Gliadin peptide P31-43 localises to endocytic vesicles and interferes with their maturation.

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Maria Vittoria Barone

Full Text Available BACKGROUND: Celiac Disease (CD is both a frequent disease (1:100 and an interesting model of a disease induced by food. It consists in an immunogenic reaction to wheat gluten and glutenins that has been found to arise in a specific genetic background; however, this reaction is still only partially understood. Activation of innate immunity by gliadin peptides is an important component of the early events of the disease. In particular the so-called "toxic" A-gliadin peptide P31-43 induces several pleiotropic effects including Epidermal Growth Factor Receptor (EGFR-dependent actin remodelling and proliferation in cultured cell lines and in enterocytes from CD patients. These effects are mediated by delayed EGFR degradation and prolonged EGFR activation in endocytic vesicles. In the present study we investigated the effects of gliadin peptides on the trafficking and maturation of endocytic vesicles. METHODS/PRINCIPAL FINDINGS: Both P31-43 and the control P57-68 peptide labelled with fluorochromes were found to enter CaCo-2 cells and interact with the endocytic compartment in pulse and chase, time-lapse, experiments. P31-43 was localised to vesicles carrying early endocytic markers at time points when P57-68-carrying vesicles mature into late endosomes. In time-lapse experiments the trafficking of P31-43-labelled vesicles was delayed, regardless of the cargo they were carrying. Furthermore in celiac enterocytes, from cultured duodenal biopsies, P31-43 trafficking is delayed in early endocytic vesicles. A sequence similarity search revealed that P31-43 is strikingly similar to Hrs, a key molecule regulating endocytic maturation. A-gliadin peptide P31-43 interfered with Hrs correct localisation to early endosomes as revealed by western blot and immunofluorescence microscopy. CONCLUSIONS: P31-43 and P57-68 enter cells by endocytosis. Only P31-43 localises at the endocytic membranes and delays vesicle trafficking by interfering with Hrs

Differential effects of EGFR ligands on endocytic sorting of the receptor

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Roepstorff, Kirstine; Grandal, Michael Vibo; Henriksen, Lasse

2009-01-01

signalling and is a more potent mitogen than EGF. In addition to EGF and TGF-alpha, five EGFR ligands have been identified. Although many of these ligands are upregulated in cancers, very little is known about their effect on EGFR trafficking. We have compared the effect of six different ligands on endocytic...... trafficking of EGFR. We find that, whereas they all stimulate receptor internalization, they have very diverse effects on endocytic sorting. Heparin-binding EGF-like growth factor and Betacellulin target all EGFRs for lysosomal degradation. In contrast, TGF-alpha and epiregulin lead to complete receptor...

A Coincidence Detection Mechanism Controls PX-BAR Domain-Mediated Endocytic Membrane Remodeling via an Allosteric Structural Switch.

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Lo, Wen-Ting; Vujičić Žagar, Andreja; Gerth, Fabian; Lehmann, Martin; Puchkov, Dymtro; Krylova, Oxana; Freund, Christian; Scapozza, Leonardo; Vadas, Oscar; Haucke, Volker

2017-11-20

Clathrin-mediated endocytosis occurs by bending and remodeling of the membrane underneath the coat. Bin-amphiphysin-rvs (BAR) domain proteins are crucial for endocytic membrane remodeling, but how their activity is spatiotemporally controlled is largely unknown. We demonstrate that the membrane remodeling activity of sorting nexin 9 (SNX9), a late-acting endocytic PX-BAR domain protein required for constriction of U-shaped endocytic intermediates, is controlled by an allosteric structural switch involving coincident detection of the clathrin adaptor AP2 and phosphatidylinositol-3,4-bisphosphate (PI(3,4)P 2 ) at endocytic sites. Structural, biochemical, and cell biological data show that SNX9 is autoinhibited in solution. Binding to PI(3,4)P 2 via its PX-BAR domain, and concomitant association with AP2 via sequences in the linker region, releases SNX9 autoinhibitory contacts to enable membrane constriction. Our results reveal a mechanism for restricting the latent membrane remodeling activity of BAR domain proteins to allow spatiotemporal coupling of membrane constriction to the progression of the endocytic pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Asymmetric segregation and self-renewal of hematopoietic stem and progenitor cells with endocytic Ap2a2.

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Ting, Stephen B; Deneault, Eric; Hope, Kristin; Cellot, Sonia; Chagraoui, Jalila; Mayotte, Nadine; Dorn, Jonas F; Laverdure, Jean-Philippe; Harvey, Michael; Hawkins, Edwin D; Russell, Sarah M; Maddox, Paul S; Iscove, Norman N; Sauvageau, Guy

2012-03-15

The stem cell-intrinsic model of self-renewal via asymmetric cell division (ACD) posits that fate determinants be partitioned unequally between daughter cells to either activate or suppress the stemness state. ACD is a purported mechanism by which hematopoietic stem cells (HSCs) self-renew, but definitive evidence for this cellular process remains open to conjecture. To address this issue, we chose 73 candidate genes that function within the cell polarity network to identify potential determinants that may concomitantly alter HSC fate while also exhibiting asymmetric segregation at cell division. Initial gene-expression profiles of polarity candidates showed high and differential expression in both HSCs and leukemia stem cells. Altered HSC fate was assessed by our established in vitro to in vivo screen on a subcohort of candidate polarity genes, which revealed 6 novel positive regulators of HSC function: Ap2a2, Gpsm2, Tmod1, Kif3a, Racgap1, and Ccnb1. Interestingly, live-cell videomicroscopy of the endocytic protein AP2A2 shows instances of asymmetric segregation during HSC/progenitor cell cytokinesis. These results contribute further evidence that ACD is functional in HSC self-renewal, suggest a role for Ap2a2 in HSC activity, and provide a unique opportunity to prospectively analyze progeny from HSC asymmetric divisions.

Endocytic Pathways Involved in Filovirus Entry: Advances, Implications and Future Directions

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Suchita Bhattacharyya

2012-12-01

Full Text Available Detailed knowledge of the host-virus interactions that accompany filovirus entry into cells is expected to identify determinants of viral virulence and host range, and to yield targets for the development of antiviral therapeutics. While it is generally agreed that filovirus entry into the host cytoplasm requires viral internalization into acidic endosomal compartments and proteolytic cleavage of the envelope glycoprotein by endo/lysosomal cysteine proteases, our understanding of the specific endocytic pathways co-opted by filoviruses remains limited. This review addresses the current knowledge on cellular endocytic pathways implicated in filovirus entry, highlights the consensus as well as controversies, and discusses important remaining questions.

Safeguards of Neurotransmission: Endocytic Adaptors as Regulators of Synaptic Vesicle Composition and Function

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Natalie Kaempf

2017-10-01

Full Text Available Communication between neurons relies on neurotransmitters which are released from synaptic vesicles (SVs upon Ca2+ stimuli. To efficiently load neurotransmitters, sense the rise in intracellular Ca2+ and fuse with the presynaptic membrane, SVs need to be equipped with a stringently controlled set of transmembrane proteins. In fact, changes in SV protein composition quickly compromise neurotransmission and most prominently give rise to epileptic seizures. During exocytosis SVs fully collapse into the presynaptic membrane and consequently have to be replenished to sustain neurotransmission. Therefore, surface-stranded SV proteins have to be efficiently retrieved post-fusion to be used for the generation of a new set of fully functional SVs, a process in which dedicated endocytic sorting adaptors play a crucial role. The question of how the precise reformation of SVs is achieved is intimately linked to how SV membranes are retrieved. For a long time both processes were believed to be two sides of the same coin since Clathrin-mediated endocytosis (CME, the proposed predominant SV recycling mode, will jointly retrieve SV membranes and proteins. However, with the recent proposal of Clathrin-independent SV recycling pathways SV membrane retrieval and SV reformation turn into separable events. This review highlights the progress made in unraveling the molecular mechanisms mediating the high-fidelity retrieval of SV proteins and discusses how the gathered knowledge about SV protein recycling fits in with the new notions of SV membrane endocytosis.

Localization and role of MYO-1, an endocytic protein in hyphae of Neurospora crassa.

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Lara-Rojas, Fernando; Bartnicki-García, Salomón; Mouriño-Pérez, Rosa R

2016-03-01

The subapical endocytic collar is a prominent feature of hyphae of Neurospora crassa. It comprises a dynamic collection of actin patches associated with a number of proteins required for endocytosis, namely, ARP-2/3 complex, fimbrin, coronin, etc. We presently show that MYO-1 is another key component of this endocytic collar. A myo-1 sequence was identified in the genome of N. crassa and used it to generate a strain with a myo-1-sgfp allele under the ccg1 promoter. Examination of living hyphae by confocal microscopy, revealed MYO-1-GFP located mainly as a dynamic collection of small patches arranged in collar-like fashion in the hyphal subapex. Dual tagging showed MYO-1-GFP partially colocalized with two other endocytic proteins, fimbrin and coronin. MYO-1 was also present during septum formation. By recovering a viable strain, albeit severely inhibited, after deletion of myo-1, it was possible to investigate the phenotypic consequences of the elimination of MYO-1. Deletion of myo-1 caused a severe reduction in growth rate (95%), near absence of aerial mycelium and no conidiation. A reduced uptake of the lipophilic dye FM4-64 indicated a deficiency in endocytosis in the Δmyo-1 mutant. Hyphae were produced by the Δmyo-1 mutant but their morphogenesis was severely affected; hyphal morphology was distorted displaying irregular periods of isotropic and polarized growth. The morphological alterations were accompanied, and presumably caused, by a disruption in the organization and dynamics of a myosin-deprived actin cytoskeleton that, ultimately, compromised the stability and function of the Spitzenkörper as a vesicle supply center. Copyright © 2016 Elsevier Inc. All rights reserved.

The minute virus of mice exploits different endocytic pathways for cellular uptake

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Garcin, Pierre O.; Panté, Nelly

2015-01-01

The minute virus of mice, prototype strain (MVMp), is a non-enveloped, single-stranded DNA virus of the family Parvoviridae. Unlike other parvoviruses, the mechanism of cellular uptake of MVMp has not been studied in detail. We analyzed MVMp endocytosis in mouse LA9 fibroblasts and a tumor cell line derived from epithelial–mesenchymal transition through polyomavirus middle T antigen transformation in transgenic mice. By a combination of immunofluorescence and electron microscopy, we found that MVMp endocytosis occurs at the leading edge of migrating cells in proximity to focal adhesion sites. By using drug inhibitors of various endocytic pathways together with immunofluorescence microscopy and flow cytometry analysis, we discovered that MVMp can use a number of endocytic pathways, depending on the host cell type. At least three different mechanisms were identified: clathrin-, caveolin-, and clathrin-independent carrier-mediated endocytosis, with the latter occurring in transformed cells but not in LA9 fibroblasts. - Highlights: • MVMp uptake takes place at the leading edge of migrating cells. • MVMp exploits a variety of endocytic pathways. • MVMp could use clathrin- and caveolin-mediated endocytosis. • MVMp could also use clathrin-independent carriers for cellular uptake

The minute virus of mice exploits different endocytic pathways for cellular uptake

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Garcin, Pierre O.; Panté, Nelly, E-mail: pante@zoology.ubc.ca

2015-08-15

The minute virus of mice, prototype strain (MVMp), is a non-enveloped, single-stranded DNA virus of the family Parvoviridae. Unlike other parvoviruses, the mechanism of cellular uptake of MVMp has not been studied in detail. We analyzed MVMp endocytosis in mouse LA9 fibroblasts and a tumor cell line derived from epithelial–mesenchymal transition through polyomavirus middle T antigen transformation in transgenic mice. By a combination of immunofluorescence and electron microscopy, we found that MVMp endocytosis occurs at the leading edge of migrating cells in proximity to focal adhesion sites. By using drug inhibitors of various endocytic pathways together with immunofluorescence microscopy and flow cytometry analysis, we discovered that MVMp can use a number of endocytic pathways, depending on the host cell type. At least three different mechanisms were identified: clathrin-, caveolin-, and clathrin-independent carrier-mediated endocytosis, with the latter occurring in transformed cells but not in LA9 fibroblasts. - Highlights: • MVMp uptake takes place at the leading edge of migrating cells. • MVMp exploits a variety of endocytic pathways. • MVMp could use clathrin- and caveolin-mediated endocytosis. • MVMp could also use clathrin-independent carriers for cellular uptake.

Endocytic Pathways Used by Andes Virus to Enter Primary Human Lung Endothelial Cells.

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Cheng-Feng Chiang

Full Text Available Andes virus (ANDV is the major cause of hantavirus pulmonary syndrome (HPS in South America. Despite a high fatality rate (up to 40%, no vaccines or antiviral therapies are approved to treat ANDV infection. To understand the role of endocytic pathways in ANDV infection, we used 3 complementary approaches to identify cellular factors required for ANDV entry into human lung microvascular endothelial cells. We screened an siRNA library targeting 140 genes involved in membrane trafficking, and identified 55 genes required for ANDV infection. These genes control the major endocytic pathways, endosomal transport, cell signaling, and cytoskeleton rearrangement. We then used infectious ANDV and retroviral pseudovirions to further characterize the possible involvement of 9 of these genes in the early steps of ANDV entry. In addition, we used markers of cellular endocytosis along with chemical inhibitors of known endocytic pathways to show that ANDV uses multiple routes of entry to infect target cells. These entry mechanisms are mainly clathrin-, dynamin-, and cholesterol-dependent, but can also occur via a clathrin-independent manner.

The HPV16 E5 oncogene inhibits endocytic trafficking

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Thomsen, P; van Deurs, B; Norrild, B

2000-01-01

fibroblasts to study the effects of E5. Various endocytic markers including the pH-sensitive probe DM-NERF coupled to dextran, TransFluoSpheres and TRITC-concanavalin A, were applied. In E5-transfected cells, none of these markers colocalized with the membrane permeable probe LysoTracker Red, which...

Release of canine parvovirus from endocytic vesicles

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Suikkanen, Sanna; Antila, Mia; Jaatinen, Anne; Vihinen-Ranta, Maija; Vuento, Matti

2003-01-01

Canine parvovirus (CPV) is a small nonenveloped virus with a single-stranded DNA genome. CPV enters cells by clathrin-mediated endocytosis and requires an acidic endosomal step for productive infection. Virion contains a potential nuclear localization signal as well as a phospholipase A 2 like domain in N-terminus of VP1. In this study we characterized the role of PLA 2 activity on CPV entry process. PLA 2 activity of CPV capsids was triggered in vitro by heat or acidic pH. PLA 2 inhibitors inhibited the viral proliferation suggesting that PLA 2 activity is needed for productive infection. The N-terminus of VP1 was exposed during the entry, suggesting that PLA 2 activity might have a role during endocytic entry. The presence of drugs modifying endocytosis (amiloride, bafilomycin A 1 , brefeldin A, and monensin) caused viral proteins to remain in endosomal/lysosomal vesicles, even though the drugs were not able to inhibit the exposure of VP1 N-terminal end. These results indicate that the exposure of N-terminus of VP1 alone is not sufficient to allow CPV to proliferate. Some other pH-dependent changes are needed for productive infection. In addition to blocking endocytic entry, amiloride was able to block some postendocytic steps. The ability of CPV to permeabilize endosomal membranes was demonstrated by feeding cells with differently sized rhodamine-conjugated dextrans together with the CPV in the presence or in the absence of amiloride, bafilomycin A 1 , brefeldin A, or monensin. Dextran with a molecular weight of 3000 was released from vesicles after 8 h of infection, while dextran with a molecular weight of 10,000 was mainly retained in vesicles. The results suggest that CPV infection does not cause disruption of endosomal vesicles. However, the permeability of endosomal membranes apparently changes during CPV infection, probably due to the PLA 2 activity of the virus. These results suggest that parvoviral PLA 2 activity is essential for productive infection and

The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses.

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Gräßel, Linda; Fast, Laura Aline; Scheffer, Konstanze D; Boukhallouk, Fatima; Spoden, Gilles A; Tenzer, Stefan; Boller, Klaus; Bago, Ruzica; Rajesh, Sundaresan; Overduin, Michael; Berditchevski, Fedor; Florin, Luise

2016-08-31

Human papillomaviruses enter host cells via a clathrin-independent endocytic pathway involving tetraspanin proteins. However, post-endocytic trafficking required for virus capsid disassembly remains unclear. Here we demonstrate that the early trafficking pathway of internalised HPV particles involves tetraspanin CD63, syntenin-1 and ESCRT-associated adaptor protein ALIX. Following internalisation, viral particles are found in CD63-positive endosomes recruiting syntenin-1, a CD63-interacting adaptor protein. Electron microscopy and immunofluorescence experiments indicate that the CD63-syntenin-1 complex controls delivery of internalised viral particles to multivesicular endosomes. Accordingly, infectivity of high-risk HPV types 16, 18 and 31 as well as disassembly and post-uncoating processing of viral particles was markedly suppressed in CD63 or syntenin-1 depleted cells. Our analyses also present the syntenin-1 interacting protein ALIX as critical for HPV infection and CD63-syntenin-1-ALIX complex formation as a prerequisite for intracellular transport enabling viral capsid disassembly. Thus, our results identify the CD63-syntenin-1-ALIX complex as a key regulatory component in post-endocytic HPV trafficking.

A Comparative Study on the Alterations of Endocytic Pathways in Multiple Lysosomal Storage Disorders.

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Rappaport, Jeff; Manthe, Rachel L; Solomon, Melani; Garnacho, Carmen; Muro, Silvia

2016-02-01

Many cellular activities and pharmaceutical interventions involve endocytosis and delivery to lysosomes for processing. Hence, lysosomal processing defects can cause cell and tissue damage, as in lysosomal storage diseases (LSDs) characterized by lysosomal accumulation of undegraded materials. This storage causes endocytic and trafficking alterations, which exacerbate disease and hinder treatment. However, there have been no systematic studies comparing different endocytic routes in LSDs. Here, we used genetic and pharmacological models of four LSDs (type A Niemann-Pick, type C Niemann-Pick, Fabry, and Gaucher diseases) and evaluated the pinocytic and receptor-mediated activity of the clathrin-, caveolae-, and macropinocytic routes. Bulk pinocytosis was diminished in all diseases, suggesting a generic endocytic alteration linked to lysosomal storage. Fluid-phase (dextran) and ligand (transferrin) uptake via the clathrin route were lower for all LSDs. Fluid-phase and ligand (cholera toxin B) uptake via the caveolar route were both affected but less acutely in Fabry or Gaucher diseases. Epidermal growth factor-induced macropinocytosis was altered in Niemann-Pick cells but not other LSDs. Intracellular trafficking of ligands was also distorted in LSD versus wild-type cells. The extent of these endocytic alterations paralleled the level of cholesterol storage in disease cell lines. Confirming this, pharmacological induction of cholesterol storage in wild-type cells disrupted endocytosis, and model therapeutics restored uptake in proportion to their efficacy in attenuating storage. This suggests a proportional and reversible relationship between endocytosis and lipid (cholesterol) storage. By analogy, the accumulation of biological material in other diseases, or foreign material from drugs or their carriers, may cause similar deficits, warranting further investigation.

Endocytic pathways mediating oligomeric Aβ42 neurotoxicity

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Laxton Kevin

2010-05-01

Full Text Available Abstract Background One pathological hallmark of Alzheimer's disease (AD is amyloid plaques, composed primarily of amyloid-β peptide (Aβ. Over-production or diminished clearance of the 42 amino acid form of Aβ (Aβ42 in the brain leads to accumulation of soluble Aβ and plaque formation. Soluble oligomeric Aβ (oAβ has recently emerged to be as a likely proximal cause of AD. Results Here we demonstrate that endocytosis is critical in mediating oAβ42-induced neurotoxicity and intraneuronal accumulation of Aβ. Inhibition of clathrin function either with a pharmacological inhibitor, knock-down of clathrin heavy chain expression, or expression of the dominant-negative mutant of clathrin-assembly protein AP180 did not block oAβ42-induced neurotoxicity or intraneuronal accumulation of Aβ. However, inhibition of dynamin and RhoA by expression of dominant negative mutants reduced neurotoxicity and intraneuronal Aβ accumulation. Pharmacologic inhibition of the dynamin-mediated endocytic pathway by genistein also reduced neurotoxicity. Conclusions These data suggest that dynamin-mediated and RhoA-regulated endocytosis are integral steps for oligomeric Aβ42-induced neurotoxicity and intraneuronal Aβ accumulation.

Raft-dependent endocytic movement and intracellular cluster formation during T cell activation triggered by concanavalin A.

