation and hierarchical signaling interactions, it is theoretically possible to organize metazoan embryogenesis with just a small fraction of the metazoan genome. Because even small networks can generate complex patterns when they contain a suitable set of connections, evolution of metazoan complexity may have depended more on selection for favourable configurations of signaling interactions than on the increase in numbers of regulatory genes.

  20. Increasing doses effect of L-T4 and L-T3 in the hypothalamus - hypophysis - thyroid in patients carrier of congenital and acquired hypothyroidism

    International Nuclear Information System (INIS)

    Cavaliere, H.

    1987-01-01

    The pituitary and peripheral response to L-T4 and L-T3 therapy were studied in 12 patients with congenital goitrous hypothyroidism, in 10 patients with an ectopic thyroid and onset of hypothyroidism at 3-8 years of age, and in 6 patients with adult-onset hypothyroidism, after they had had their chronic thyroid hormone replacement therapy discontinued for 30 days. They were first treated with increasing L-T4 (0.1, 0.2, and 0.4 mg daily) followed by L-T3 (0.05 and 0.2 mg daily) after stopping thyroid medication for another month. Ten normal subjects were treated identically. Since all patients received similar doses of thyroid hormones (μg/Kg of body weight) and had similar serum levels of T4 and T3 on each dose of L-T4 or L-T3, this paper concludes that congenitally hypothyroid patients have persistent pituitary resistance, but no peripheral resistance, to thyroid hormone. (author)