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Yabuuchi, Satomi; Endo, Satoshi; Baek, KeangOk; Hoshino, Kunihide; Tsujino, Yoshio; Vestergaard, Mun'delanji C; Takagi, Masahiro

2017-12-01

Certain food ingredients can stimulate the human immune system. A lectin, concanavalin A (ConA), from Canavalia ensiformis (jack bean) is one of the most well-known food-derived immunostimulants and mediates activation of cell-mediated immunity through T cell proliferation. Generally, T cell activation is known to be triggered by the interaction between T cells and antigen-presenting cells (APCs) via a juxtacrine (contact-dependent) signaling pathway. The mechanism has been well characterized and is referred to as formation of the immunological synapse (IS). We were interested in the mechanism behind the T cell activation by food-derived ConA which might be different from that of T cell activation by APCs. The purpose of this study was to characterize T cell activation by ConA with regard to (i) movement of raft domain, (ii) endocytic vesicular transport, (iii) the cytoskeleton (actin and microtubules), and (iv) cholesterol composition. We found that raft-dependent endocytic movement was important for T cell activation by ConA and this movement was dependent on actin, microtubules, and cholesterol. The T cell signaling mechanism triggered by ConA can be defined as endocrine signaling which is distinct from the activation process triggered by interaction between T cells and APCs by juxtacrine signaling. Therefore, we hypothesized that T cell activation by ConA includes both two-dimensional superficial raft movement on the membrane surface along actin filaments and three-dimensional endocytic movement toward the inside of the cell along microtubules. These findings are important for developing new methods for immune stimulation and cancer therapy based on the function of ConA. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Unique supply function equilibrium with capacity constraints

International Nuclear Information System (INIS)

Holmberg, Paer

2008-01-01

Consider a market where producers submit supply functions to a procurement auction with uncertain demand, e.g. an electricity auction. In the Supply Function Equilibrium (SFE), every firm commits to the supply function that maximises expected profit in the one-shot game given the supply functions of competitors. A basic weakness of the SFE is the presence of multiple equilibria. This paper shows that with (i) symmetric producers, (ii) perfectly inelastic demand, (iii) a price cap, and (iv) capacity constraints that bind with a positive probability, there exists a unique, symmetric SFE. (author)

Differential actions of the endocytic collagen receptor uPARAP/Endo180 and the collagenase MMP-2 in bone homeostasis

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Madsen, Daniel H; Jürgensen, Henrik J; Ingvarsen, Signe

2013-01-01

A well-coordinated remodeling of uncalcified collagen matrices is a pre-requisite for bone development and homeostasis. Collagen turnover proceeds through different pathways, either involving extracellular reactions exclusively, or being dependent on endocytic processes. Extracellular collagen...... degradation requires the action of secreted or membrane attached collagenolytic proteases, whereas the alternative collagen degradation pathway proceeds intracellularly after receptor-mediated uptake and delivery to the lysosomes. In this study we have examined the functional interplay between...

Probiotics promote endocytic allergen degradation in gut epithelial cells

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Song, Chun-Hua; Liu, Zhi-Qiang; Huang, Shelly; Zheng, Peng-Yuan; Yang, Ping-Chang

2012-01-01

Highlights: ► Knockdown of A20 compromised the epithelial barrier function. ► The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. ► Antigens transported across A20-deficient HT-29 monolayers conserved antigenicity. ► Probiotic proteins increased the expression of A20 in HT-29 cells. -- Abstract: Background and aims: Epithelial barrier dysfunction plays a critical role in the pathogenesis of allergic diseases; the mechanism is to be further understood. The ubiquitin E3 ligase A20 (A20) plays a role in the endocytic protein degradation in the cells. This study aims to elucidate the role of A20 in the maintenance of gut epithelial barrier function. Methods: Gut epithelial cell line, HT-29 cell, was cultured into monolayers to evaluate the barrier function in transwells. RNA interference was employed to knock down the A20 gene in HT-29 cells to test the role of A20 in the maintenance of epithelial barrier function. Probiotic derived proteins were extracted from the culture supernatants using to enhance the expression of A20 in HT-29 cells. Results: The results showed that the knockdown of A20 compromised the epithelial barrier function in HT-29 monolayers, mainly increased the intracellular permeability. The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Allergens collected from the transwell basal chambers of A20-deficient HT-29 monolayers still conserved functional antigenicity. Treating with probiotic derived proteins increased the expression of A20 in HT-29 cells and promote the barrier function. Conclusion: A20 plays an important role in the maintenance of epithelial barrier function as shown by HT-29 monolayer. Probiotic derived protein increases the expression of A20 and promote the HT-29 monolayer barrier function.

Probiotics promote endocytic allergen degradation in gut epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Song, Chun-Hua [Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou (China); Liu, Zhi-Qiang [Department of Gastroenterology, The Second Hospital, Zhengzhou University, Zhengzhou (China); Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON (Canada); Huang, Shelly [Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON (Canada); Zheng, Peng-Yuan, E-mail: medp7123@126.com [Department of Gastroenterology, The Second Hospital, Zhengzhou University, Zhengzhou (China); Yang, Ping-Chang, E-mail: yangp@mcmaster.ca [Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON (Canada)

2012-09-14

Highlights: Black-Right-Pointing-Pointer Knockdown of A20 compromised the epithelial barrier function. Black-Right-Pointing-Pointer The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Black-Right-Pointing-Pointer Antigens transported across A20-deficient HT-29 monolayers conserved antigenicity. Black-Right-Pointing-Pointer Probiotic proteins increased the expression of A20 in HT-29 cells. -- Abstract: Background and aims: Epithelial barrier dysfunction plays a critical role in the pathogenesis of allergic diseases; the mechanism is to be further understood. The ubiquitin E3 ligase A20 (A20) plays a role in the endocytic protein degradation in the cells. This study aims to elucidate the role of A20 in the maintenance of gut epithelial barrier function. Methods: Gut epithelial cell line, HT-29 cell, was cultured into monolayers to evaluate the barrier function in transwells. RNA interference was employed to knock down the A20 gene in HT-29 cells to test the role of A20 in the maintenance of epithelial barrier function. Probiotic derived proteins were extracted from the culture supernatants using to enhance the expression of A20 in HT-29 cells. Results: The results showed that the knockdown of A20 compromised the epithelial barrier function in HT-29 monolayers, mainly increased the intracellular permeability. The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Allergens collected from the transwell basal chambers of A20-deficient HT-29 monolayers still conserved functional antigenicity. Treating with probiotic derived proteins increased the expression of A20 in HT-29 cells and promote the barrier function. Conclusion: A20 plays an important role in the maintenance of epithelial barrier function as shown by HT-29 monolayer. Probiotic derived protein increases the expression of A20 and promote the HT-29 monolayer barrier function.

Loss of endocytic clathrin-coated pits upon acute depletion of phosphatidylinositol 4,5-bisphosphate.

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Zoncu, Roberto; Perera, Rushika M; Sebastian, Rafael; Nakatsu, Fubito; Chen, Hong; Balla, Tamas; Ayala, Guillermo; Toomre, Derek; De Camilli, Pietro V

2007-03-06

Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)], a phosphoinositide concentrated predominantly in the plasma membrane, binds endocytic clathrin adaptors, many of their accessory factors, and a variety of actin-regulatory proteins. Here we have used fluorescent fusion proteins and total internal reflection fluorescence microscopy to investigate the effect of acute PI(4,5)P(2) breakdown on the dynamics of endocytic clathrin-coated pit components and of the actin regulatory complex, Arp2/3. PI(4,5)P(2) breakdown was achieved by the inducible recruitment to the plasma membrane of an inositol 5-phosphatase module through the rapamycin/FRB/FKBP system or by treatment with ionomycin. PI(4,5)P(2) depletion resulted in a dramatic loss of clathrin puncta, which correlated with a massive dissociation of endocytic adaptors from the plasma membrane. Remaining clathrin spots at the cell surface had only weak fluorescence and were static over time. Dynamin and the p20 subunit of the Arp2/3 actin regulatory complex, which were concentrated at late-stage clathrin-coated pits and in lamellipodia, also dissociated from the plasma membrane, and these changes correlated with an arrest of motility at the cell edge. These findings demonstrate the critical importance of PI(4,5)P(2) in clathrin coat dynamics and Arp2/3-dependent actin regulation.

Rab14 and its exchange factor FAM116 link endocytic recycling and adherens junction stability in migrating cells.

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Linford, Andrea; Yoshimura, Shin-ichiro; Nunes Bastos, Ricardo; Langemeyer, Lars; Gerondopoulos, Andreas; Rigden, Daniel J; Barr, Francis A

2012-05-15

Rab GTPases define the vesicle trafficking pathways underpinning cell polarization and migration. Here, we find that Rab4, Rab11, and Rab14 and the candidate Rab GDP-GTP exchange factors (GEFs) FAM116A and AVL9 are required for cell migration. Rab14 and its GEF FAM116A localize to and act on an intermediate compartment of the transferrin-recycling pathway prior to Rab11 and after Rab5 and Rab4. This Rab14 intermediate recycling compartment has specific functions in migrating cells discrete from early and recycling endosomes. Rab14-depleted cells show increased N-cadherin levels at junctional complexes and cannot resolve cell-cell junctions. This is due to decreased shedding of cell-surface N-cadherin by the ADAM family protease ADAM10/Kuzbanian. In FAM116A- and Rab14-depleted cells, ADAM10 accumulates in a transferrin-positive endocytic compartment, and the cell-surface level of ADAM10 is correspondingly reduced. FAM116 and Rab14 therefore define an endocytic recycling pathway needed for ADAM protease trafficking and regulation of cell-cell junctions. Copyright © 2012 Elsevier Inc. All rights reserved.

Effector protein translocation by the Coxiella burnetii Dot/Icm type IV secretion system requires endocytic maturation of the pathogen-occupied vacuole.

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Hayley J Newton

Full Text Available The human pathogen Coxiella burnetii encodes a type IV secretion system called Dot/Icm that is essential for intracellular replication. The Dot/Icm system delivers bacterial effector proteins into the host cytosol during infection. The effector proteins delivered by C. burnetii are predicted to have important functions during infection, but when these proteins are needed during infection has not been clearly defined. Here, we use a reporter system consisting of fusion proteins that have a β-lactamase enzyme (BlaM fused to C. burnetii effector proteins to study protein translocation by the Dot/Icm system. Translocation of BlaM fused to the effector proteins CBU0077, CBU1823 and CBU1524 was not detected until 8-hours after infection of HeLa cells, which are permissive for C. burnetii replication. Translocation of these effector fusion proteins by the Dot/Icm system required acidification of the Coxiella-containing vacuole. Silencing of the host genes encoding the membrane transport regulators Rab5 or Rab7 interfered with effector translocation, which indicates that effectors are not translocated until bacteria traffic to a late endocytic compartment in the host cell. Similar requirements for effector translocation were discerned in bone marrow macrophages derived from C57BL/6 mice, which are primary cells that restrict the intracellular replication of C. burnetii. In addition to requiring endocytic maturation of the vacuole for Dot/Icm-mediated translocation of effectors, bacterial transcription was required for this process. Thus, translocation of effector proteins by the C. burnetii Dot/Icm system occurs after acidification of the CCV and maturation of this specialized organelle to a late endocytic compartment. This indicates that creation of the specialized vacuole in which C. burnetii replicates represents a two-stage process mediated initially by host factors that regulate endocytic maturation and then by bacterial effectors delivered into

Zebrafish kidney phagocytes utilize macropinocytosis and Ca+-dependent endocytic mechanisms.

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Claudia Hohn

Full Text Available BACKGROUND: The innate immune response constitutes the first line of defense against invading pathogens and consists of a variety of immune defense mechanisms including active endocytosis by macrophages and granulocytes. Endocytosis can be used as a reliable measure of selective and non-selective mechanisms of antigen uptake in the early phase of an immune response. Numerous assays have been developed to measure this response in a variety of mammalian and fish species. The small size of the zebrafish has prevented the large-scale collection of monocytes/macrophages and granulocytes for these endocytic assays. METHODOLOGY/PRINCIPAL FINDINGS: Pooled zebrafish kidney hematopoietic tissues were used as a source of phagocytic cells for flow-cytometry based endocytic assays. FITC-Dextran, Lucifer Yellow and FITC-Edwardsiella ictaluri were used to evaluate selective and non-selective mechanisms of uptake in zebrafish phagocytes. CONCLUSIONS/SIGNIFICANCE: Zebrafish kidney phagocytes characterized as monocytes/macrophages, neutrophils and lymphocytes utilize macropinocytosis and Ca(2+-dependant endocytosis mechanisms of antigen uptake. These cells do not appear to utilize a mannose receptor. Heat-killed Edwardsiella ictaluri induces cytoskeletal interactions for internalization in zebrafish kidney monocytes/macrophages and granulocytes. The proposed method is easy to implement and should prove especially useful in immunological, toxicological and epidemiological research.

Localization of HCMV UL33 and US27 in endocytic compartments and viral membranes

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Fraile-Ramos, Alberto; Pelchen-Matthews, Annegret; Kledal, Thomas N

2002-01-01

and undergoes constitutive endocytosis and recycling. Here we studied the cellular distributions and trafficking of two other human cytomegalovirus chemokine receptor-like proteins, UL33 and US27, in transfected and human cytomegalovirus-infected cells. Immunofluorescence staining indicated that UL33 and US27......The human cytomegalovirus genome encodes four putative seven transmembrane domain chemokine receptor-like proteins. Although important in viral pathogenesis, little is known about the properties or functions of these proteins. We previously reported that US28 is located in endocytic vesicles......27 undergoes endocytosis. By immunogold labeling of cryosections and electron microscopy, UL33 was seen to localize to multivesicular bodies (MVBs or multivesicular endosomes). Electron microscopy analysis of human cytomegalovirus-infected cells showed that most virus particles wrapped individually...

Stochastic Modeling of the Clathrin-dependent and -independent Endocytic Pathways

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Deng, Hua; Dutta, Prashanta; Liu, Jin

2017-11-01

Endocytosis is one of the important processes that bioparticles use to enter the cells. During endocytosis the membrane-bound vesicles are formed by the invagination of plasma membrane as a result of interactions among many proteins and cytoskeletons. The clathrin-mediated endocytosis is one of the most significant form of endocytosis, where the dynamic assembly of clathrin-coated pits play a critical role. While herpes simplex virus-1 has recently shown to infect cell by a novel phagocytosis-like endocytic pathway where actin polymerization may facilitate the viral entry. In this work, we propose a stochastic model for both clathrin-dependent and -independent endocytic pathways based on Monte Carlo simulations. The important roles of clathrin coating and actin cytoskeleton as well as the impact of other biological parameters are studied. Our preliminary results indicate that there exist an intermediate particle size and ligand density that maximize the internalization efficiency. Below a critical size or surface ligand density, it is difficult for the entry of a single particle, which means clustering may needed for more efficient internalization. We also find that lower membrane bending rigidity may help promote the bioparticle entry. Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM122081.

Executive Functions Contribute Uniquely to Reading Competence in Minority Youth

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Jacobson, Lisa A.; Koriakin, Taylor; Lipkin, Paul; Boada, Richard; Frijters, Jan; Lovett, Maureen; Hill, Dina; Willcutt, Erik; Gottwald, Stephanie; Wolf, Maryanne; Bosson-Heenan, Joan; Gruen, Jeffrey R.; Mahone, E. Mark

2018-01-01

Competent reading requires various skills beyond those for basic word reading (i.e., core language skills, rapid naming, phonological processing). Contributing “higher-level” or domain-general processes include information processing speed and executive functions (working memory, strategic problem solving, attentional switching). Research in this area has relied on largely Caucasian samples, with limited representation of children from racial or ethnic minority groups. This study examined contributions of executive skills to reading competence in 761 children of minority backgrounds. Hierarchical linear regressions examined unique contributions of executive functions (EF) to word reading, fluency, and comprehension. EF contributed uniquely to reading performance, over and above reading-related language skills; working memory contributed uniquely to all components of reading; while attentional switching, but not problem solving, contributed to isolated and contextual word reading and reading fluency. Problem solving uniquely predicted comprehension, suggesting that this skill may be especially important for reading comprehension in minority youth. Attentional switching may play a unique role in development of reading fluency in minority youth, perhaps as a result of the increased demand for switching between spoken versus written dialects. Findings have implications for educational and clinical practice with regard to reading instruction, remedial reading intervention, and assessment of individuals with reading difficulty. PMID:26755569

Endocytic trafficking from the small intestinal brush border probed with FM dye

DEFF Research Database (Denmark)

Hansen, Gert H; Rasmussen, Karina; Niels-Christiansen, Lise-Lotte

2009-01-01

-linking galectins/intelectin, but little is known about the dynamic properties of this highly specialized membrane. Here, we probed the endocytic membrane trafficking from the brush border of organ cultured pig intestinal mucosal explants by use of a fixable, lipophilic FM dye. The fluorescent dye readily......, contributes to the overall permeability barrier of the gut. Key words: FM dye, small intestine, brush border, endocytosis....

Endocytic activity of Sertoli cells grown in bicameral culture chambers

International Nuclear Information System (INIS)

Dai, R.X.; Djakiew, D.; Dym, M.

1987-01-01

Immature rat Sertoli cells were cultured for 7 to 14 days on Millipore filters impregnated with a reconstituted basement membrane extract in dual-environment (bicameral) culture chambers. Electron microscopy of the cultured cells revealed the presence of rod-shaped mitochondria, Golgi apparatus, rough endoplasmic reticulum, and Sertoli-Sertoli tight junctions, typical of these cells in vivo. The endocytic activity of both the apical and basal surfaces of the Sertoli cells was examined by either adding alpha 2-macroglobulin (alpha 2-M) conjugated to 20 nm gold particles to the apical chamber or by adding 125 I labeled alpha 2-M to the basal chamber. During endocytosis from the apical surface of Sertoli cells, the alpha 2-M-gold particles were bound initially to coated pits and then internalized into coated vesicles within 5 minutes. After 10 minutes, the alpha 2-M-gold was found in multi-vesicular bodies (MVBs) and by 30 minutes it was present in the lysosomes. The proportion of alpha 2-M-gold found within endocytic cell organelles after 1 hour of uptake was used to estimate the approximate time that this ligand spent in each type of organelle. The alpha 2-M-gold was present in coated pits, coated vesicles, multivesicular bodies, and lysosomes for approximately 3, 11, 22, and 24 minutes, respectively. This indicates that the initial stages of endocytosis are rapid, whereas MVBs and lysosomes are relatively long-lived

Endocytic recycling via the TGN underlies the polarized hyphal mode of life.

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Hernández-González, Miguel; Bravo-Plaza, Ignacio; Pinar, Mario; de Los Ríos, Vivian; Arst, Herbert N; Peñalva, Miguel A

2018-04-01

Intracellular traffic in Aspergillus nidulans hyphae must cope with the challenges that the high rates of apical extension (1μm/min) and the long intracellular distances (>100 μm) impose. Understanding the ways in which the hyphal tip cell coordinates traffic to meet these challenges is of basic importance, but is also of considerable applied interest, as fungal invasiveness of animals and plants depends critically upon maintaining these high rates of growth. Rapid apical extension requires localization of cell-wall-modifying enzymes to hyphal tips. By combining genetic blocks in different trafficking steps with multidimensional epifluorescence microscopy and quantitative image analyses we demonstrate that polarization of the essential chitin-synthase ChsB occurs by indirect endocytic recycling, involving delivery/exocytosis to apices followed by internalization by the sub-apical endocytic collar of actin patches and subsequent trafficking to TGN cisternae, where it accumulates for ~1 min before being re-delivered to the apex by a RAB11/TRAPPII-dependent pathway. Accordingly, ChsB is stranded at the TGN by Sec7 inactivation but re-polarizes to the apical dome if the block is bypassed by a mutation in geaAgea1 that restores growth in the absence of Sec7. That polarization is independent of RAB5, that ChsB predominates at apex-proximal cisternae, and that upon dynein impairment ChsB is stalled at the tips in an aggregated endosome indicate that endocytosed ChsB traffics to the TGN via sorting endosomes functionally located upstream of the RAB5 domain and that this step requires dynein-mediated basipetal transport. It also requires RAB6 and its effector GARP (Vps51/Vps52/Vps53/Vps54), whose composition we determined by MS/MS following affinity chromatography purification. Ablation of any GARP component diverts ChsB to vacuoles and impairs growth and morphology markedly, emphasizing the important physiological role played by this pathway that, we propose, is central

Epigenetic modulation of the biophysical properties of drug-resistant cell lipids to restore drug transport and endocytic functions.

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Vijayaraghavalu, Sivakumar; Peetla, Chiranjeevi; Lu, Shan; Labhasetwar, Vinod

2012-09-04

In our recent studies exploring the biophysical characteristics of resistant cell lipids, and the role they play in drug transport, we demonstrated the difference of drug-resistant breast cancer cells from drug-sensitive cells in lipid composition and biophysical properties, suggesting that cancer cells acquire a drug-resistant phenotype through the alteration of lipid synthesis to inhibit intracellular drug transport to protect from cytotoxic effect. In cancer cells, epigenetic changes (e.g., DNA hypermethylation) are essential to maintain this drug-resistant phenotype. Thus, altered lipid synthesis may be linked to epigenetic mechanisms of drug resistance. We hypothesize that reversing DNA hypermethylation in resistant cells with an epigenetic drug could alter lipid synthesis, changing the cell membrane's biophysical properties to facilitate drug delivery to overcome drug resistance. Herein we show that treating drug-resistant breast cancer cells (MCF-7/ADR) with the epigenetic drug 5-aza-2'-deoxycytidine (decitabine) significantly alters cell lipid composition and biophysical properties, causing the resistant cells to acquire biophysical characteristics similar to those of sensitive cell (MCF-7) lipids. Following decitabine treatment, resistant cells demonstrated increased sphingomyelinase activity, resulting in a decreased sphingomyelin level that influenced lipid domain structures, increased membrane fluidity, and reduced P-glycoprotein expression. Changes in the biophysical characteristics of resistant cell lipids facilitated doxorubicin transport and restored endocytic function for drug delivery with a lipid-encapsulated form of doxorubicin, enhancing the drug efficacy. In conclusion, we have established a new mechanism for efficacy of an epigenetic drug, mediated through changes in lipid composition and biophysical properties, in reversing cancer drug resistance.

Intersectin goes nuclear: secret life of an endocytic protein.

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Alvisi, Gualtiero; Paolini, Lucia; Contarini, Andrea; Zambarda, Chiara; Di Antonio, Veronica; Colosini, Antonella; Mercandelli, Nicole; Timmoneri, Martina; Palù, Giorgio; Caimi, Luigi; Ricotta, Doris; Radeghieri, Annalisa

2018-04-27

Intersectin 1-short (ITSN1-s) is a 1220 amino acid ubiquitously expressed scaffold protein presenting a multidomain structure that allows to spatiotemporally regulate the functional interaction of a plethora of proteins. Besides its well-established role in endocytosis, ITSN1-s is involved in the regulation of cell signaling and is implicated in tumorigenesis processes, although the signaling pathways involved are still poorly understood. Here, we identify ITSN1-s as a nucleocytoplasmic trafficking protein. We show that, by binding to importin (IMP)α, a small fraction of ITSN1-s localizes in the cell nucleus at the steady state, where it preferentially associates with the nuclear envelope and interacts with lamin A/C. However, upon pharmacological ablation of chromosome region maintenance 1 (CRM-1)-dependent nuclear export pathway, the protein accumulates into the nucleus, thus revealing its moonlighting nature. Analysis of deletion mutants revealed that the coiled coil (CC) and Src homology (SH3) regions play the major role in its nucleocytoplasmic shuttling. While no evidence of nuclear localization signal (NLS) was detected in the CC region, a functional bipartite NLS was identified within the SH3D region of ITSN1-s (RKKNPGGWWEGELQARGKKRQIGW-1127), capable of conferring energy-dependent nuclear accumulation to reporter proteins and whose mutational ablation affects nuclear import of the whole SH3 region. Thus, ITSN1-s is an endocytic protein, which shuttles between the nucleus and the cytoplasm in a CRM-1- and IMPα-dependent fashion. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Endocytic down-regulation of ErbB2 is stimulated by cleavage of its C-terminus

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Lerdrup, Mads; Bruun, Silas; Grandal, Michael Vibo

2007-01-01

inhibition of HSP90 with geldanamycin this cleavage is accompanied by proteasome-dependent endocytosis of ErbB2. However, it is unknown whether C-terminal cleavage is linked to endocytosis. To study ErbB2 cleavage and endocytic trafficking, we fused yellow fluorescent protein (YFP) and cyan fluorescent...

Porcine sialoadhesin (CD169/Siglec-1 is an endocytic receptor that allows targeted delivery of toxins and antigens to macrophages.

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Peter L Delputte

Full Text Available Sialoadhesin is exclusively expressed on specific subpopulations of macrophages. Since sialoadhesin-positive macrophages are involved in inflammatory autoimmune diseases, such as multiple sclerosis, and potentially in the generation of immune responses, targeted delivery of drugs, toxins or antigens via sialoadhesin-specific immunoconjugates may prove a useful therapeutic strategy. Originally, sialoadhesin was characterized as a lymphocyte adhesion molecule, though recently its involvement in internalization of sialic acid carrying pathogens was shown, suggesting that sialoadhesin is an endocytic receptor. In this report, we show that porcine sialoadhesin-specific antibodies and F(ab'₂ fragments trigger sialoadhesin internalization, both in primary porcine macrophages and in cells expressing recombinant porcine sialoadhesin. Using chemical inhibitors, double immunofluorescence stainings and dominant-negative constructs, porcine sialoadhesin internalization was shown to be clathrin- and Eps15-dependent and to result in targeting to early endosomes but not lysosomes. Besides characterizing the sialoadhesin endocytosis mechanism, two sialoadhesin-specific immunoconjugates were evaluated. We observed that porcine sialoadhesin-specific immunotoxins efficiently kill sialoadhesin-expressing macrophages. Furthermore, porcine sialoadhesin-specific albumin immunoconjugates were shown to be internalized in macrophages and immunization with these immunoconjugates resulted in a rapid and robust induction of albumin-specific antibodies, this compared to immunization with albumin alone. Together, these data expand sialoadhesin functionality and show that it can function as an endocytic receptor, a feature that cannot only be misused by sialic acid carrying pathogens, but that may also be used for specific targeting of toxins or antigens to sialoadhesin-expressing macrophages.

Bcl-xL regulates CD1d-mediated antigen presentation to NKT cells by altering CD1d trafficking through the endocytic pathway.

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Subrahmanyam, Priyanka B; Carey, Gregory B; Webb, Tonya J

2014-09-01

NKT cells are a unique subset of T cells that recognize glycolipid Ags presented in the context of CD1d molecules. NKT cells mount strong antitumor responses and are a major focus in developing effective cancer immunotherapy. It is known that CD1d molecules are constantly internalized from the cell surface, recycled through the endocytic compartments, and re-expressed on the cell surface. However, little is known about the regulation of CD1d-mediated Ag processing and presentation in B cell lymphoma. Prosurvival factors of the Bcl-2 family, such as Bcl-xL, are often upregulated in B cell lymphomas and are intimately linked to sphingolipid metabolism, as well as the endocytic compartments. We hypothesized that Bcl-xL can regulate CD1d-mediated Ag presentation to NKT cells. We found that overexpression or induction of Bcl-xL led to increased Ag presentation to NKT cells. Conversely, the inhibition or knockdown of Bcl-xL led to decreased NKT cell activation. Furthermore, knockdown of Bcl-xL resulted in the loss of CD1d trafficking to lysosome-associated membrane protein 1(+) compartments. Rab7, a late endosomal protein, was upregulated and CD1d molecules accumulated in the Rab7(+) late endosomal compartment. These results demonstrate that Bcl-xL regulates CD1d-mediated Ag processing and presentation to NKT cells by altering the late endosomal compartment and changing the intracellular localization of CD1d. Copyright © 2014 by The American Association of Immunologists, Inc.

Unique associations between young adult men's emotional functioning and their body dissatisfaction and disordered eating.

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Griffiths, Scott; Angus, Douglas; Murray, Stuart B; Touyz, Stephen

2014-03-01

Research on emotional functioning, body dissatisfaction, and disordered eating in males is predominated by studies of negative affect and emotion regulation. Other aspects of emotional functioning, namely emotion recognition and attentional biases toward emotional stimuli, have received little empirical attention. The present study investigated the unique associations between different aspects of men's emotional functioning and their disordered eating attitudes, muscularity dissatisfaction, and body fat dissatisfaction. Results from 132 male undergraduates showed that muscularity dissatisfaction was uniquely associated with both emotion regulation difficulties and an attentional bias toward rejecting faces. Body fat dissatisfaction was not uniquely associated with any aspect of emotional functioning. Disordered eating was uniquely associated with emotion regulation difficulties. Collectively, the results indicate differences in the patterns of associations between men's emotional functioning and their body dissatisfaction and disordered eating. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mutational analysis of the yeast TRAPP subunit Trs20p identifies roles in endocytic recycling and sporulation.

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Hichem Mahfouz

Full Text Available Trs20p is a subunit of the evolutionarily conserved TRAPP (TRAnsport Protein Particle complex that mediates various aspects of membrane trafficking. Three TRAPP complexes have been identified in yeast with roles in ER-to-Golgi trafficking, post-Golgi and endosomal-to-Golgi transport and in autophagy. The role of Trs20p, which is essential for viability and a component of all three complexes, and how it might function within each TRAPP complex, has not been clarified to date. To begin to address the role of Trs20p we generated different mutants by random mutagenesis but, surprisingly, no defects were observed in diverse anterograde transport pathways or general secretion in Trs20 temperature-sensitive mutants. Instead, mutation of Trs20 led to defects in endocytic recycling and a block in sporulation/meiosis. The phenotypes of different mutants appear to be separable suggesting that the mutations affect the function of Trs20 in different TRAPP complexes.

Porphyromonas gingivalis Outer Membrane Vesicles Enter Human Epithelial Cells via an Endocytic Pathway and Are Sorted to Lysosomal Compartments ▿

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Furuta, Nobumichi; Tsuda, Kayoko; Omori, Hiroko; Yoshimori, Tamotsu; Yoshimura, Fuminobu; Amano, Atsuo

2009-01-01

Porphyromonas gingivalis, a periodontal pathogen, secretes outer membrane vesicles (MVs) that contain major virulence factors, including major fimbriae and proteases termed gingipains, although it is not confirmed whether MVs enter host cells. In this study, we analyzed the mechanisms involved in the interactions of P. gingivalis MVs with human epithelial cells. Our results showed that MVs swiftly adhered to HeLa and immortalized human gingival epithelial cells in a fimbria-dependent manner and then entered via a lipid raft-dependent endocytic pathway. The intracellular MVs were subsequently routed to early endosome antigen 1-associated compartments and then were sorted to lysosomal compartments within 90 min, suggesting that intracellular MVs were ultimately degraded by the cellular digestive machinery. However, P. gingivalis MVs remained there for over 24 h and significantly induced acidified compartment formation after being taken up by the cellular digestive machinery. In addition, MV entry was shown to be mediated by a novel pathway for transmission of bacterial products into host cells, a Rac1-regulated pinocytic pathway that is independent of caveolin, dynamin, and clathrin. Our findings indicate that P. gingivalis MVs efficiently enter host cells via an endocytic pathway and survive within the endocyte organelles for an extended period, which provides better understanding of the role of MVs in the etiology of periodontitis. PMID:19651865

Pre-cancerous changes in urothelial endocytic vesicle leakage, fatty acid composition, and As and associated element concentrations after arsenic exposure

International Nuclear Information System (INIS)

Grasso, E.J.; Bongiovanni, G.A.; Perez, R.D.; Calderon, R.O.

2011-01-01

The urothelium covering the luminal surface of the urinary bladder has developed an efficient permeability barrier that protects it against the back-flow of toxins eliminated in the urine. The subapical endocytic vesicles containing the urinary bladder fluid phase are formed during the micturition cycle by endocytosis processes of the superficial cells. In normal conditions, the permeability barrier of the endocytic vesicles blocks the passage of the fluid phase to the cellular cytoplasm and the fluid is recycled to the bladder lumen. The aim of this work was to investigate the alteration of the endocytic vesicle membrane permeability barrier to toxins such as iAs (inorganic arsenic) administered in drinking water. By using an induced endocytosis model and the fluorescence requenching technique, it is shown that the exposure of rats to ingestion of water containing iAs not only induced pre-cancerous morphological changes, but allowed the differential leakage of an endocytosed fluorescent marker, HPTS, and its quencher, DPX, (hydroxypyrene-1,3,6-trisulfonic acid and p-xylene-bis-pyridinium bromide, respectively) out of the vesicular lumen. The leakage of the cationic DPX was almost complete, while the release of the anionic HPTS molecule was partial and higher in arsenic-treated-rats than in controls. Such membrane alteration would allow the toxins to elude the permeability barrier and to leak out of the endocytic vesicles, thus establishing a 'bypass' to the permeability barrier. The retention of As in the urinary bladder, assessed by synchrotron radiation X-ray fluorescence spectrometry (SR-μXRF), was lower than the kidney accumulation of arsenic previously observed by our group and was accompanied by altered concentrations of K, Ca, Fe, Cu and Zn, all ions related to cellular metabolism. The results support the hypothesis that low amounts of endocytosed As can accumulate in the interior of the urothelial superficial cells and initiate the cytotoxic effects

Endocytic pathway rapidly delivers internalized molecules to lysosomes: an analysis of vesicle trafficking, clustering and mass transfer.

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Pangarkar, Chinmay; Dinh, Anh-Tuan; Mitragotri, Samir

2012-08-20

Lysosomes play a critical role in intracellular drug delivery. For enzyme-based therapies, they represent a potential target site whereas for nucleic acid or many protein drugs, they represent the potential degradation site. Either way, understanding the mechanisms and processes involved in routing of materials to lysosomes after cellular entry is of high interest to the field of drug delivery. Most therapeutic cargoes other than small hydrophobic molecules enter the cells through endocytosis. Endocytosed cargoes are routed to lysosomes via microtubule-based transport and are ultimately shared by various lysosomes via tethering and clustering of endocytic vesicles followed by exchange of their contents. Using a combined experimental and numerical approach, here we studied the rates of mass transfer into and among the endocytic vesicles in a model cell line, 3T3 fibroblasts. In order to understand the relationship of mass transfer with microtubular transport and vesicle clustering, we varied both properties through various pharmacological agents. At the same time, microtubular transport and vesicle clustering were modeled through diffusion-advection equations and the Smoluchowski equations, respectively. Our analysis revealed that the rate of mass transfer is optimally related to microtubular transport and clustering properties of vesicles. Further, the rate of mass transfer is highest in the innate state of the cell. Any perturbation to either microtubular transport or vesicle aggregation led to reduced mass transfer to lysosome. These results suggest that in the absence of an external intervention the endocytic pathway appears to maximize molecular delivery to lysosomes. Strategies are discussed to reduce mass transfer to lysosomes so as to extend the residence time of molecules in endosomes or late endosomes, thus potentially increasing the likelihood of their escape before disposition in the lysosomes. Copyright © 2012 Elsevier B.V. All rights reserved.

Neratinib induces ErbB2 ubiquitylation and endocytic degradation via HSP90 dissociation in breast cancer cells.

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Zhang, Yingqiu; Zhang, Jinrui; Liu, Congcong; Du, Sha; Feng, Lu; Luan, Xuelin; Zhang, Yayun; Shi, Yulin; Wang, Taishu; Wu, Yue; Cheng, Wei; Meng, Songshu; Li, Man; Liu, Han

2016-11-28

Receptor tyrosine kinase ErbB2/HER2 is frequently observed to be overexpressed in human cancers, leading to over activation of downstream signaling modules. HER2 positive is a major type of breast cancer for which ErbB2 targeting is already proving to be an effective therapeutic strategy. Apart from antibodies against ErbB2, the small molecule tyrosine kinase inhibitor lapatinib has had successful clinical outcomes, and other inhibitors such as neratinib are currently undergoing clinical investigations. In this study we report the effects of lapatinib and neratinib on the mRNA and protein levels of the ErbB2 receptor. We provide evidence that neratinib-induced down regulation of ErbB2 occurs through ubiquitin-mediated endocytic sorting and lysosomal degradation. At the mechanistic level, neratinib treatment leads to HSP90 release from ErbB2 and its subsequent ubiquitylation and endocytic degradation. Our findings provide novel insights into the mechanism of ErbB2 inhibition by neratinib. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The late endocytic Rab39a GTPase regulates the interaction between multivesicular bodies and chlamydial inclusions.

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Gambarte Tudela, Julian; Capmany, Anahi; Romao, Maryse; Quintero, Cristian; Miserey-Lenkei, Stephanie; Raposo, Graca; Goud, Bruno; Damiani, Maria Teresa

2015-08-15

Given their obligate intracellular lifestyle, Chlamydia trachomatis ensure that they have access to multiple host sources of essential lipids by interfering with vesicular transport. These bacteria hijack Rab6-, Rab11- and Rab14-controlled trafficking pathways to acquire sphingomyelin from the Golgi complex. Another important source of sphingolipids, phospholipids and cholesterol are multivesicular bodies (MVBs). Despite their participation in chlamydial inclusion development and bacterial replication, the molecular mechanisms mediating the interaction between MVBs and chlamydial inclusions remain unknown. In the present study, we demonstrate that Rab39a labels a subset of late endocytic vesicles - mainly MVBs - that move along microtubules. Moreover, Rab39a is actively recruited to chlamydial inclusions throughout the pathogen life cycle by a bacterial-driven process that depends on the Rab39a GTP- or GDP-binding state. Interestingly, Rab39a participates in the delivery of MVBs and host sphingolipids to maturing chlamydial inclusions, thereby promoting inclusion growth and bacterial development. Taken together, our findings indicate that Rab39a favours chlamydial replication and infectivity. This is the first report showing that a late endocytic Rab GTPase is involved in chlamydial infection development. © 2015. Published by The Company of Biologists Ltd.

Endocytic Uptake, Transport and Macromolecular Interactions of Anionic PAMAM Dendrimers within Lung Tissue.

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Morris, Christopher J; Aljayyoussi, Ghaith; Mansour, Omar; Griffiths, Peter; Gumbleton, Mark

2017-12-01

Polyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers. Anionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat lung (IPRL) model and lung epithelial monolayers. Endocytosis pathways were examined in primary alveolar epithelial cultures by confocal microscopy. Molecular interactions of dendrimers with protein and lipid lung fluid components were studied using small angle neutron scattering (SANS). Dendrimers were absorbed across the intact lung via a passive, size-dependent transport pathway at rates slower than dextrans of similar molecular sizes. SANS investigations of concentration-dependent PAMAM transport in the IPRL confirmed no aggregation of PAMAMs with either albumin or dipalmitoylphosphatidylcholine lung lining fluid components. Distinct endocytic compartments were identified within primary alveolar epithelial cells and their functionality in the rapid uptake of fluorescent dendrimers and model macromolecular probes was confirmed by co-localisation studies. PAMAM dendrimers display favourable lung biocompatibility but modest lung to blood absorption kinetics. These data support the investigation of dendrimer-based carriers for controlled-release drug delivery to the deep lung.

Unique Path Partitions

DEFF Research Database (Denmark)

Bessenrodt, Christine; Olsson, Jørn Børling; Sellers, James A.

2013-01-01

We give a complete classification of the unique path partitions and study congruence properties of the function which enumerates such partitions.......We give a complete classification of the unique path partitions and study congruence properties of the function which enumerates such partitions....

Mapping of the Lassa virus LAMP1 binding site reveals unique determinants not shared by other old world arenaviruses.

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Hadar Israeli

2017-04-01

Full Text Available Cell entry of many enveloped viruses occurs by engagement with cellular receptors, followed by internalization into endocytic compartments and pH-induced membrane fusion. A previously unnoticed step of receptor switching was found to be critical during cell entry of two devastating human pathogens: Ebola and Lassa viruses. Our recent studies revealed the functional role of receptor switching to LAMP1 for triggering membrane fusion by Lassa virus and showed the involvement of conserved histidines in this switching, suggesting that other viruses from this family may also switch to LAMP1. However, when we investigated viruses that are genetically close to Lassa virus, we discovered that they cannot bind LAMP1. A crystal structure of the receptor-binding module from Morogoro virus revealed structural differences that allowed mapping of the LAMP1 binding site to a unique set of Lassa residues not shared by other viruses in its family, illustrating a key difference in the cell-entry mechanism of Lassa virus that may contribute to its pathogenicity.

Exploiting Unique Structural and Functional Properties of Malarial Glycolytic Enzymes for Antimalarial Drug Development

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Asrar Alam

2014-01-01

Full Text Available Metabolic enzymes have been known to carry out a variety of functions besides their normal housekeeping roles known as “moonlighting functions.” These functionalities arise from structural changes induced by posttranslational modifications and/or binding of interacting proteins. Glycolysis is the sole source of energy generation for malaria parasite Plasmodium falciparum, hence a potential pathway for therapeutic intervention. Crystal structures of several P. falciparum glycolytic enzymes have been solved, revealing that they exhibit unique structural differences from the respective host enzymes, which could be exploited for their selective targeting. In addition, these enzymes carry out many parasite-specific functions, which could be of potential interest to control parasite development and transmission. This review focuses on the moonlighting functions of P. falciparum glycolytic enzymes and unique structural differences and functional features of the parasite enzymes, which could be exploited for therapeutic and transmission blocking interventions against malaria.

Exosomes surf on filopodia to enter cells at endocytic hot spots, traffic within endosomes, and are targeted to the ER.

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Heusermann, Wolf; Hean, Justin; Trojer, Dominic; Steib, Emmanuelle; von Bueren, Stefan; Graff-Meyer, Alexandra; Genoud, Christel; Martin, Katrin; Pizzato, Nicolas; Voshol, Johannes; Morrissey, David V; Andaloussi, Samir E L; Wood, Matthew J; Meisner-Kober, Nicole C

2016-04-25

Exosomes are nanovesicles released by virtually all cells, which act as intercellular messengers by transfer of protein, lipid, and RNA cargo. Their quantitative efficiency, routes of cell uptake, and subcellular fate within recipient cells remain elusive. We quantitatively characterize exosome cell uptake, which saturates with dose and time and reaches near 100% transduction efficiency at picomolar concentrations. Highly reminiscent of pathogenic bacteria and viruses, exosomes are recruited as single vesicles to the cell body by surfing on filopodia as well as filopodia grabbing and pulling motions to reach endocytic hot spots at the filopodial base. After internalization, exosomes shuttle within endocytic vesicles to scan the endoplasmic reticulum before being sorted into the lysosome as their final intracellular destination. Our data quantify and explain the efficiency of exosome internalization by recipient cells, establish a new parallel between exosome and virus host cell interaction, and suggest unanticipated routes of subcellular cargo delivery. © 2016 Heusermann et al.

Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex.

NARCIS (Netherlands)

Gentet, L.J.; Kremer, Y.; Taniguchi, H.; Huang, Z.J.; Staiger, J.F.; Petersen, C.C.H.

2012-01-01

Neocortical GABAergic neurons have diverse molecular, structural and electrophysiological features, but the functional correlates of this diversity are largely unknown. We found unique membrane potential dynamics of somatostatin-expressing (SOM) neurons in layer 2/3 of the primary somatosensory

On the stability of unique range sets for meromorphic functions

International Nuclear Information System (INIS)

Ha Huy Khoai; Nguyen Van Khue

2003-03-01

For a set S we construct a complex space Z S such that S is a unique range set for meromorphic functions (URS) if and only if Z S is hyperbolic. A consequence of this result is that the set of URS with n elements (considered as a subset of C n ) is open, and then the small deformations of Yi's and Frank-Reinders' sets are URS. (author)

Age-related changes in the endocytic capacity of rat liver Kupffer and endothelial cells

International Nuclear Information System (INIS)

Brouwer, A.; Barelds, R.J.; Knook, D.L.

1985-01-01

There are many indications that the functional capacity of the reticuloendothelial system (RES) declines with age. The aim of this study was to investigate the cellular basis of age-related changes in the clearance function of the RES. The experiments were focused mainly on Kupffer and endothelial cells of the liver which represent a major part of the RES and are primarily responsible for clearance of colloidal material from the circulation. The clearance capacity of the RES was tested clinically and experimentally by intravenous injection of colloids, such as radiolabeled heat-aggregated colloidal albumin. Age-related changes in the endocytosis of 125 I-labeled colloidal albumin (CA) in rats were determined by clearance and organ distribution of different doses of intravenously injected CA, uptake of CA by Kupffer and endothelial liver cells in vivo as determined after isolation of the cells from injected rats and kinetic studies on CA uptake by Kupffer cells in culture. The results show that, at a low dose, the clearance of CA is primarily determined by liver blood flow. At a higher saturating dose, plasma clearance and uptake by the liver are not significantly decreased with age. Endocytosis by endothelial cells, which accounts for about 60% of that of the whole liver, is also unchanged with age. In contrast, a significant decrease in endocytic capacity was observed for Kupffer cells in vivo. This age-related functional decline was also observed in Kupffer cells which were isolated from rats of different ages and maintained in culture

Autobiographical memory functions of nostalgia in comparison to rumination and counterfactual thinking: similarity and uniqueness.

Science.gov (United States)

Cheung, Wing-Yee; Wildschut, Tim; Sedikides, Constantine

2018-02-01

We compared and contrasted nostalgia with rumination and counterfactual thinking in terms of their autobiographical memory functions. Specifically, we assessed individual differences in nostalgia, rumination, and counterfactual thinking, which we then linked to self-reported functions or uses of autobiographical memory (Self-Regard, Boredom Reduction, Death Preparation, Intimacy Maintenance, Conversation, Teach/Inform, and Bitterness Revival). We tested which memory functions are shared and which are uniquely linked to nostalgia. The commonality among nostalgia, rumination, and counterfactual thinking resides in their shared positive associations with all memory functions: individuals who evinced a stronger propensity towards past-oriented thought (as manifested in nostalgia, rumination, and counterfactual thinking) reported greater overall recruitment of memories in the service of present functioning. The uniqueness of nostalgia resides in its comparatively strong positive associations with Intimacy Maintenance, Teach/Inform, and Self-Regard and weak association with Bitterness Revival. In all, nostalgia possesses a more positive functional signature than do rumination and counterfactual thinking.

Altered TGF-β endocytic trafficking contributes to the increased signaling in Marfan syndrome.

Science.gov (United States)

Siegert, Anna-Maria; Serra-Peinado, Carla; Gutiérrez-Martínez, Enric; Rodríguez-Pascual, Fernando; Fabregat, Isabel; Egea, Gustavo

2018-02-01

The main cardiovascular alteration in Marfan syndrome (MFS) is the formation of aortic aneurysms in which augmented TGF-β signaling is reported. However, the primary role of TGF-β signaling as a molecular link between the genetic mutation of fibrillin-1 and disease onset is controversial. The compartmentalization of TGF-β endocytic trafficking has been shown to determine a signaling response in which clathrin-dependent internalization leads to TGF-β signal propagation, and caveolin-1 (CAV-1) associated internalization leads to signal abrogation. We here studied the contribution of endocytic trafficking compartmentalization to increased TGF-β signaling in vascular smooth muscle cells (VSMC) from MFS patients. We examined molecular components involved in clathrin- (SARA, SMAD2) and caveolin-1- (SMAD7, SMURF2) dependent endocytosis. Marfan VSMC showed higher recruitment of SARA and SMAD2 to membranes and their increased interaction with TGF-β receptor II, as well as higher colocalization of SARA with the early endosome marker EEA1. We assessed TGF-β internalization using a biotinylated ligand (b-TGF-β), which colocalized equally with either EEA1 or CAV-1 in VSMC from Marfan patients and controls. However, in Marfan cells, colocalization of b-TGF-β with SARA and EEA1 was increased and accompanied by decreased colocalization with CAV-1 at EEA1-positive endosomes. Moreover, Marfan VSMC showed higher transcriptional levels and membrane enrichment of RAB5. Our results indicate that increased RAB5-associated SARA localization to early endosomes facilitates its TGF-β receptor binding and phosphorylation of signaling mediator SMAD2 in Marfan VSMC. This is accompanied by a reduction of TGF-β sorting into multifunctional vesicles containing cargo from both internalization pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

Anaesthetics stop diverse plant organ movements, affect endocytic vesicle recycling and ROS homeostasis, and block action potentials in Venus flytraps.

Science.gov (United States)

Yokawa, K; Kagenishi, T; Pavlovic, A; Gall, S; Weiland, M; Mancuso, S; Baluška, F

2017-12-11

Anaesthesia for medical purposes was introduced in the 19th century. However, the physiological mode of anaesthetic drug actions on the nervous system remains unclear. One of the remaining questions is how these different compounds, with no structural similarities and even chemically inert elements such as the noble gas xenon, act as anaesthetic agents inducing loss of consciousness. The main goal here was to determine if anaesthetics affect the same or similar processes in plants as in animals and humans. A single-lens reflex camera was used to follow organ movements in plants before, during and after recovery from exposure to diverse anaesthetics. Confocal microscopy was used to analyse endocytic vesicle trafficking. Electrical signals were recorded using a surface AgCl electrode. Mimosa leaves, pea tendrils, Venus flytraps and sundew traps all lost both their autonomous and touch-induced movements after exposure to anaesthetics. In Venus flytrap, this was shown to be due to the loss of action potentials under diethyl ether anaesthesia. The same concentration of diethyl ether immobilized pea tendrils. Anaesthetics also impeded seed germination and chlorophyll accumulation in cress seedlings. Endocytic vesicle recycling and reactive oxygen species (ROS) balance, as observed in intact Arabidopsis root apex cells, were also affected by all anaesthetics tested. Plants are sensitive to several anaesthetics that have no structural similarities. As in animals and humans, anaesthetics used at appropriate concentrations block action potentials and immobilize organs via effects on action potentials, endocytic vesicle recycling and ROS homeostasis. Plants emerge as ideal model objects to study general questions related to anaesthesia, as well as to serve as a suitable test system for human anaesthesia. © The Authors 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

V-ATPase-dependent luminal acidification is required for endocytic recycling of a yeast cell wall stress sensor, Wsc1p

Energy Technology Data Exchange (ETDEWEB)

Ueno, Kazuma; Saito, Mayu; Nagashima, Makiko; Kojima, Ai; Nishinoaki, Show [Department of Biological Science and Technology, Tokyo University of Science, Niijuku 6-3-1, Katsushika-ku, Tokyo 125-8585 (Japan); Toshima, Junko Y., E-mail: yama_jun@aoni.waseda.jp [Faculty of Science and Engineering, Waseda University, Wakamatsu-cho 2-2, Shinjuku-ku, Tokyo 162-8480 (Japan); Research Center for RNA Science, RIST, Tokyo University of Science, Niijuku 6-3-1, Katsushika-ku, Tokyo 125-8585 (Japan); Toshima, Jiro, E-mail: jtosiscb@rs.noda.tus.ac.jp [Department of Biological Science and Technology, Tokyo University of Science, Niijuku 6-3-1, Katsushika-ku, Tokyo 125-8585 (Japan); Research Center for RNA Science, RIST, Tokyo University of Science, Niijuku 6-3-1, Katsushika-ku, Tokyo 125-8585 (Japan)

2014-01-10

Highlights: •A targeted genome screen identified 5 gene groups affecting Wsc1p recycling. •V-ATPase-dependent luminal acidification is required for Wsc1p recycling. •Activity of V-ATPase might be required for cargo recognition by the retromer complex. -- Abstract: Wsc1p is a major cell wall sensor protein localized at the polarized cell surface. The localization of Wsc1p is maintained by endocytosis and recycling from endosomes back to the cell surface, but changes to the vacuole when cells are subjected to heat stress. Exploiting this unique property of Wsc1p, we screened for yeast single-gene deletion mutants exhibiting defects in Wsc1p trafficking. By expressing 3GFP-tagged Wsc1p in mutants with deleted genes whose function is related to intracellular trafficking, we identified 5 gene groups affecting Wsc1p trafficking, impaired respectively in endocytic internalization, multivesicular body sorting, the GARP complex, endosomal maturation/vacuolar fusion, and V-ATPase. Interestingly, deletion of the VPH1 gene, encoding the V{sub o} subunit of vacuolar-type H{sup +}-ATPase (V-ATPase), led to mis-localization of Wsc1p from the plasma membrane to the vacuole. In addition, disruption of other V-ATPase subunits (vma mutants) also caused defects of Wsc1p trafficking and vacuolar acidification similar to those seen in the vph1Δ mutant. Moreover, we found that deletion of the VPS26 gene, encoding a subunit of the retromer complex, also caused a defect in Wsc1p recycling and mis-localization of Wsc1p to the vacuole. These findings clarified the previously unidentified Wsc1p recycling pathway and requirement of V-ATPase-dependent luminal acidification for Wsc1p recycling.

V-ATPase-dependent luminal acidification is required for endocytic recycling of a yeast cell wall stress sensor, Wsc1p

International Nuclear Information System (INIS)

Ueno, Kazuma; Saito, Mayu; Nagashima, Makiko; Kojima, Ai; Nishinoaki, Show; Toshima, Junko Y.; Toshima, Jiro

2014-01-01

Highlights: •A targeted genome screen identified 5 gene groups affecting Wsc1p recycling. •V-ATPase-dependent luminal acidification is required for Wsc1p recycling. •Activity of V-ATPase might be required for cargo recognition by the retromer complex. -- Abstract: Wsc1p is a major cell wall sensor protein localized at the polarized cell surface. The localization of Wsc1p is maintained by endocytosis and recycling from endosomes back to the cell surface, but changes to the vacuole when cells are subjected to heat stress. Exploiting this unique property of Wsc1p, we screened for yeast single-gene deletion mutants exhibiting defects in Wsc1p trafficking. By expressing 3GFP-tagged Wsc1p in mutants with deleted genes whose function is related to intracellular trafficking, we identified 5 gene groups affecting Wsc1p trafficking, impaired respectively in endocytic internalization, multivesicular body sorting, the GARP complex, endosomal maturation/vacuolar fusion, and V-ATPase. Interestingly, deletion of the VPH1 gene, encoding the V o subunit of vacuolar-type H + -ATPase (V-ATPase), led to mis-localization of Wsc1p from the plasma membrane to the vacuole. In addition, disruption of other V-ATPase subunits (vma mutants) also caused defects of Wsc1p trafficking and vacuolar acidification similar to those seen in the vph1Δ mutant. Moreover, we found that deletion of the VPS26 gene, encoding a subunit of the retromer complex, also caused a defect in Wsc1p recycling and mis-localization of Wsc1p to the vacuole. These findings clarified the previously unidentified Wsc1p recycling pathway and requirement of V-ATPase-dependent luminal acidification for Wsc1p recycling

Comparative fecal metagenomics unveils unique functional capacity of the swine gut

Directory of Open Access Journals (Sweden)

Martinson John

2011-05-01

Full Text Available Abstract Background Uncovering the taxonomic composition and functional capacity within the swine gut microbial consortia is of great importance to animal physiology and health as well as to food and water safety due to the presence of human pathogens in pig feces. Nonetheless, limited information on the functional diversity of the swine gut microbiome is available. Results Analysis of 637, 722 pyrosequencing reads (130 megabases generated from Yorkshire pig fecal DNA extracts was performed to help better understand the microbial diversity and largely unknown functional capacity of the swine gut microbiome. Swine fecal metagenomic sequences were annotated using both MG-RAST and JGI IMG/M-ER pipelines. Taxonomic analysis of metagenomic reads indicated that swine fecal microbiomes were dominated by Firmicutes and Bacteroidetes phyla. At a finer phylogenetic resolution, Prevotella spp. dominated the swine fecal metagenome, while some genes associated with Treponema and Anareovibrio species were found to be exclusively within the pig fecal metagenomic sequences analyzed. Functional analysis revealed that carbohydrate metabolism was the most abundant SEED subsystem, representing 13% of the swine metagenome. Genes associated with stress, virulence, cell wall and cell capsule were also abundant. Virulence factors associated with antibiotic resistance genes with highest sequence homology to genes in Bacteroidetes, Clostridia, and Methanosarcina were numerous within the gene families unique to the swine fecal metagenomes. Other abundant proteins unique to the distal swine gut shared high sequence homology to putative carbohydrate membrane transporters. Conclusions The results from this metagenomic survey demonstrated the presence of genes associated with resistance to antibiotics and carbohydrate metabolism suggesting that the swine gut microbiome may be shaped by husbandry practices.

Diverse functions of myosin VI elucidated by an isoform-specific α-helix domain.

Science.gov (United States)

Wollscheid, Hans-Peter; Biancospino, Matteo; He, Fahu; Magistrati, Elisa; Molteni, Erika; Lupia, Michela; Soffientini, Paolo; Rottner, Klemens; Cavallaro, Ugo; Pozzoli, Uberto; Mapelli, Marina; Walters, Kylie J; Polo, Simona

2016-04-01

Myosin VI functions in endocytosis and cell motility. Alternative splicing of myosin VI mRNA generates two distinct isoform types, myosin VI(short) and myosin VI(long), which differ in the C-terminal region. Their physiological and pathological roles remain unknown. Here we identified an isoform-specific regulatory helix, named the α2-linker, that defines specific conformations and hence determines the target selectivity of human myosin VI. The presence of the α2-linker structurally defines a new clathrin-binding domain that is unique to myosin VI(long) and masks the known RRL interaction motif. This finding is relevant to ovarian cancer, in which alternative myosin VI splicing is aberrantly regulated, and exon skipping dictates cell addiction to myosin VI(short) in tumor-cell migration. The RRL interactor optineurin contributes to this process by selectively binding myosin VI(short). Thus, the α2-linker acts like a molecular switch that assigns myosin VI to distinct endocytic (myosin VI(long)) or migratory (myosin VI(short)) functional roles.

Multiple polysaccharide-drug complex-loaded liposomes: A unique strategy in drug loading and cancer targeting.

Science.gov (United States)

Ruttala, Hima Bindu; Ramasamy, Thiruganesh; Gupta, Biki; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2017-10-01

In the present study, a unique strategy was developed to develop nanocarriers containing multiple therapeutics with controlled release characteristics. In this study, we demonstrated the synthesis of dextran sulfate-doxorubicin (DS-DOX) and alginate-cisplatin (AL-CIS) polymer-drug complexes to produce a transferrin ligand-conjugated liposome. The targeted nanoparticles (TL-DDAC) were nano-sized and spherical. The targeted liposome exhibited a specific receptor-mediated endocytic uptake in cancer cells. The enhanced cellular uptake of TL-DDAC resulted in a significantly better anticancer effect in resistant and sensitive breast cancer cells compared to that of the free drugs. Specifically, DOX and CIS at a molar ratio of 1:1 exhibited better therapeutic performance compared to that of other combinations. The combination of an anthracycline-based topoisomerase II inhibitor (DOX) and a platinum compound (CIS) resulted in significantly higher cell apoptosis (early and late) in both types of cancer cells. In conclusion, treatment with DS-DOX and AL-CIS based combination liposomes modified with transferrin (TL-DDAC) was an effective cancer treatment strategy. Further investigation in clinically relevant animal models is warranted to prove the therapeutic efficacy of this unique strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stem-cell-specific endocytic degradation defects lead to intestinal dysplasia in Drosophila

Directory of Open Access Journals (Sweden)

Péter Nagy

2016-05-01

Full Text Available UV radiation resistance-associated gene (UVRAG is a tumor suppressor involved in autophagy, endocytosis and DNA damage repair, but how its loss contributes to colorectal cancer is poorly understood. Here, we show that UVRAG deficiency in Drosophila intestinal stem cells leads to uncontrolled proliferation and impaired differentiation without preventing autophagy. As a result, affected animals suffer from gut dysfunction and short lifespan. Dysplasia upon loss of UVRAG is characterized by the accumulation of endocytosed ligands and sustained activation of STAT and JNK signaling, and attenuation of these pathways suppresses stem cell hyperproliferation. Importantly, the inhibition of early (dynamin-dependent or late (Rab7-dependent steps of endocytosis in intestinal stem cells also induces hyperproliferation and dysplasia. Our data raise the possibility that endocytic, but not autophagic, defects contribute to UVRAG-deficient colorectal cancer development in humans.

Megalin and cubilin are endocytic receptors involved in renal clearance of hemoglobin

DEFF Research Database (Denmark)

Gburek, Jakub; Verroust, Pierre J; Willnow, Thomas E

2002-01-01

-Sepharose affinity chromatography of solubilized renal brush-border membranes. Apparent dissociation constants of 1.7 microM for megalin and 4.1 microM for cubilin were determined by surface plasmon resonance analysis. The binding was calcium dependent in both cases. Uptake of fluorescence-labeled hemoglobin by BN......The kidney is the main site of hemoglobin clearance and degradation in conditions of severe hemolysis. Herein it is reported that megalin and cubilin, two epithelial endocytic receptors, mediate the uptake of hemoglobin in renal proximal tubules. Both receptors were purified by use of hemoglobin...... not affect the uptake. By use of immunohistochemistry, it was demonstrated that uptake of hemoglobin in proximal tubules of rat, mouse, and dog kidneys occurs under physiologic conditions. Studies on normal and megalin knockout mouse kidney sections showed that megalin is responsible for physiologic...

BAD-LAMP defines a subset of early endocytic organelles in subpopulations of cortical projection neurons.

Science.gov (United States)

David, Alexandre; Tiveron, Marie-Catherine; Defays, Axel; Beclin, Christophe; Camosseto, Voahirana; Gatti, Evelina; Cremer, Harold; Pierre, Philippe

2007-01-15

The brain-associated LAMP-like molecule (BAD-LAMP) is a new member of the family of lysosome associated membrane proteins (LAMPs). In contrast to other LAMPs, which show a widespread expression, BAD-LAMP expression in mice is confined to the postnatal brain and therein to neuronal subpopulations in layers II/III and V of the neocortex. Onset of expression strictly parallels cortical synaptogenesis. In cortical neurons, the protein is found in defined clustered vesicles, which accumulate along neurites where it localizes with phosphorylated epitopes of neurofilament H. In primary neurons, BAD-LAMP is endocytosed, but is not found in classical lysosomal/endosomal compartments. Modification of BAD-LAMP by addition of GFP revealed a cryptic lysosomal retention motif, suggesting that the cytoplasmic tail of BAD-LAMP is actively interacting with, or modified by, molecules that promote its sorting away from lysosomes. Analysis of BAD-LAMP endocytosis in transfected HeLa cells provided evidence that the protein recycles to the plasma membrane through a dynamin/AP2-dependent mechanism. Thus, BAD-LAMP is an unconventional LAMP-like molecule and defines a new endocytic compartment in specific subtypes of cortical projection neurons. The striking correlation between the appearance of BAD-LAMP and cortical synatogenesis points towards a physiological role of this vesicular determinant for neuronal function.

On the existence and uniqueness of minima and maxima on spheres of the integral functional of the calculus of variations

OpenAIRE

Ricceri, Biagio

2005-01-01

We deal with the integral functional of the calculus of variations assuming that the gradient of the integrand is Lipschitzian. We then prove that if this gradient does not vanish at zero, then the functional has a unique minimum and a unique maximum on each sphere, centered at zero, with radius small enough.

On the existence and uniqueness of minima and maxima on spheres of the integral functional of the calculus of variations

Science.gov (United States)

Ricceri, Biagio

2006-12-01

Given a bounded domain [Omega][subset of]Rn, we prove that if is a C1 function whose gradient is Lipschitzian in Rn+1 and non-zero at 0, then, for each r>0 small enough, the restriction of the integral functional to the sphere has a unique global minimum and a unique global maximum.

Value Distribution and Uniqueness Results of Zero-Order Meromorphic Functions to Their q-Shift

Directory of Open Access Journals (Sweden)

Haiwa Guan

2012-01-01

Full Text Available We investigate value distribution and uniqueness problems of meromorphic functions with their q-shift. We obtain that if f is a transcendental meromorphic (or entire function of zero order, and Q(z is a polynomial, then afn(qz+f(z−Q(z has infinitely many zeros, where q∈ℂ∖{0}, a is nonzero constant, and n≥5 (or n≥3. We also obtain that zero-order meromorphic function share is three distinct values IM with its q-difference polynomial P(f, and if limsup r→∞(N(r,f/T(r,f<1, then f≡P(f.

Uniqueness and non-uniqueness of semigroups generated by singular diffusion operators

CERN Document Server

Eberle, Andreas

1999-01-01

This book addresses both probabilists working on diffusion processes and analysts interested in linear parabolic partial differential equations with singular coefficients. The central question discussed is whether a given diffusion operator, i.e., a second order linear differential operator without zeroth order term, which is a priori defined on test functions over some (finite or infinite dimensional) state space only, uniquely determines a strongly continuous semigroup on a corresponding weighted Lp space. Particular emphasis is placed on phenomena causing non-uniqueness, as well as on the relation between different notions of uniqueness appearing in analytic and probabilistic contexts.

Cone photoreceptor sensitivities and unique hue chromatic responses: correlation and causation imply the physiological basis of unique hues.

Science.gov (United States)

Pridmore, Ralph W

2013-01-01

This paper relates major functions at the start and end of the color vision process. The process starts with three cone photoreceptors transducing light into electrical responses. Cone sensitivities were once expected to be Red Green Blue color matching functions (to mix colors) but microspectrometry proved otherwise: they instead peak in yellowish, greenish, and blueish hues. These physiological functions are an enigma, unmatched with any set of psychophysical (behavioral) functions. The end-result of the visual process is color sensation, whose essential percepts are unique (or pure) hues red, yellow, green, blue. Unique hues cannot be described by other hues, but can describe all other hues, e.g., that hue is reddish-blue. They are carried by four opponent chromatic response curves but the literature does not specify whether each curve represents a range of hues or only one hue (a unique) over its wavelength range. Here the latter is demonstrated, confirming that opponent chromatic responses define, and may be termed, unique hue chromatic responses. These psychophysical functions also are an enigma, unmatched with any physiological functions or basis. Here both enigmas are solved by demonstrating the three cone sensitivity curves and the three spectral chromatic response curves are almost identical sets (Pearson correlation coefficients r from 0.95-1.0) in peak wavelengths, curve shapes, math functions, and curve crossover wavelengths, though previously unrecognized due to presentation of curves in different formats, e.g., log, linear. (Red chromatic response curve is largely nonspectral and thus derives from two cones.) Close correlation combined with deterministic causation implies cones are the physiological basis of unique hues. This match of three physiological and three psychophysical functions is unique in color vision.

Unique determination of the effective potential in terms of renormalization group functions

International Nuclear Information System (INIS)

Chishtie, F. A.; Hanif, T.; McKeon, D. G. C.; Steele, T. G.

2008-01-01

The perturbative effective potential V in the massless λφ 4 model with a global O(N) symmetry is uniquely determined to all orders by the renormalization group functions alone when the Coleman-Weinberg renormalization condition (d 4 V/dφ 4 )| φ=μ =λ is used, where μ represents the renormalization scale. Systematic methods are developed to express the n-loop effective potential in the Coleman-Weinberg scheme in terms of the known n-loop minimal-subtraction (MS) renormalization group functions. Moreover, it also proves possible to sum the leading- and subsequent-to-leading-logarithm contributions to V. An essential element of this analysis is a conversion of the renormalization group functions in the Coleman-Weinberg scheme to the renormalization group functions in the MS scheme. As an example, the explicit five-loop effective potential is obtained from the known five-loop MS renormalization group functions and we explicitly sum the leading-logarithm, next-to-leading-logarithm, and further subleading-logarithm contributions to V. Extensions of these results to massless scalar QED are also presented. Because massless scalar QED has two couplings, conversion of the renormalization group functions from the MS scheme to the Coleman-Weinberg scheme requires the use of multiscale renormalization group methods.

Cone photoreceptor sensitivities and unique hue chromatic responses: correlation and causation imply the physiological basis of unique hues.

Directory of Open Access Journals (Sweden)

Ralph W Pridmore

Full Text Available This paper relates major functions at the start and end of the color vision process. The process starts with three cone photoreceptors transducing light into electrical responses. Cone sensitivities were once expected to be Red Green Blue color matching functions (to mix colors but microspectrometry proved otherwise: they instead peak in yellowish, greenish, and blueish hues. These physiological functions are an enigma, unmatched with any set of psychophysical (behavioral functions. The end-result of the visual process is color sensation, whose essential percepts are unique (or pure hues red, yellow, green, blue. Unique hues cannot be described by other hues, but can describe all other hues, e.g., that hue is reddish-blue. They are carried by four opponent chromatic response curves but the literature does not specify whether each curve represents a range of hues or only one hue (a unique over its wavelength range. Here the latter is demonstrated, confirming that opponent chromatic responses define, and may be termed, unique hue chromatic responses. These psychophysical functions also are an enigma, unmatched with any physiological functions or basis. Here both enigmas are solved by demonstrating the three cone sensitivity curves and the three spectral chromatic response curves are almost identical sets (Pearson correlation coefficients r from 0.95-1.0 in peak wavelengths, curve shapes, math functions, and curve crossover wavelengths, though previously unrecognized due to presentation of curves in different formats, e.g., log, linear. (Red chromatic response curve is largely nonspectral and thus derives from two cones. Close correlation combined with deterministic causation implies cones are the physiological basis of unique hues. This match of three physiological and three psychophysical functions is unique in color vision.

Mechanisms of EHD/RME-1 Protein Function in Endocytic Transport

Science.gov (United States)

Grant, Barth D.; Caplan, Steve

2009-01-01

The evolutionarily conserved Eps15 homology domain (EHD)/receptor-mediated endocytosis (RME)-1 family of C-terminal EH domain proteins has recently come under intense scrutiny because of its importance in intracellular membrane transport, especially with regard to the recycling of receptors from endosomes to the plasma membrane. Recent studies have shed new light on the mode by which these adenosine triphosphatases function on endosomal membranes in mammals and Caenorhabditis elegans. This review highlights our current understanding of the physiological roles of these proteins in vivo, discussing conserved features as well as emerging functional differences between individual mammalian paralogs. In addition, these findings are discussed in light of the identification of novel EHD/RME-1 protein and lipid interactions and new structural data for proteins in this family, indicating intriguing similarities to the Dynamin superfamily of large guanosine triphosphatases. PMID:18801062

The unique functioning of a pre-Columbian Amazonian floodplain fishery.

Science.gov (United States)

Blatrix, Rumsaïs; Roux, Bruno; Béarez, Philippe; Prestes-Carneiro, Gabriela; Amaya, Marcelo; Aramayo, Jose Luis; Rodrigues, Leonor; Lombardo, Umberto; Iriarte, Jose; de Souza, Jonas Gregorio; Robinson, Mark; Bernard, Cyril; Pouilly, Marc; Durécu, Mélisse; Huchzermeyer, Carl F; Kalebe, Mashuta; Ovando, Alex; McKey, Doyle

2018-04-16

Archaeology provides few examples of large-scale fisheries at the frontier between catching and farming of fish. We analysed the spatial organization of earthen embankments to infer the functioning of a landscape-level pre-Columbian Amazonian fishery that was based on capture of out-migrating fish after reproduction in seasonal floodplains. Long earthen weirs cross floodplains. We showed that weirs bear successive V-shaped features (termed 'Vs' for the sake of brevity) pointing downstream for outflowing water and that ponds are associated with Vs, the V often forming the pond's downstream wall. How Vs channelled fish into ponds cannot be explained simply by hydraulics, because Vs surprisingly lack fishways, where, in other weirs, traps capture fish borne by current flowing through these gaps. We suggest that when water was still high enough to flow over the weir, out-migrating bottom-hugging fish followed current downstream into Vs. Finding deeper, slower-moving water, they remained. Receding water further concentrated fish in ponds. The pond served as the trap, and this function shaped pond design. Weir-fishing and pond-fishing are both practiced in African floodplains today. In combining the two, this pre-Columbian system appears unique in the world.

Chemical Shift Assignments of the C-terminal Eps15 Homology Domain-3 EH Domain*

Science.gov (United States)

Caplan, Steve; Sorgen, Paul L.

2013-01-01

The C-terminal Eps15 homology (EH) domain 3 (EHD3) belongs to a eukaryotic family of endocytic regulatory proteins and is involved in the recycling of various receptors from the early endosome to the endocytic recycling compartment or in retrograde transport from the endosomes to the Golgi. EH domains are highly conserved in the EHD family and function as protein-protein interaction units that bind to Asn-Pro-Phe (NPF) motif-containing proteins. The EH domain of EHD1 was the first C-terminal EH domain from the EHD family to be solved by NMR. The differences observed between this domain and proteins with N-terminal EH domains helped describe a mechanism for the differential binding of NPF-containing proteins. Here, structural studies were expanded to include the EHD3 EH domain. While the EHD1 and EHD3 EH domains are highly homologous, they have different protein partners. A comparison of these structures will help determine the selectivity in protein binding between the EHD family members and lead to a better understanding of their unique roles in endocytic regulation. PMID:23754701

Rationally Engineering Phototherapy Modules of Eosin-Conjugated Responsive Polymeric Nanocarriers via Intracellular Endocytic pH Gradients.

Science.gov (United States)

Liu, Guhuan; Hu, Jinming; Zhang, Guoying; Liu, Shiyong

2015-07-15

Spatiotemporal switching of respective phototherapy modes at the cellular level with minimum side effects and high therapeutic efficacy is a major challenge for cancer phototherapy. Herein we demonstrate how to address this issue by employing photosensitizer-conjugated pH-responsive block copolymers in combination with intracellular endocytic pH gradients. At neutral pH corresponding to extracellular and cytosol milieu, the copolymers self-assemble into micelles with prominently quenched fluorescence emission and low (1)O2 generation capability, favoring a highly efficient photothermal module. Under mildly acidic pH associated with endolysosomes, protonation-triggered micelle-to-unimer transition results in recovered emission and enhanced photodynamic (1)O2 efficiency, which synergistically actuates release of encapsulated drugs, endosomal escape, and photochemical internalization processes.

Intravital Microscopy Reveals Differences in the Kinetics of Endocytic Pathways between Cell Cultures and Live Animals

Directory of Open Access Journals (Sweden)

Roberto Weigert

2012-11-01

Full Text Available Intravital microscopy has enabled imaging of the dynamics of subcellular structures in live animals, thus opening the door to investigating membrane trafficking under physiological conditions. Here, we sought to determine whether the architecture and the environment of a fully developed tissue influences the dynamics of endocytic processes. To this aim, we imaged endocytosis in the stromal cells of rat salivary glands both in situ and after they were isolated and cultured on a solid surface. We found that the internalization of transferrin and dextran, two molecules that traffic via distinct mechanisms, is substantially altered in cultured cells, supporting the idea that the three dimensional organization of the tissue and the cues generated by the surrounding environment strongly affect membrane trafficking events.

Functional profiles reveal unique ecological roles of various biological soil crust organisms

Science.gov (United States)

Bowker, M.A.; Mau, R.L.; Maestre, F.T.; Escolar, C.; Castillo-Monroy, A. P.

2011-01-01

1. At the heart of the body of research on biodiversity effects on ecosystem function is the debate over whether different species tend to be functionally singular or redundant. When we consider ecosystem multi-function, the provision of multiple ecosystem functions simultaneously, we may find that seemingly redundant species may in fact play unique roles in ecosystems. 2. Over the last few decades, the significance of biological soil crusts (BSCs) as ecological boundaries and ecosystem engineers, and their multi-functional nature, has become increasingly well documented. We compiled 'functional profiles' of the organisms in this understudied community, to determine whether functional singularity emerges when multiple ecosystem functions are considered. 3. In two data sets, one representing multiple sites around the semi-arid regions of Spain (regional scale), and another from a single site in central Spain (local scale), we examined correlations between the abundance or frequency of BSC species in a community, and multiple surrogates of ecosystem functioning. There was a wide array of apparent effects of species on specific functions. 4. Notably, in gypsiferous soils and at regional scale, we found that indicators of carbon (C) and phosphorus cycling were apparently suppressed and promoted by the lichens Diploschistes diacapsis and Squamarina lentigera, respectively. The moss Pleurochaete squarrosa appears to promote C cycling in calcareous soils at this spatial scale. At the local scale in gypsiferous soils, D. diacapsis positively correlated with carbon cycling, but negatively with nitrogen cycling, whereas numerous lichens exhibited the opposite profile. 5. We found a high degree of functional singularity, i.e. that species were highly individualistic in their effects on multiple functions. Many functional attributes were not easily predictable from existing functional grouping systems based primarily on morphology. 6. Our results suggest that maintaining

Coexistence of uniquely ergodic subsystems of interval mapping

International Nuclear Information System (INIS)

Ye Xiangdong.

1991-10-01

The purpose of this paper is to show that uniquely ergodic subsystems of interval mapping also coexist in the same way as minimal sets do. To do this we give some notations in section 2. In section 3 we define D-function of a uniquely ergodic system and show its basic properties. We prove the coexistence of uniquely ergodic subsystems of interval mapping in section 4. Lastly we give the examples of uniquely ergodic systems with given D-functions in section 5. 27 refs

Existence, uniqueness, and stability of stochastic neutral functional differential equations of Sobolev-type

Energy Technology Data Exchange (ETDEWEB)

Yang, Xuetao; Zhu, Quanxin, E-mail: zqx22@126.com [School of Mathematical Sciences and Institute of Mathematics, Nanjing Normal University, Nanjing 210023, Jiangsu (China)

2015-12-15

In this paper, we are mainly concerned with a class of stochastic neutral functional differential equations of Sobolev-type with Poisson jumps. Under two different sets of conditions, we establish the existence of the mild solution by applying the Leray-Schauder alternative theory and the Sadakovskii’s fixed point theorem, respectively. Furthermore, we use the Bihari’s inequality to prove the Osgood type uniqueness. Also, the mean square exponential stability is investigated by applying the Gronwall inequality. Finally, two examples are given to illustrate the theory results.

Soyasaponin Bh, a Triterpene Saponin Containing a Unique Hemiacetal-Functional Five-Membered Ring from Glycine max (Soybeans)

Science.gov (United States)

Soybeans (Glycine max L. Merill) and soy-based food products are major dietary sources of saponins. An oleanane triterpenoid saponin, soyasaponin Bh (1) containing a unique five-membered ring with a hemiacetal functionality together with seven known saponins were isolated from soybeans. Their struct...

Snapin-regulated late endosomal transport is critical for efficient autophagy-lysosomal function in neurons.

Science.gov (United States)

Cai, Qian; Lu, Li; Tian, Jin-Hua; Zhu, Yi-Bing; Qiao, Haifa; Sheng, Zu-Hang

2010-10-06

Neuron maintenance and survival require late endocytic transport from distal processes to the soma where lysosomes are predominantly localized. Here, we report a role for Snapin in attaching dynein to late endosomes through its intermediate chain (DIC). snapin(-/-) neurons exhibit aberrant accumulation of immature lysosomes, clustering and impaired retrograde transport of late endosomes along processes, reduced lysosomal proteolysis due to impaired delivery of internalized proteins and hydrolase precursors from late endosomes to lysosomes, and impaired clearance of autolysosomes, combined with reduced neuron viability and neurodegeneration. The phenotypes are rescued by expressing the snapin transgene, but not the DIC-binding-defective Snapin-L99K mutant. Snapin overexpression in wild-type neurons enhances late endocytic transport and lysosomal function, whereas expressing the mutant defective in Snapin-DIC coupling shows a dominant-negative effect. Altogether, our study highlights new mechanistic insights into how Snapin-DIC coordinates retrograde transport and late endosomal-lysosomal trafficking critical for autophagy-lysosomal function, and thus neuronal homeostasis. Copyright © 2010 Elsevier Inc. All rights reserved.

Endocytic pathways involved in PLGA nanoparticle uptake by grapevine cells and role of cell wall and membrane in size selection.

Science.gov (United States)

Palocci, Cleofe; Valletta, Alessio; Chronopoulou, Laura; Donati, Livia; Bramosanti, Marco; Brasili, Elisa; Baldan, Barbara; Pasqua, Gabriella

2017-12-01

PLGA NPs' cell uptake involves different endocytic pathways. Clathrin-independent endocytosis is the main internalization route. The cell wall plays a more prominent role than the plasma membrane in NPs' size selection. In the last years, many studies on absorption and cell uptake of nanoparticles by plants have been conducted, but the understanding of the internalization mechanisms is still largely unknown. In this study, polydispersed and monodispersed poly(lactic-co-glycolic) acid nanoparticles (PLGA NPs) were synthesized, and a strategy combining the use of transmission electron microscopy (TEM), confocal analysis, fluorescently labeled PLGA NPs, a probe for endocytic vesicles (FM4-64), and endocytosis inhibitors (i.e., wortmannin, ikarugamycin, and salicylic acid) was employed to shed light on PLGA NP cell uptake in grapevine cultured cells and to assess the role of the cell wall and plasma membrane in size selection of PLGA NPs. The ability of PLGA NPs to cross the cell wall and membrane was confirmed by TEM and fluorescence microscopy. A strong adhesion of PLGA NPs to the outer side of the cell wall was observed, presumably due to electrostatic interactions. Confocal microscopy and treatment with endocytosis inhibitors suggested the involvement of both clathrin-dependent and clathrin-independent endocytosis in cell uptake of PLGA NPs and the latter appeared to be the main internalization pathway. Experiments on grapevine protoplasts revealed that the cell wall plays a more prominent role than the plasma membrane in size selection of PLGA NPs. While the cell wall prevents the uptake of PLGA NPs with diameters over 50 nm, the plasma membrane can be crossed by PLGA NPs with a diameter of 500-600 nm.

Is Life Unique?

Science.gov (United States)

Abel, David L.

2011-01-01

Is life physicochemically unique? No. Is life unique? Yes. Life manifests innumerable formalisms that cannot be generated or explained by physicodynamics alone. Life pursues thousands of biofunctional goals, not the least of which is staying alive. Neither physicodynamics, nor evolution, pursue goals. Life is largely directed by linear digital programming and by the Prescriptive Information (PI) instantiated particularly into physicodynamically indeterminate nucleotide sequencing. Epigenomic controls only compound the sophistication of these formalisms. Life employs representationalism through the use of symbol systems. Life manifests autonomy, homeostasis far from equilibrium in the harshest of environments, positive and negative feedback mechanisms, prevention and correction of its own errors, and organization of its components into Sustained Functional Systems (SFS). Chance and necessity—heat agitation and the cause-and-effect determinism of nature’s orderliness—cannot spawn formalisms such as mathematics, language, symbol systems, coding, decoding, logic, organization (not to be confused with mere self-ordering), integration of circuits, computational success, and the pursuit of functionality. All of these characteristics of life are formal, not physical. PMID:25382119

Intracisternal granules in the adipokinetic cells of locusts are not degraded and apparently function as supplementary stores of secretory material.

Science.gov (United States)

Harthoorn, L F; Diederen, J H; Oudejans, R C; Verstegen, M M; Vullings, H G; Van der Horst, D J

2000-01-01

The intracisternal granules in locust adipokinetic cells appear to represent accumulations of secretory material within cisternae of the rough endoplasmic reticulum. An important question is whether these granules are destined for degradation or represent stores of (pro)hormones. Two strategies were used to answer this question. First, cytochemistry was applied to elucidate the properties of intracisternal granules. The endocytic tracers horseradish peroxidase and wheat-germ agglutinin-conjugated horseradish peroxidase were used to facilitate the identification of endocytic, autophagic, and lysosomal organelles, which may be involved in the degradation of intracisternal granules. No intracisternal granules could be found within autophagosomes, and granules fused with endocytic and lysosomal organelles were not observed, nor could tracer be found within the granules. The lysosomal enzyme acid phosphatase was absent from the granules. Second, biochemical analysis of the content of intracisternal granules revealed that these granules contain prohormones as well as hormones. Prohormones were present in relatively higher amounts compared with ordinary secretory granules. Since the intracisternal granules in locust adipokinetic cells are not degraded and contain intact (pro)hormones it is concluded that they function as supplementary stores of secretory material.

Clathrin-independent endocytosis: mechanisms and function

DEFF Research Database (Denmark)

Sandvig, Kirsten; Pust, Sascha; Skotland, Tore

2011-01-01

It is now about 20 years since we first wrote reviews about clathrin-independent endocytosis. The challenge at the time was to convince the reader about its existence. Then the suggestion came up that caveolae might be responsible for the uptake. However, clearly this could not be the case since ...... having several functions of their own. This article aims at providing a brief update on the importance of clathrin-independent endocytic mechanisms, how the processes are regulated differentially, for instance on the poles of polarized cells, and the challenges in studying them....

Unique proline-benzoquinone pigment from the colored nectar of "bird's Coca cola tree" functions in bird attractions.

Science.gov (United States)

Luo, Shi-Hong; Liu, Yan; Hua, Juan; Niu, Xue-Mei; Jing, Shu-Xi; Zhao, Xu; Schneider, Bernd; Gershenzon, Jonathan; Li, Sheng-Hong

2012-08-17

The major pigment responsible for the dark brown nectar of the "bird's Coca cola tree", Leucosceptrum canum (Labiatae), was isolated and identified as a unique symmetric proline-quinone conjugate, 2,5-di-(N-(-)-prolyl)-para-benzoquinone (DPBQ). Behavioral experiments with both isolated and synthetic authentic samples indicated that DPBQ functions mainly as a color attractant to bird pollinators.

The unique rht-MOF platform, ideal for pinpointing the functionalization and CO 2 adsorption relationship

KAUST Repository

Luebke, Ryan

2012-01-01

The uniqueness of the rht-MOF platform, based on the singular (3,24)-connected net, allows for the facile design and synthesis of functionalized materials for desired applications. Here we designed a nitrogen-rich trefoil hexacarboxylate (trigonal tri-isophthalate) ligand, which serves to act as the trigonal molecular building block while concurrently coding the formation of the targeted truncated cuboctahedral supermolecular building block (in situ), and enhancing the CO 2 uptake in the resultant rht-MOF. © 2012 The Royal Society of Chemistry.

Visualization of the endocytic pathway in the filamentous fungus Aspergillus oryzae using an EGFP-fused plasma membrane protein

International Nuclear Information System (INIS)

Higuchi, Yujiro; Nakahama, Tomoyuki; Shoji, Jun-ya; Arioka, Manabu; Kitamoto, Katsuhiko

2006-01-01

Endocytosis is an important process for cellular activities. However, in filamentous fungi, the existence of endocytosis has been so far elusive. In this study, we used AoUapC-EGFP, the fusion protein of a putative uric acid-xanthine permease with enhanced green fluorescent protein (EGFP) in Aspergillus oryzae, to examine whether the endocytic process occurs or not. Upon the addition of ammonium into the medium the fusion protein was internalized from the plasma membrane. The internalization of AoUapC-EGFP was completely blocked by sodium azide, cold, and cytochalasin A treatments, suggesting that the internalization possesses the general features of endocytosis. These results demonstrate the occurrence of endocytosis in filamentous fungi. Moreover, we discovered that the endosomal compartments appeared upon the induction of endocytosis and moved in a microtubule-dependent manner

On convergence of differential evolution over a class of continuous functions with unique global optimum.

Science.gov (United States)

Ghosh, Sayan; Das, Swagatam; Vasilakos, Athanasios V; Suresh, Kaushik

2012-02-01

Differential evolution (DE) is arguably one of the most powerful stochastic real-parameter optimization algorithms of current interest. Since its inception in the mid 1990s, DE has been finding many successful applications in real-world optimization problems from diverse domains of science and engineering. This paper takes a first significant step toward the convergence analysis of a canonical DE (DE/rand/1/bin) algorithm. It first deduces a time-recursive relationship for the probability density function (PDF) of the trial solutions, taking into consideration the DE-type mutation, crossover, and selection mechanisms. Then, by applying the concepts of Lyapunov stability theorems, it shows that as time approaches infinity, the PDF of the trial solutions concentrates narrowly around the global optimum of the objective function, assuming the shape of a Dirac delta distribution. Asymptotic convergence behavior of the population PDF is established by constructing a Lyapunov functional based on the PDF and showing that it monotonically decreases with time. The analysis is applicable to a class of continuous and real-valued objective functions that possesses a unique global optimum (but may have multiple local optima). Theoretical results have been substantiated with relevant computer simulations.

CD163-L1 is an endocytic macrophage protein strongly regulated by mediators in the inflammatory response

DEFF Research Database (Denmark)

Moeller, Jesper B; Nielsen, Marianne J; Reichhardt, Martin P

2012-01-01

CD163-L1 belongs to the group B scavenger receptor cysteine-rich family of proteins, where the CD163-L1 gene arose by duplication of the gene encoding the hemoglobin scavenger receptor CD163 in late evolution. The current data demonstrate that CD163-L1 is highly expressed and colocalizes with CD163...... on large subsets of macrophages, but in contrast to CD163 the expression is low or absent in monocytes and in alveolar macrophages, glia, and Kupffer cells. The expression of CD163-L1 increases when cultured monocytes are M-CSF stimulated to macrophages, and the expression is further increased by the acute......-phase mediator IL-6 and the anti-inflammatory mediator IL-10 but is suppressed by the proinflammatory mediators IL-4, IL-13, TNF-α, and LPS/IFN-γ. Furthermore, we show that CD163-L1 is an endocytic receptor, which internalizes independently of cross-linking through a clathrin-mediated pathway. Two cytoplasmic...

A note on the uniqueness of 2D elastostatic problems formulated by different types of potential functions

Science.gov (United States)

Guerrero, José Luis Morales; Vidal, Manuel Cánovas; Nicolás, José Andrés Moreno; López, Francisco Alhama

2018-05-01

New additional conditions required for the uniqueness of the 2D elastostatic problems formulated in terms of potential functions for the derived Papkovich-Neuber representations, are studied. Two cases are considered, each of them formulated by the scalar potential function plus one of the rectangular non-zero components of the vector potential function. For these formulations, in addition to the original (physical) boundary conditions, two new additional conditions are required. In addition, for the complete Papkovich-Neuber formulation, expressed by the scalar potential plus two components of the vector potential, the additional conditions established previously for the three-dimensional case in z-convex domain can be applied. To show the usefulness of these new conditions in a numerical scheme two applications are numerically solved by the network method for the three cases of potential formulations.

Investigation of unique hue setting changes with ageing

Institute of Scientific and Technical Information of China (English)

Chenyang Fu; Kaida Xiao; Dimosthenis Karatzas; Sophie Wuerger

2011-01-01

Clromatic sensitivity along the protan, deutan, and tritan lines and the loci of the unique hues (red, green,yellow, blue) for a very large sample (n = 185) of colour-normal observers ranging from 18 to 75 years of age are assessed. Visual judgments are obtained under normal viewing conditions using colour patches on self-luminous display under controlled adaptation conditions. Trivector discrimination thresholds show an increase as a function of age along the protan, deutan, and tritan axes, with the largest increase present along the tritan line, less pronounced shifts in unique hue settings are also observed. Based on the chromatic (protan, deutan, tritan) thresholds and using scaled cone signals, we predict the unique hue changes with ageing. A dependency on age for unique red and unique yellow for predicted hue angle is found. We conclude that the chromatic sensitivity deteriorates significantly with age, whereas the appearance of unique hues is much less affected, remaining almost constant despite the known changes in the ocular media.%@@ Clromatic sensitivity along the protan, deutan, and tritan lines and the loci of the unique hues (red, green,yellow, blue) for a very large sample (n ＝ 185) of colour-normal observers ranging from 18 to 75 years of age are assessed.Visual judgments are obtained under normal viewing conditions using colour patches on self-luminous display under controlled adaptation conditions.Trivector discrimination thresholds show an increase as a function of age along the protan, deutan, and tritan axes, with the largest increase present along the tritan line, less pronounced shifts in unique hue settings are also observed.

The endocytic pathways of a secretory granule membrane protein in HEK293 cells: PAM and EGF traverse a dynamic multivesicular body network together.

Science.gov (United States)

Bäck, Nils; Kanerva, Kristiina; Kurutihalli, Vishwanatha; Yanik, Andrew; Ikonen, Elina; Mains, Richard E; Eipper, Betty A

2017-08-01

Peptidylglycine α-amidating monooxygenase (PAM) is highly expressed in neurons and endocrine cells, where it catalyzes one of the final steps in the biosynthesis of bioactive peptides. PAM is also expressed in unicellular organisms such as Chlamydomonas reinhardtii, which do not store peptides in secretory granules. As for other granule membrane proteins, PAM is retrieved from the cell surface and returned to the trans-Golgi network. This pathway involves regulated entry of PAM into multivesicular body intralumenal vesicles (ILVs). The aim of this study was defining the endocytic pathways utilized by PAM in cells that do not store secretory products in granules. Using stably transfected HEK293 cells, endocytic trafficking of PAM was compared to that of the mannose 6-phosphate (MPR) and EGF (EGFR) receptors, established markers for the endosome to trans-Golgi network and degradative pathways, respectively. As in neuroendocrine cells, PAM internalized by HEK293 cells accumulated in the trans-Golgi network. Based on surface biotinylation, >70% of the PAM on the cell surface was recovered intact after a 4h chase and soluble, bifunctional PAM was produced. Endosomes containing PAM generally contained both EGFR and MPR and ultrastructural analysis confirmed that all three cargos accumulated in ILVs. PAM containing multivesicular bodies made frequent dynamic tubular contacts with younger and older multivesicular bodies. Frequent dynamic contacts were observed between lysosomes and PAM containing early endosomes and multivesicular bodies. The ancient ability of PAM to localize to ciliary membranes, which release bioactive ectosomes, may be related to its ability to accumulate in ILVs and exosomes. Copyright © 2017 Elsevier GmbH. All rights reserved.

IRS-1 acts as an endocytic regulator of IGF-I receptor to facilitate sustained IGF signaling.

Science.gov (United States)

Yoneyama, Yosuke; Lanzerstorfer, Peter; Niwa, Hideaki; Umehara, Takashi; Shibano, Takashi; Yokoyama, Shigeyuki; Chida, Kazuhiro; Weghuber, Julian; Hakuno, Fumihiko; Takahashi, Shin-Ichiro

2018-04-11

Insulin-like growth factor-I receptor (IGF-IR) preferentially regulates the long-term IGF activities including growth and metabolism. Kinetics of ligand-dependent IGF-IR endocytosis determines how IGF induces such downstream signaling outputs. Here, we find that the insulin receptor substrate (IRS)-1 modulates how long ligand-activated IGF-IR remains at the cell surface before undergoing endocytosis in mammalian cells. IRS-1 interacts with the clathrin adaptor complex AP2. IRS-1, but not an AP2-binding-deficient mutant, delays AP2-mediated IGF-IR endocytosis after the ligand stimulation. Mechanistically, IRS-1 inhibits the recruitment of IGF-IR into clathrin-coated structures; for this reason, IGF-IR avoids rapid endocytosis and prolongs its activity on the cell surface. Accelerating IGF-IR endocytosis via IRS-1 depletion induces the shift from sustained to transient Akt activation and augments FoxO-mediated transcription. Our study establishes a new role for IRS-1 as an endocytic regulator of IGF-IR that ensures sustained IGF bioactivity, independent of its classic role as an adaptor in IGF-IR signaling. © 2018, Yoneyama et al.

Alterations in endocytic protein expression with increasing age in the transgenic APP695 V717I London mouse model of amyloid pathology – implications for Alzheimer’s disease

OpenAIRE

Thomas, R. S.; Alsaqatia, M. ed; Bice, J. S.; Hvoslef-Eide, M.; Good, M. A.; Kidd, E. J.

2017-01-01

A major risk factor for the development of Alzheimer’s disease is increasing age but the reason behind this association has not been identified. It is thought that the changes in endocytosis seen in Alzheimer’s disease patients are causal for this condition. Thus we hypothesised that the increased risk of developing Alzheimer’s disease associated with ageing may be due to changes in endocytosis. We investigated using Western blotting whether the expression of endocytic proteins involved in cl...

The collagen receptor uPARAP/Endo180

DEFF Research Database (Denmark)

Engelholm, Lars H; Ingvarsen, Signe; Jürgensen, Henrik J

2009-01-01

The uPAR-associated protein (uPARAP/Endo180), a type-1 membrane protein belonging to the mannose receptor family, is an endocytic receptor for collagen. Through this endocytic function, the protein takes part in a previously unrecognized mechanism of collagen turnover. uPARAP/Endo180 can bind...... and internalize both intact and partially degraded collagens. In some turnover pathways, the function of the receptor probably involves an interplay with certain matrix-degrading proteases whereas, in other physiological processes, redundant mechanisms involving both endocytic and pericellular collagenolysis seem...... in collagen breakdown seems to be involved in invasive tumor growth Udgivelsesdato: 2009...

Functional chloroplasts in metazoan cells - a unique evolutionary strategy in animal life

Directory of Open Access Journals (Sweden)

Krug Patrick J

2009-12-01

. Functional short-term retention was an apomorphy of the Plakobranchoidea, but the subsequent evolution of parapodia enabled slugs to protect kleptoplasts against high irradiance and further prolong plastid survival. We conclude that functional short-term retention was necessary but not sufficient for an adaptive radiation in the Plakobranchoidea, especially in the genus Elysia which comprises a third of all sacoglossan species. The adaptations necessary for long-term chloroplast survival arose independently in species feeding on different algal hosts, providing a valuable study system for examining the parallel evolution of this unique trophic strategy.

Plutonium uniqueness

International Nuclear Information System (INIS)

Silver, G.L.

1984-01-01

A standard is suggested against which the putative uniqueness of plutonium may be tested. It is common folklore that plutonium is unique among the chemical elements because its four common oxidation states can coexist in the same solution. Whether this putative uniqueness appears only during transit to equilibrium, or only at equilibrium, or all of the time, is not generally made clear. But while the folklore may contain some truth, it cannot be put to test until some measure of 'uniqueness' is agreed upon so that quantitative comparisons are possible. One way of measuring uniqueness is as the magnitude of the product of the mole fractions of the element at equilibrium. A 'coexistence index' is defined and discussed. (author)

Unique solvability of a non-linear non-local boundary-value problem for systems of non-linear functional differential equations

Czech Academy of Sciences Publication Activity Database

Dilna, N.; Rontó, András

2010-01-01

Roč. 60, č. 3 (2010), s. 327-338 ISSN 0139-9918 R&D Projects: GA ČR(CZ) GA201/06/0254 Institutional research plan: CEZ:AV0Z10190503 Keywords : non-linear boundary value-problem * functional differential equation * non-local condition * unique solvability * differential inequality Subject RIV: BA - General Mathematics Impact factor: 0.316, year: 2010 http://link.springer.com/article/10.2478%2Fs12175-010-0015-9

A genome-wide immunodetection screen in S. cerevisiae uncovers novel genes involved in lysosomal vacuole function and morphology.

Directory of Open Access Journals (Sweden)

Florante Ricarte

Full Text Available Vacuoles of yeast Saccharomyces cerevisiae are functionally analogous to mammalian lysosomes. Both are cellular organelles responsible for macromolecular degradation, ion/pH homeostasis, and stress survival. We hypothesized that undefined gene functions remain at post-endosomal stage of vacuolar events and performed a genome-wide screen directed at such functions at the late endosome and vacuole interface - ENV genes. The immunodetection screen was designed to identify mutants that internally accumulate precursor form of the vacuolar hydrolase carboxypeptidase Y (CPY. Here, we report the uncovering and initial characterizations of twelve ENV genes. The small size of the collection and the lack of genes previously identified with vacuolar events are suggestive of the intended exclusive functional interface of the screen. Most notably, the collection includes four novel genes ENV7, ENV9, ENV10, and ENV11, and three genes previously linked to mitochondrial processes - MAM3, PCP1, PPE1. In all env mutants, vesicular trafficking stages were undisturbed in live cells as assessed by invertase and active α-factor secretion, as well as by localization of the endocytic fluorescent marker FM4-64 to the vacuole. Several mutants exhibit defects in stress survival functions associated with vacuoles. Confocal fluorescence microscopy revealed the collection to be significantly enriched in vacuolar morphologies suggestive of fusion and fission defects. These include the unique phenotype of lumenal vesicles within vacuoles in the novel env9Δ mutant and severely fragmented vacuoles upon deletion of GET4, a gene recently implicated in tail anchored membrane protein insertion. Thus, our results establish new gene functions in vacuolar function and morphology, and suggest a link between vacuolar and mitochondrial events.

Zeros and uniqueness of Q-difference polynomials of meromorphic ...

Indian Academy of Sciences (India)

Meromorphic functions; Nevanlinna theory; logarithmic order; uniqueness problem; difference-differential polynomial. Abstract. In this paper, we investigate the value distribution of -difference polynomials of meromorphic function of finite logarithmic order, and study the zero distribution of difference-differential polynomials ...

Alterations in endocytic protein expression with increasing age in the transgenic APP695 V717I London mouse model of amyloid pathology: implications for Alzheimer's disease.

Science.gov (United States)

Thomas, Rhian S; Alsaqati, Mouhamed; Bice, Justin S; Hvoslef-Eide, Martha; Good, Mark A; Kidd, Emma J

2017-10-18

A major risk factor for the development of Alzheimer's disease (AD) is increasing age, but the reason behind this association has not been identified. It is thought that the changes in endocytosis seen in AD patients are causal for this condition. Thus, we hypothesized that the increased risk of developing AD associated with ageing may be because of changes in endocytosis. We investigated using Western blotting whether the expression of endocytic proteins involved in clathrin-mediated and clathrin-independent endocytosis are altered by increasing age in a mouse model of amyloid pathology. We used mice transgenic for human amyloid precursor protein containing the V717I London mutation. We compared the London mutation mice with age-matched wild-type (WT) controls at three ages, 3, 9 and 18 months, representing different stages in the development of pathology in this model. Having verified that the London mutation mice overexpressed amyloid precursor protein and β-amyloid, we found that the expression of the smallest isoform of PICALM, a key protein involved in the regulation of clathrin-coated pit formation, was significantly increased in WT mice, but decreased in the London mutation mice with age. PICALM levels in WT 18-month mice and clathrin levels in WT 9-month mice were significantly higher than those in the London mutation mice of the same ages. The expression of caveolin-1, involved in clathrin-independent endocytosis, was significantly increased with age in all mice. Our results suggest that endocytic processes could be altered by the ageing process and such changes could partly explain the association between ageing and AD.

The function of endocytosis in Wnt signaling.

Science.gov (United States)

Brunt, Lucy; Scholpp, Steffen

2018-03-01

Wnt growth factors regulate one of the most important signaling networks during development, tissue homeostasis and disease. Despite the biological importance of Wnt signaling, the mechanism of endocytosis during this process is ill described. Wnt molecules can act as paracrine signals, which are secreted from the producing cells and transported through neighboring tissue to activate signaling in target cells. Endocytosis of the ligand is important at several stages of action: One central function of endocytic trafficking in the Wnt pathway occurs in the source cell. Furthermore, the β-catenin-dependent Wnt ligands require endocytosis for signal activation and to regulate gene transcription in the responding cells. Alternatively, Wnt/β-catenin-independent signaling regulates endocytosis of cell adherence plaques to control cell migration. In this comparative review, we elucidate these three fundamental interconnected functions, which together regulate cellular fate and cellular behavior. Based on established hypotheses and recent findings, we develop a revised picture for the complex function of endocytosis in the Wnt signaling network.

Using Quantum Confinement to Uniquely Identify Devices

Science.gov (United States)

Roberts, J.; Bagci, I. E.; Zawawi, M. A. M.; Sexton, J.; Hulbert, N.; Noori, Y. J.; Young, M. P.; Woodhead, C. S.; Missous, M.; Migliorato, M. A.; Roedig, U.; Young, R. J.

2015-11-01

Modern technology unintentionally provides resources that enable the trust of everyday interactions to be undermined. Some authentication schemes address this issue using devices that give a unique output in response to a challenge. These signatures are generated by hard-to-predict physical responses derived from structural characteristics, which lend themselves to two different architectures, known as unique objects (UNOs) and physically unclonable functions (PUFs). The classical design of UNOs and PUFs limits their size and, in some cases, their security. Here we show that quantum confinement lends itself to the provision of unique identities at the nanoscale, by using fluctuations in tunnelling measurements through quantum wells in resonant tunnelling diodes (RTDs). This provides an uncomplicated measurement of identity without conventional resource limitations whilst providing robust security. The confined energy levels are highly sensitive to the specific nanostructure within each RTD, resulting in a distinct tunnelling spectrum for every device, as they contain a unique and unpredictable structure that is presently impossible to clone. This new class of authentication device operates with minimal resources in simple electronic structures above room temperature.

Unique organizational and functional features of the cytochrome c maturation system in Shewanella oneidensis.

Directory of Open Access Journals (Sweden)

Miao Jin

Full Text Available Shewanella are renowned for their ability to respire on a wide range of electron acceptors, which has been partially accredited to the presence of a large number of the c-type cytochromes. In the model species S. oneidensis MR-1, at least 41 genes encode c-type cytochromes that are predicted to be intact, thereby likely functional. Previously, in-frame deletion mutants for 36 of these genes were obtained and characterized. In this study, first we completed the construction of an entire set of c-type cytochrome mutants utilizing a newly developed att-based mutagenesis approach, which is more effective and efficient than the approach used previously by circumventing the conventional cloning. Second, we investigated the cytochrome c maturation (Ccm system in S. oneidensis. There are two loci predicted to encode components of the Ccm system, SO0259-SO0269 and SO0476-SO0478. The former is proven essential for cytochrome c maturation whereas the latter is dispensable. Unlike the single operon organization observed in other γ-proteobacteria, genes at the SO0259-SO0269 locus are uniquely organized into four operons, ccmABCDE, scyA, SO0265, and ccmFGH-SO0269. Functional analysis revealed that the SO0265 gene rather than the scyA and SO0269 genes are relevant to cytochrome c maturation.

Esperanto: A Unique Model for General Linguistics.

Science.gov (United States)

Dulichenko, Aleksandr D.

1988-01-01

Esperanto presents a unique model for linguistic research by allowing the study of language development from project to fully functioning language. Esperanto provides insight into the growth of polysemy and redundancy, as well as into language universals and the phenomenon of social control. (Author/CB)

Comparative kinomics of human and chimpanzee reveal unique kinship and functional diversity generated by new domain combinations

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Martin Juliette

2008-12-01

Full Text Available Abstract Background Phosphorylation by protein kinases is a common event in many cellular processes. Further, many kinases perform specialized roles and are regulated by non-kinase domains tethered to kinase domain. Perturbation in the regulation of kinases leads to malignancy. We have identified and analysed putative protein kinases encoded in the genome of chimpanzee which is a close evolutionary relative of human. Result The shared core biology between chimpanzee and human is characterized by many orthologous protein kinases which are involved in conserved pathways. Domain architectures specific to chimp/human kinases have been observed. Chimp kinases with unique domain architectures are characterized by deletion of one or more non-kinase domains in the human kinases. Interestingly, counterparts of some of the multi-domain human kinases in chimp are characterized by identical domain architectures but with kinase-like non-kinase domain. Remarkably, out of 587 chimpanzee kinases no human orthologue with greater than 95% sequence identity could be identified for 160 kinases. Variations in chimpanzee kinases compared to human kinases are brought about also by differences in functions of domains tethered to the catalytic kinase domain. For example, the heterodimer forming PB1 domain related to the fold of ubiquitin/Ras-binding domain is seen uniquely tethered to PKC-like chimpanzee kinase. Conclusion Though the chimpanzee and human are evolutionary very close, there are chimpanzee kinases with no close counterpart in the human suggesting differences in their functions. This analysis provides a direction for experimental analysis of human and chimpanzee protein kinases in order to enhance our understanding on their specific biological roles.

Existence and uniqueness of solution for a system of equations of ...

African Journals Online (AJOL)

The existence and uniqueness of solution for a system of equations of microwave heating of biologic issue is discussed. Using the Green function approach we establish the existence and uniqueness of solution. Journal of the Nigerian Association of Mathematical Physics Vol. 8 2004: pp. 177-180 ...

Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins.

Science.gov (United States)

Flavin, William P; Bousset, Luc; Green, Zachary C; Chu, Yaping; Skarpathiotis, Stratos; Chaney, Michael J; Kordower, Jeffrey H; Melki, Ronald; Campbell, Edward M

2017-10-01

Numerous pathological amyloid proteins spread from cell to cell during neurodegenerative disease, facilitating the propagation of cellular pathology and disease progression. Understanding the mechanism by which disease-associated amyloid protein assemblies enter target cells and induce cellular dysfunction is, therefore, key to understanding the progressive nature of such neurodegenerative diseases. In this study, we utilized an imaging-based assay to monitor the ability of disease-associated amyloid assemblies to rupture intracellular vesicles following endocytosis. We observe that the ability to induce vesicle rupture is a common feature of α-synuclein (α-syn) assemblies, as assemblies derived from WT or familial disease-associated mutant α-syn all exhibited the ability to induce vesicle rupture. Similarly, different conformational strains of WT α-syn assemblies, but not monomeric or oligomeric forms, efficiently induced vesicle rupture following endocytosis. The ability to induce vesicle rupture was not specific to α-syn, as amyloid assemblies of tau and huntingtin Exon1 with pathologic polyglutamine repeats also exhibited the ability to induce vesicle rupture. We also observe that vesicles ruptured by α-syn are positive for the autophagic marker LC3 and can accumulate and fuse into large, intracellular structures resembling Lewy bodies in vitro. Finally, we show that the same markers of vesicle rupture surround Lewy bodies in brain sections from PD patients. These data underscore the importance of this conserved endocytic vesicle rupture event as a damaging mechanism of cellular invasion by amyloid assemblies of multiple neurodegenerative disease-associated proteins, and suggest that proteinaceous inclusions such as Lewy bodies form as a consequence of continued fusion of autophagic vesicles in cells unable to degrade ruptured vesicles and their amyloid contents.

Microbial Communities and Their Predicted Metabolic Functions in Growth Laminae of a Unique Large Conical Mat from Lake Untersee, East Antarctica

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Hyunmin Koo

2017-08-01

Full Text Available In this study, we report the distribution of microbial taxa and their predicted metabolic functions observed in the top (U1, middle (U2, and inner (U3 decadal growth laminae of a unique large conical microbial mat from perennially ice-covered Lake Untersee of East Antarctica, using NextGen sequencing of the 16S rRNA gene and bioinformatics tools. The results showed that the U1 lamina was dominated by cyanobacteria, specifically Phormidium sp., Leptolyngbya sp., and Pseudanabaena sp. The U2 and U3 laminae had high abundances of Actinobacteria, Verrucomicrobia, Proteobacteria, and Bacteroidetes. Closely related taxa within each abundant bacterial taxon found in each lamina were further differentiated at the highest taxonomic resolution using the oligotyping method. PICRUSt analysis, which determines predicted KEGG functional categories from the gene contents and abundances among microbial communities, revealed a high number of sequences belonging to carbon fixation, energy metabolism, cyanophycin, chlorophyll, and photosynthesis proteins in the U1 lamina. The functional predictions of the microbial communities in U2 and U3 represented signal transduction, membrane transport, zinc transport and amino acid-, carbohydrate-, and arsenic- metabolisms. The Nearest Sequenced Taxon Index (NSTI values processed through PICRUSt were 0.10, 0.13, and 0.11 for U1, U2, and U3 laminae, respectively. These values indicated a close correspondence with the reference microbial genome database, implying high confidence in the predicted metabolic functions of the microbial communities in each lamina. The distribution of microbial taxa observed in each lamina and their predicted metabolic functions provides additional insight into the complex microbial ecosystem at Lake Untersee, and lays the foundation for studies that will enhance our understanding of the mechanisms responsible for the formation of these unique mat structures and their evolutionary significance.

A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic recycling

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Bai, Zhiyong; Grant, Barth D.

2015-01-01

Endosome-to-Golgi transport is required for the function of many key membrane proteins and lipids, including signaling receptors, small-molecule transporters, and adhesion proteins. The retromer complex is well-known for its role in cargo sorting and vesicle budding from early endosomes, in most cases leading to cargo fusion with the trans-Golgi network (TGN). Transport from recycling endosomes to the TGN has also been reported, but much less is understood about the molecules that mediate this transport step. Here we provide evidence that the F-BAR domain proteins TOCA-1 and TOCA-2 (Transducer of Cdc42 dependent actin assembly), the small GTPase CDC-42 (Cell division control protein 42), associated polarity proteins PAR-6 (Partitioning defective 6) and PKC-3/atypical protein kinase C, and the WAVE actin nucleation complex mediate the transport of MIG-14/Wls and TGN-38/TGN38 cargo proteins from the recycling endosome to the TGN in Caenorhabditis elegans. Our results indicate that CDC-42, the TOCA proteins, and the WAVE component WVE-1 are enriched on RME-1–positive recycling endosomes in the intestine, unlike retromer components that act on early endosomes. Furthermore, we find that retrograde cargo TGN-38 is trapped in early endosomes after depletion of SNX-3 (a retromer component) but is mainly trapped in recycling endosomes after depletion of CDC-42, indicating that the CDC-42–associated complex functions after retromer in a distinct organelle. Thus, we identify a group of interacting proteins that mediate retrograde recycling, and link these proteins to a poorly understood trafficking step, recycling endosome-to-Golgi transport. We also provide evidence for the physiological importance of this pathway in WNT signaling. PMID:25775511

Lectins as endocytic ligands: an assessment of lectin binding and uptake to rabbit conjunctival epithelial cells.

Science.gov (United States)

Qaddoumi, Mohamed; Lee, Vincent H L

2004-07-01

To investigate the binding and uptake pattern of three plant lectins in rabbit conjunctival epithelial cells (RCECs) with respect to their potential for enhancing cellular macromolecular uptake. Three fluorescein-labeled plant lectins (Lycoperison esculentum, TL; Solanum tuberosum, STL; and Ulex europaeus 1, UEA-1) were screened with respect to time-, concentration-, and temperature-dependent binding and uptake. Chitin (30 mg/ml) and L-alpha-fucose (10 mM) were used as inhibitory sugars to correct for nonspecific binding of TL or STL and UEA-1, respectively. Confocal microscopy was used to confirm internalization of STL. The binding and uptake of all three lectins in RCECs was time-dependent (reaching a plateau at 1-2 h period) and saturable at 1-h period. The rank order of affinity constants (km) was STL>TL>UEA-1 with values of 0.39>0.48>4.81 microM, respectively. However, maximal, specific binding/uptake potential was in the order UEA-1>STL>TL with values of 53.7, 52.3, and 15.0 nM/mg of cell protein, respectively. Lectins showed temperature dependence in their uptake, with STL exhibiting the highest endocytic capacity. Internalized STL was visualized by confocal microscopy to be localized to the cell membrane and cytoplasm. Based on favorable binding and uptake characteristics, potato lectin appears to be a useful candidate for further investigation as an ocular drug delivery system.

The N-terminal region of the dopamine D2 receptor, a rhodopsin-like GPCR, regulates correct integration into the plasma membrane and endocytic routes

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Cho, DI; Min, C; Jung, KS; Cheong, SY; Zheng, M; Cheong, SJ; Oak, MH; Cheong, JH; Lee, BK; Kim, KM

2012-01-01

BACKGROUND AND PURPOSE Functional roles of the N-terminal region of rhodopsin-like GPCR family remain unclear. Using dopamine D2 and D3 receptors as a model system, we probed the roles of the N-terminal region in the signalling, intracellular trafficking of receptor proteins, and explored the critical factors that determine the functionality of the N-terminal region. EXPERIMENTAL APPROACH The N-terminal region of the D2 receptor was gradually shortened or switched with that of the D3 receptor or a non-specific sequence (FLAG), or potential N-terminal glycosylation sites were mutated. Effects of these manipulations on surface expression, internalization, post-endocytic behaviours and signalling were determined. KEY RESULTS Shortening the N-terminal region of the D2 receptor enhanced receptor internalization and impaired surface expression and signalling; ligand binding, desensitization and down-regulation were not affected but their association with a particular microdomain, caveolae, was disrupted. Replacement of critical residues within the N-terminal region with the FLAG epitope failed to restore surface expression but partially restored the altered internalization and signalling. When the N-terminal regions were switched between D2 and D3 receptors, cell surface expression pattern of each receptor was switched. Mutations of potential N-terminal glycosylation sites inhibited surface expression but enhanced internalization of D2 receptors. CONCLUSIONS AND IMPLICATIONS Shortening of N-terminus or mutation of glycosylation sites located within the N-terminus enhanced receptor internalization but impaired the surface expression of D2 receptors. The N-terminal region of the D2 receptor, in a sequence-specific manner, controls the receptor's conformation and integration into the plasma membrane, which determine its subcellular localization, intracellular trafficking and signalling properties. PMID:22117524

Loss of Cln3 Function in the Social Amoeba Dictyostelium discoideum Causes Pleiotropic Effects That Are Rescued by Human CLN3

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Huber, Robert J.

2014-01-01

The neuronal ceroid lipofuscinoses (NCL) are a group of inherited, severe neurodegenerative disorders also known as Batten disease. Juvenile NCL (JNCL) is caused by recessive loss-of-function mutations in CLN3, which encodes a transmembrane protein that regulates endocytic pathway trafficking, though its primary function is not yet known. The social amoeba Dictyostelium discoideum is increasingly utilized for neurological disease research and is particularly suited for investigation of protein function in trafficking. Therefore, here we establish new overexpression and knockout Dictyostelium cell lines for JNCL research. Dictyostelium Cln3 fused to GFP localized to the contractile vacuole system and to compartments of the endocytic pathway. cln3− cells displayed increased rates of proliferation and an associated reduction in the extracellular levels and cleavage of the autocrine proliferation repressor, AprA. Mid- and late development of cln3− cells was precocious and cln3− slugs displayed increased migration. Expression of either Dictyostelium Cln3 or human CLN3 in cln3− cells suppressed the precocious development and aberrant slug migration, which were also suppressed by calcium chelation. Taken together, our results show that Cln3 is a pleiotropic protein that negatively regulates proliferation and development in Dictyostelium. This new model system, which allows for the study of Cln3 function in both single cells and a multicellular organism, together with the observation that expression of human CLN3 restores abnormalities in Dictyostelium cln3− cells, strongly supports the use of this new model for JNCL research. PMID:25330233

Loss of Cln3 function in the social amoeba Dictyostelium discoideum causes pleiotropic effects that are rescued by human CLN3.

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Robert J Huber

Full Text Available The neuronal ceroid lipofuscinoses (NCL are a group of inherited, severe neurodegenerative disorders also known as Batten disease. Juvenile NCL (JNCL is caused by recessive loss-of-function mutations in CLN3, which encodes a transmembrane protein that regulates endocytic pathway trafficking, though its primary function is not yet known. The social amoeba Dictyostelium discoideum is increasingly utilized for neurological disease research and is particularly suited for investigation of protein function in trafficking. Therefore, here we establish new overexpression and knockout Dictyostelium cell lines for JNCL research. Dictyostelium Cln3 fused to GFP localized to the contractile vacuole system and to compartments of the endocytic pathway. cln3- cells displayed increased rates of proliferation and an associated reduction in the extracellular levels and cleavage of the autocrine proliferation repressor, AprA. Mid- and late development of cln3- cells was precocious and cln3- slugs displayed increased migration. Expression of either Dictyostelium Cln3 or human CLN3 in cln3- cells suppressed the precocious development and aberrant slug migration, which were also suppressed by calcium chelation. Taken together, our results show that Cln3 is a pleiotropic protein that negatively regulates proliferation and development in Dictyostelium. This new model system, which allows for the study of Cln3 function in both single cells and a multicellular organism, together with the observation that expression of human CLN3 restores abnormalities in Dictyostelium cln3- cells, strongly supports the use of this new model for JNCL research.

Vectorization of morpholino oligomers by the (R-Ahx-R)4 peptide allows efficient splicing correction in the absence of endosomolytic agents.

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Abes, Saïd; Moulton, Hong M; Clair, Philippe; Prevot, Paul; Youngblood, Derek S; Wu, Rebecca P; Iversen, Patrick L; Lebleu, Bernard

2006-12-01

The efficient and non-toxic nuclear delivery of steric-block oligonucleotides (ON) is a prerequisite for therapeutic strategies involving splice correction or exon skipping. Cationic cell penetrating peptides (CPPs) have given rise to much interest for the intracellular delivery of biomolecules, but their efficiency in promoting cytoplasmic or nuclear delivery of oligonucleotides has been hampered by endocytic sequestration and subsequent degradation of most internalized material in endocytic compartments. In the present study, we compared the splice correction activity of three different CPPs conjugated to PMO(705), a steric-block ON targeted against the mutated splicing site of human beta-globin pre-mRNA in the HeLa pLuc705 splice correction model. In contrast to Tat48-60 (Tat) and oligoarginine (R(9)F(2)) PMO(705) conjugates, the 6-aminohexanoic-spaced oligoarginine (R-Ahx-R)(4)-PMO(705) conjugate was able to promote an efficient splice correction in the absence of endosomolytic agents. Our mechanistic investigations about its uptake mechanisms lead to the conclusion that these three vectors are internalized using the same endocytic route involving proteoglycans, but that the (R-Ahx-R)(4)-PMO(705) conjugate has the unique ability to escape from lysosomial fate and to access to the nuclear compartment. This vector, which has displays an extremely low cytotoxicity, the ability to function without chloroquine adjunction and in the presence of serum proteins. It thus offers a promising lead for the development of vectors able to enhance the delivery of therapeutic steric-block ON in clinically relevant models.

The low-density lipoprotein receptor-related protein 1 and amyloid-β clearance in Alzheimer’s disease

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Takahisa eKanekiyo

2014-05-01

Full Text Available Accumulation and aggregation of amyloid-β (Aβ peptides in the brain trigger the development of progressive neurodegeneration and dementia associated with Alzheimer’s disease (AD. Perturbation in Aβ clearance, rather than Aβ production, is likely the cause of sporadic, late-onset AD, which accounts for the majority of AD cases. Since cellular uptake and subsequent degradation constitute a major Aβ clearance pathway, the receptor-mediated endocytosis of Aβ has been intensely investigated. Among Aβ receptors, the low-density lipoprotein receptor-related protein 1 (LRP1 is one of the most studied receptors. LRP1 is a large endocytic receptor for more than 40 ligands, including apolipoprotein E (apoE, α2-macroglobulin and Aβ. Emerging in vitro and in vivo evidence demonstrates that LRP1 is critically involved in brain Aβ clearance. LRP1 is highly expressed in a variety of cell types in the brain including neurons, vascular cells and glial cells, where LRP1 functions to maintain brain homeostasis and control Aβ metabolism. LRP1-mediated endocytosis regulates cellular Aβ uptake by binding to Aβ either directly or indirectly through its co-receptors or ligands. Furthermore, LRP1 regulates several signaling pathways, which also likely influences Aβ endocytic pathways. In this review, we discuss how LRP1 regulates the brain Aβ clearance and how this unique endocytic receptor participates in AD pathogenesis. Understanding of the mechanisms underlying LRP1-mediated Aβ clearance should enable the rational design of novel diagnostic and therapeutic strategies for AD.

'Fractional recovery' analysis of a presynaptic synaptotagmin 1-anchored endocytic protein complex.

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Rajesh Khanna

Full Text Available BACKGROUND: The integral synaptic vesicle protein and putative calcium sensor, synaptotagmin 1 (STG, has also been implicated in synaptic vesicle (SV recovery. However, proteins with which STG interacts during SV endocytosis remain poorly understood. We have isolated an STG-associated endocytic complex (SAE from presynaptic nerve terminals and have used a novel fractional recovery (FR assay based on electrostatic dissociation to identify SAE components and map the complex structure. The location of SAE in the presynaptic terminal was determined by high-resolution quantitative immunocytochemistry at the chick ciliary ganglion giant calyx-type synapse. METHODOLOGY/PRINCIPLE FINDINGS: The first step in FR analysis was to immunoprecipitate (IP the complex with an antibody against one protein component (the IP-protein. The immobilized complex was then exposed to a high salt (1150 mM stress-test that caused shedding of co-immunoprecipitated proteins (co-IP-proteins. A Fractional Recovery ratio (FR: recovery after high salt/recovery with control salt as assayed by Western blot was calculated for each co-IP-protein. These FR values reflect complex structure since an easily dissociated protein, with a low FR value, cannot be intermediary between the IP-protein and a salt-resistant protein. The structure of the complex was mapped and a blueprint generated with a pair of FR analyses generated using two different IP-proteins. The blueprint of SAE contains an AP180/X/STG/stonin 2/intersectin/epsin core (X is unknown and epsin is hypothesized, and an AP2 adaptor, H-/L-clathrin coat and dynamin scission protein perimeter. Quantitative immunocytochemistry (ICA/ICQ method at an isolated calyx-type presynaptic terminal indicates that this complex is associated with STG at the presynaptic transmitter release face but not with STG on intracellular synaptic vesicles. CONCLUSIONS/SIGNIFICANCE: We hypothesize that the SAE serves as a recognition site and also as a

A unique Fock quantization for fields in non-stationary spacetimes

International Nuclear Information System (INIS)

Cortez, Jerónimo; Marugán, Guillermo A. Mena; Olmedo, Javier; Velhinho, José M.

2010-01-01

In curved spacetimes, the lack of criteria for the construction of a unique quantization is a fundamental problem undermining the significance of the predictions of quantum field theory. Inequivalent quantizations lead to different physics. Recently, however, some uniqueness results have been obtained for fields in non-stationary settings. In particular, for vacua that are invariant under the background symmetries, a unitary implementation of the classical evolution suffices to pick up a unique Fock quantization in the case of Klein-Gordon fields with time-dependent mass, propagating in a static spacetime whose spatial sections are three-spheres. In fact, the field equation can be reinterpreted as describing the propagation in a Friedmann-Robertson-Walker spacetime after a suitable scaling of the field by a function of time. For this class of fields, we prove here an even stronger result about the Fock quantization: the uniqueness persists when one allows for linear time-dependent transformations of the field in order to account for a scaling by background functions. In total, paying attention to the dynamics, there exists a preferred choice of quantum field, and only one SO(4)-invariant Fock representation for it that respects the standard probabilistic interpretation along the evolution. The result has relevant implications e.g. in cosmology

Uniqueness and zeros of q-shift difference polynomials

Indian Academy of Sciences (India)

In this paper, we consider the zero distributions of -shift difference polynomials of meromorphic functions with zero order, and obtain two theorems that extend the classical Hayman results on the zeros of differential polynomials to -shift difference polynomials. We also investigate the uniqueness problem of -shift ...

A novel functional role of collagen glycosylation

DEFF Research Database (Denmark)

Jürgensen, Henrik J; Madsen, Daniel H; Ingvarsen, Signe

2011-01-01

Collagens make up the most abundant component of interstitial extracellular matrices and basement membranes. Collagen remodeling is a crucial process in many normal physiological events and in several pathological conditions. Some collagen subtypes contain specific carbohydrate side chains......, the function of which is poorly known. The endocytic collagen receptor urokinase plasminogen activator receptor-associated protein (uPARAP)/Endo180 plays an important role in matrix remodeling through its ability to internalize collagen for lysosomal degradation. uPARAP/Endo180 is a member of the mannose...... receptor protein family. These proteins all include a fibronectin type II domain and a series of C-type lectin-like domains, of which only a minor part possess carbohydrate recognition activity. At least two of the family members, uPARAP/Endo180 and the mannose receptor, interact with collagens...

EphA2 is a functional receptor for the growth factor progranulin.

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Neill, Thomas; Buraschi, Simone; Goyal, Atul; Sharpe, Catherine; Natkanski, Elizabeth; Schaefer, Liliana; Morrione, Andrea; Iozzo, Renato V

2016-12-05

Although the growth factor progranulin was discovered more than two decades ago, the functional receptor remains elusive. Here, we discovered that EphA2, a member of the large family of Ephrin receptor tyrosine kinases, is a functional signaling receptor for progranulin. Recombinant progranulin bound with high affinity to EphA2 in both solid phase and solution. Interaction of progranulin with EphA2 caused prolonged activation of the receptor, downstream stimulation of mitogen-activated protein kinase and Akt, and promotion of capillary morphogenesis. Furthermore, we found an autoregulatory mechanism of progranulin whereby a feed-forward loop occurred in an EphA2-dependent manner that was independent of the endocytic receptor sortilin. The discovery of a functional signaling receptor for progranulin offers a new avenue for understanding the underlying mode of action of progranulin in cancer progression, tumor angiogenesis, and perhaps neurodegenerative diseases. © 2016 Neill et al.

The end of the unique myocardial band: Part II. Clinical and functional considerations

NARCIS (Netherlands)

MacIver, David H.; Partridge, John B.; Agger, Peter; Stephenson, Robert S.; Boukens, Bastiaan J. D.; Omann, Camilla; Jarvis, Jonathan C.; Zhang, Henggui

2018-01-01

Two of the leading concepts of mural ventricular architecture are the unique myocardial band and the myocardial mesh model. We have described, in an accompanying article published in this journal, how the anatomical, histological and high-resolution computed tomographic studies strongly favour the

ARF6 and GASP-1 are post-endocytic sorting proteins selectively involved in the intracellular trafficking of dopamine D2 receptors mediated by GRK and PKC in transfected cells

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Cho, DI; Zheng, M; Min, C; Kwon, KJ; Shin, CY; Choi, HK; Kim, KM

2013-01-01

Background and Purpose GPCRs undergo both homologous and heterologous regulatory processes in which receptor phosphorylation plays a critical role. The protein kinases responsible for each pathway are well established; however, other molecular details that characterize each pathway remain unclear. In this study, the molecular mechanisms that determine the differences in the functional roles and intracellular trafficking between homologous and PKC-mediated heterologous internalization pathways for the dopamine D2 receptor were investigated. Experimental Approach All of the S/T residues located within the intracellular loops of D2 receptor were mutated, and the residues responsible for GRK- and PKC-mediated internalization were determined in HEK-293 cells and SH-SY5Y cells. The functional role of receptor internalization and the cellular components that determine the post-endocytic fate of internalized D2 receptors were investigated in the transfected cells. Key Results T134, T225/S228/S229 and S325 were involved in PKC-mediated D2 receptor desensitization. S229 and adjacent S/T residues mediated the PKC-dependent internalization of D2 receptors, which induced down-regulation and desensitization. S/T residues within the second intracellular loop and T225 were the major residues involved in GRK-mediated internalization of D2 receptors, which induced receptor resensitization. ARF6 mediated the recycling of D2 receptors internalized in response to agonist stimulation. In contrast, GASP-1 mediated the down-regulation of D2 receptors internalized in a PKC-dependent manner. Conclusions and Implications GRK- and PKC-mediated internalizations of D2 receptors occur through different intracellular trafficking pathways and mediate distinct functional roles. Distinct S/T residues within D2 receptors and different sorting proteins are involved in the dissimilar regulation of D2 receptors by GRK2 and PKC. PMID:23082996

Unique battery with an active membrane separator having uniform physico-chemically functionalized ion channels and a method making the same

Science.gov (United States)

Gerald, II, Rex E.; Ruscic, Katarina J [Chicago, IL; Sears, Devin N [Spruce Grove, CA; Smith, Luis J [Natick, MA; Klingler, Robert J [Glenview, IL; Rathke, Jerome W [Homer Glen, IL

2012-02-21

The invention relates to a unique battery having an active, porous membrane and method of making the same. More specifically the invention relates to a sealed battery system having a porous, metal oxide membrane with uniform, physicochemically functionalized ion channels capable of adjustable ionic interaction. The physicochemically-active porous membrane purports dual functions: an electronic insulator (separator) and a unidirectional ion-transporter (electrolyte). The electrochemical cell membrane is activated for the transport of ions by contiguous ion coordination sites on the interior two-dimensional surfaces of the trans-membrane unidirectional pores. The membrane material is designed to have physicochemical interaction with ions. Control of the extent of the interactions between the ions and the interior pore walls of the membrane and other materials, chemicals, or structures contained within the pores provides adjustability of the ionic conductivity of the membrane.

Synthetic Biology of Cyanobacteria: Unique Challenges and Opportunities

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Bertram M Berla

2013-08-01

Full Text Available Photosynthetic organisms, and especially cyanobacteria, hold great promise as sources of renewably-produced fuels, bulk and specialty chemicals, and nutritional products. Synthetic biology tools can help unlock cyanobacteria’s potential for these functions, but unfortunately tool development for these organisms has lagged behind that for S. cerevisiae and E. coli. While these organisms may in many cases be more difficult to work with as ‘chassis’ strains for synthetic biology than certain heterotrophs, the unique advantages of autotrophs in biotechnology applications as well as the scientific importance of improved understanding of photosynthesis warrant the development of these systems into something akin to a ‘green E. coli’. In this review, we highlight unique challenges and opportunities for development of synthetic biology approaches in cyanobacteria. We review classical and recently developed methods for constructing targeted mutants in various cyanobacterial strains, and offer perspective on what genetic tools might most greatly expand the ability to engineer new functions in such strains. Similarly, we review what genetic parts are most needed for the development of cyanobacterial synthetic biology. Finally, we highlight recent methods to construct genome-scale models of cyanobacterial metabolism and to use those models to measure properties of autotrophic metabolism. Throughout this paper, we discuss some of the unique challenges of a diurnal, autotrophic lifestyle along with how the development of synthetic biology and biotechnology in cyanobacteria must fit within those constraints.

Unique contributions of emotion regulation and executive functions in predicting the quality of parent-child interaction behaviors.

Science.gov (United States)

Shaffer, Anne; Obradović, Jelena

2017-03-01

Parenting is a cognitive, emotional, and behavioral endeavor, yet limited research investigates parents' executive functions and emotion regulation as predictors of how parents interact with their children. The current study is a multimethod investigation of parental self-regulation in relation to the quality of parenting behavior and parent-child interactions in a diverse sample of parents and kindergarten-age children. Using path analyses, we tested how parent executive functions (inhibitory control) and lack of emotion regulation strategies uniquely relate to both sensitive/responsive behaviors and positive/collaborative behaviors during observed interaction tasks. In our analyses, we accounted for parent education, financial stress, and social support as socioeconomic factors that likely relate to parent executive function and emotion regulation skills. In a diverse sample of primary caregivers (N = 102), we found that direct assessment of parent inhibitory control was positively associated with sensitive/responsive behaviors, whereas parent self-reported difficulties in using emotion regulation strategies were associated with lower levels of positive and collaborative dyadic behaviors. Parent education and financial stress predicted inhibitory control, and social support predicted emotion regulation difficulties; parent education was also a significant predictor of sensitive/responsive behaviors. Greater inhibitory control skills and fewer difficulties identifying effective emotion regulation strategies were not significantly related in our final path model. We discuss our findings in the context of current and emerging parenting interventions. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Stigma: a Unique Source of Distress for Family Members of Individuals with Mental Illness.

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Muralidharan, Anjana; Lucksted, Alicia; Medoff, Deborah; Fang, Li Juan; Dixon, Lisa

2016-07-01

To distinguish the impact of mental illness stigma from that of other negative caregiving experiences, this study examined the unique relationships between stigma and caregiver/family functioning. Adult relatives (n = 437) of individuals with mental illness completed questionnaires regarding caregiving experiences, distress, empowerment, and family functioning, as part of a larger study. Regression analyses examined the relationship between stigma and caregiver/family variables, while controlling for other negative caregiving experiences. Stigma was uniquely associated with caregiver distress, empowerment, and family functioning. Mental illness stigma is a potent source of distress for families and an important target of family services.

[Uniqueness seeking behavior as a self-verification: an alternative approach to the study of uniqueness].

Science.gov (United States)

Yamaoka, S

1995-06-01

Uniqueness theory explains that extremely high perceived similarity between self and others evokes negative emotional reactions and causes uniqueness seeking behavior. However, the theory conceptualizes similarity so ambiguously that it appears to suffer from low predictive validity. The purpose of the current article is to propose an alternative explanation of uniqueness seeking behavior. It posits that perceived uniqueness deprivation is a threat to self-concepts, and therefore causes self-verification behavior. Two levels of self verification are conceived: one based on personal categorization and the other on social categorization. The present approach regards uniqueness seeking behavior as the personal-level self verification. To test these propositions, a 2 (very high or moderate similarity information) x 2 (with or without outgroup information) x 2 (high or low need for uniqueness) between-subject factorial-design experiment was conducted with 95 university students. Results supported the self-verification approach, and were discussed in terms of effects of uniqueness deprivation, levels of self-categorization, and individual differences in need for uniqueness.

Classical many-particle systems with unique disordered ground states

Science.gov (United States)

Zhang, G.; Stillinger, F. H.; Torquato, S.

2017-10-01

Classical ground states (global energy-minimizing configurations) of many-particle systems are typically unique crystalline structures, implying zero enumeration entropy of distinct patterns (aside from trivial symmetry operations). By contrast, the few previously known disordered classical ground states of many-particle systems are all high-entropy (highly degenerate) states. Here we show computationally that our recently proposed "perfect-glass" many-particle model [Sci. Rep. 6, 36963 (2016), 10.1038/srep36963] possesses disordered classical ground states with a zero entropy: a highly counterintuitive situation . For all of the system sizes, parameters, and space dimensions that we have numerically investigated, the disordered ground states are unique such that they can always be superposed onto each other or their mirror image. At low energies, the density of states obtained from simulations matches those calculated from the harmonic approximation near a single ground state, further confirming ground-state uniqueness. Our discovery provides singular examples in which entropy and disorder are at odds with one another. The zero-entropy ground states provide a unique perspective on the celebrated Kauzmann-entropy crisis in which the extrapolated entropy of a supercooled liquid drops below that of the crystal. We expect that our disordered unique patterns to be of value in fields beyond glass physics, including applications in cryptography as pseudorandom functions with tunable computational complexity.

The biology, function and clinical implications of exosomes in lung cancer.

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Zhou, Li; Lv, Tangfeng; Zhang, Qun; Zhu, Qingqing; Zhan, Ping; Zhu, Suhua; Zhang, Jianya; Song, Yong

2017-10-28

Exosomes are 30-100 nm small membrane vesicles of endocytic origin that are secreted by all types of cells, and can also be found in various body fluids. Increasing evidence implicates that exosomes confer stability and can deliver their cargos such as proteins and nucleic acids to specific cell types, which subsequently serve as important messengers and carriers in lung carcinogenesis. Here, we describe the biogenesis and components of exosomes mainly in lung cancer, we summarize their function in lung carcinogenesis (epithelial mesenchymal transition, oncogenic cell transformation, angiogenesis, metastasis and immune response in tumor microenvironment), and importantly we focus on the clinical potential of exosomes as biomarkers and therapeutics in lung cancer. In addition, we also discuss current challenges that might impede the clinical use of exosomes. Further studies on the functional roles of exosomes in lung cancer requires thorough research. Copyright © 2017 Elsevier B.V. All rights reserved.

The Dissociative Subtype of Posttraumatic Stress Disorder: Unique Resting-State Functional Connectivity of Basolateral and Centromedial Amygdala Complexes.

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Nicholson, Andrew A; Densmore, Maria; Frewen, Paul A; Théberge, Jean; Neufeld, Richard Wj; McKinnon, Margaret C; Lanius, Ruth A

2015-09-01

Previous studies point towards differential connectivity patterns among basolateral (BLA) and centromedial (CMA) amygdala regions in patients with posttraumatic stress disorder (PTSD) as compared with controls. Here we describe the first study to compare directly connectivity patterns of the BLA and CMA complexes between PTSD patients with and without the dissociative subtype (PTSD+DS and PTSD-DS, respectively). Amygdala connectivity to regulatory prefrontal regions and parietal regions involved in consciousness and proprioception were expected to differ between these two groups based on differential limbic regulation and behavioral symptoms. PTSD patients (n=49) with (n=13) and without (n=36) the dissociative subtype and age-matched healthy controls (n=40) underwent resting-state fMRI. Bilateral BLA and CMA connectivity patterns were compared using a seed-based approach via SPM Anatomy Toolbox. Among patients with PTSD, the PTSD+DS group exhibited greater amygdala functional connectivity to prefrontal regions involved in emotion regulation (bilateral BLA and left CMA to the middle frontal gyrus and bilateral CMA to the medial frontal gyrus) as compared with the PTSD-DS group. In addition, the PTSD+DS group showed greater amygdala connectivity to regions involved in consciousness, awareness, and proprioception-implicated in depersonalization and derealization (left BLA to superior parietal lobe and cerebellar culmen; left CMA to dorsal posterior cingulate and precuneus). Differences in amygdala complex connectivity to specific brain regions parallel the unique symptom profiles of the PTSD subgroups and point towards unique biological markers of the dissociative subtype of PTSD.

Plastic-casting intrinsic-surface unique identifier (tag)

International Nuclear Information System (INIS)

Palm, R.G.; De Volpi, A.

1995-04-01

This report describes the development of an authenticated intrinsic-surf ace tagging method for unique- identification of controlled items. Although developed for control of items limited by an arms control treaty, this method has other potential applications to keep track of critical or high-value items. Each tag (unique-identifier) consists of the intrinsic, microscopic surface topography of a small designated area on a controlled item. It is implemented by making a baseline plastic casting of the designated tag area and usually placing a cover (for example, a bar-code label) over this area to protect the surface from environmental alteration. The plastic casting is returned to a laboratory and prepared for high-resolution scanning electron microscope imaging. Several images are digitized and stored for use as a standard for authentication of castings taken during future inspections. Authentication is determined by numerically comparing digital images. Commercially available hardware and software are used for this tag. Tag parameters are optimized, so unique casting images are obtained from original surfaces, and images obtained from attempted duplicate surfaces are detected. This optimization uses the modulation transfer function, a first principle of image analysis, to determine the parameters. Surface duplication experiments confirmed the optimization

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

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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.

Uniqueness for inverse problems of determining orders of multi-term time-fractional derivatives of diffusion equation

OpenAIRE

Li, Zhiyuan; Yamamoto, Masahiro

2014-01-01

This article proves the uniqueness for two kinds of inverse problems of identifying fractional orders in diffusion equations with multiple time-fractional derivatives by pointwise observation. By means of eigenfunction expansion and Laplace transform, we reduce the uniqueness for our inverse problems to the uniqueness of expansions of some special function and complete the proof.

Addressing Unison and Uniqueness of Reliability and Safety for Better Integration

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Huang, Zhaofeng; Safie, Fayssal

2015-01-01

For a long time, both in theory and in practice, safety and reliability have not been clearly differentiated, which leads to confusion, inefficiency, and sometime counter-productive practices in executing each of these two disciplines. It is imperative to address the uniqueness and the unison of these two disciplines to help both disciplines become more effective and to promote a better integration of the two for enhancing safety and reliability in our products as an overall objective. There are two purposes of this paper. First, it will investigate the uniqueness and unison of each discipline and discuss the interrelationship between the two for awareness and clarification. Second, after clearly understanding the unique roles and interrelationship between the two in a product design and development life cycle, we offer suggestions to enhance the disciplines with distinguished and focused roles, to better integrate the two, and to improve unique sets of skills and tools of reliability and safety processes. From the uniqueness aspect, the paper identifies and discusses the respective uniqueness of reliability and safety from their roles, accountability, nature of requirements, technical scopes, detailed technical approaches, and analysis boundaries. It is misleading to equate unreliable to unsafe, since a safety hazard may or may not be related to the component, sub-system, or system functions, which are primarily what reliability addresses. Similarly, failing-to-function may or may not lead to hazard events. Examples will be given in the paper from aerospace, defense, and consumer products to illustrate the uniqueness and differences between reliability and safety. From the unison aspect, the paper discusses what the commonalities between reliability and safety are, and how these two disciplines are linked, integrated, and supplemented with each other to accomplish the customer requirements and product goals. In addition to understanding the uniqueness in

Unique Description for Single Transverse Spin Asymmetries in DIS and Hadronic Collisions

International Nuclear Information System (INIS)

Yuan Feng

2007-01-01

We derive a unique formula for the single-transverse-spin asymmetry in semi-inclusive hadron production in deep inelastic scattering, valid for all transverse momentum region. Based on this, we further study the integrated asymmetry weighted with transverse-momentum. They can be evaluated in terms of the twist-three quark-gluon correlation functions, which are responsible for the single spin asymmetry in single inclusive hadron production in hadronic collisions. By using the fitted twist-three functions from the hadronic collision data, we find a consistent description for SSAs in deep inelastic scattering. This demonstrates that we have a unique picture for SSAs in these two processes, and shall provide important guidelines for future studies

Uniquely Strongly Clean Group Rings

Institute of Scientific and Technical Information of China (English)

WANG XIU-LAN

2012-01-01

A ring R is called clean if every element is the sum of an idempotent and a unit,and R is called uniquely strongly clean (USC for short) if every element is uniquely the sum of an idempotent and a unit that commute.In this article,some conditions on a ring R and a group G such that RG is clean are given.It is also shown that if G is a locally finite group,then the group ring RG is USC if and only if R is USC,and G is a 2-group.The left uniquely exchange group ring,as a middle ring of the uniquely clean ring and the USC ring,does not possess this property,and so does the uniquely exchange group ring.

Quantification of cytosolic interactions identifies Ede1 oligomers as key organizers of endocytosis.

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Boeke, Dominik; Trautmann, Susanne; Meurer, Matthias; Wachsmuth, Malte; Godlee, Camilla; Knop, Michael; Kaksonen, Marko

2014-11-03

Clathrin-mediated endocytosis is a highly conserved intracellular trafficking pathway that depends on dynamic protein-protein interactions between up to 60 different proteins. However, little is known about the spatio-temporal regulation of these interactions. Using fluorescence (cross)-correlation spectroscopy in yeast, we tested 41 previously reported interactions in vivo and found 16 to exist in the cytoplasm. These detected cytoplasmic interactions included the self-interaction of Ede1, homolog of mammalian Eps15. Ede1 is the crucial scaffold for the organization of the early stages of endocytosis. We show that oligomerization of Ede1 through its central coiled coil domain is necessary for its localization to the endocytic site and we link the oligomerization of Ede1 to its function in locally concentrating endocytic adaptors and organizing the endocytic machinery. Our study sheds light on the importance of the regulation of protein-protein interactions in the cytoplasm for the assembly of the endocytic machinery in vivo. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

Problem of uniqueness in the renewal process generated by the uniform distribution

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D. Ugrin-Šparac

1992-01-01

Full Text Available The renewal process generated by the uniform distribution, when interpreted as a transformation of the uniform distribution into a discrete distribution, gives rise to the question of uniqueness of the inverse image. The paper deals with a particular problem from the described domain, that arose in the construction of a complex stochastic test intended to evaluate pseudo-random number generators. The connection of the treated problem with the question of a unique integral representation of Gamma-function is also mentioned.

Niche partitioning of feeding microhabitats produces a unique function for herbivorous rabbitfishes (Perciformes, Siganidae) on coral reefs

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Fox, R. J.; Bellwood, D. R.

2013-03-01

Niche theory predicts that coexisting species minimise competition by evolving morphological or behavioural specialisations that allow them to spread out along resource axes such as space, diet and temporal activity. These specialisations define how a species interacts with its environment and, by extension, determine its functional role. Here, we examine the feeding niche of three species of coral reef-dwelling rabbitfishes (Siganidae, Siganus). By comparing aspects of their feeding behaviour (bite location, bite rate, foraging distance) with that of representative species from two other abundant herbivorous fish families, the parrotfishes (Labridae, Scarus) and surgeonfishes (Acanthuridae, Acanthurus), we examine whether rabbitfishes have a feeding niche distinct from other members of the herbivore guild. Measurements of the penetration of the fishes' snouts and bodies into reef concavities when feeding revealed that rabbitfish fed to a greater degree from reef crevices and interstices than other herbivores. There was just a 40 % overlap in the penetration-depth niche between rabbitfish and surgeonfish and a 45 % overlap between rabbitfish and parrotfish, compared with the almost complete niche overlap (95 %) recorded for parrotfish and surgeonfish along this spatial niche axis. Aspects of the morphology of rabbitfish which may contribute to this niche segregation include a comparatively longer, narrower snout and narrower head. Our results suggest that sympatric coexistence of rabbitfish and other reef herbivores is facilitated by segregation along a spatial (and potentially dietary) axis. This segregation results in a unique functional role for rabbitfishes among roving herbivores that of "crevice-browser": a group that specifically feeds on crevice-dwelling algal or benthic organisms. This functional trait may have implications for reef ecosystem processes in terms of controlling the successional development of crevice-based algal communities, reducing their

Transcriptome profile and unique genetic evolution of positively selected genes in yak lungs.

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Lan, DaoLiang; Xiong, XianRong; Ji, WenHui; Li, Jian; Mipam, Tserang-Donko; Ai, Yi; Chai, ZhiXin

2018-04-01

The yak (Bos grunniens), which is a unique bovine breed that is distributed mainly in the Qinghai-Tibetan Plateau, is considered a good model for studying plateau adaptability in mammals. The lungs are important functional organs that enable animals to adapt to their external environment. However, the genetic mechanism underlying the adaptability of yak lungs to harsh plateau environments remains unknown. To explore the unique evolutionary process and genetic mechanism of yak adaptation to plateau environments, we performed transcriptome sequencing of yak and cattle (Bos taurus) lungs using RNA-Seq technology and a subsequent comparison analysis to identify the positively selected genes in the yak. After deep sequencing, a normal transcriptome profile of yak lung that containing a total of 16,815 expressed genes was obtained, and the characteristics of yak lungs transcriptome was described by functional analysis. Furthermore, Ka/Ks comparison statistics result showed that 39 strong positively selected genes are identified from yak lungs. Further GO and KEGG analysis was conducted for the functional annotation of these genes. The results of this study provide valuable data for further explorations of the unique evolutionary process of high-altitude hypoxia adaptation in yaks in the Tibetan Plateau and the genetic mechanism at the molecular level.

Coupling of exocytosis and endocytosis at the presynaptic active zone.

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Maritzen, Tanja; Haucke, Volker

2018-02-01

Brain function depends on the ability of neurons to communicate with each other via the regulated exocytosis of neurotransmitter-containing synaptic vesicles (SVs) at specialized presynaptic release sites termed active zones (AZs). The presynaptic AZ comprises an assembly of large multidomain proteins that link the machinery for vesicle fusion to sites of voltage-dependent Ca 2+ entry. Following SV fusion at AZ release sites SV membranes are retrieved by compensatory endocytosis, and SVs are reformed. Recent data suggest that Ca 2+ -triggered SV exocytosis at AZs and endocytic retrieval of SVs may be functionally and physically linked. Here we discuss the evidence supporting such exo-endocytic coupling as well as possible modes and mechanisms that may underlie coupling of exocytosis and endocytosis at and around AZs in presynaptic nerve terminals. As components of the exo-endocytic machinery at synapses have been linked to neurological and neuropsychiatric disorders, understanding the mechanisms that couple exocytosis and endocytosis at AZs may be of importance for developing novel therapies to treat these diseases. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

The uniqueness of the solution for the definite problem of a parabolic variational inequality

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Liping Song

2016-12-01

Full Text Available Abstract The uniqueness of the solution for the definite problem of a parabolic variational inequality is proved. The problem comes from the study of the optimal exercise strategies for the perpetual executive stock options with unrestricted exercise in financial market. Because the variational inequality is degenerate and the obstacle condition contains the partial derivative of an unknown function, it makes the theoretical study of the definite problem of the variational inequality problem very difficult. Firstly, the property which the value function satisfies is derived by applying the Jensen inequality. Then the uniqueness of the solution is proved by using this property and maximum principles.

Factors Affecting Quality of Life at Different Intervals After Treatment of Localized Prostate Cancer: Unique Influence of Treatment Decision Making Satisfaction, Personality and Sexual Functioning.

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Victorson, David E; Schuette, Stephanie; Schalet, Benjamin D; Kundu, Shilajit D; Helfand, Brian T; Novakovic, Kristian; Sufrin, Nathaniel; McGuire, Michael; Brendler, Charles

2016-11-01

Using patient reported outcomes measures we identified the most informative set of factors associated with quality of life in a large sample of men treated for localized prostate cancer. We examined relationships with quality of life using FACIT (Functional Assessment of Chronic Illness Therapy). We also hypothesized variables in a sample of men diagnosed with localized prostate cancer who represented different time points since treatment, including less than 12 months in 70, 1 to 3 years in 344, greater than 3 to 5 years in 291 and greater than 5 years in 97. Correlative measures included subscales of MAX-PC (Memorial Anxiety Scale for Prostate Cancer), short forms of PROMIS® and SOMS (Surgical Outcomes Measurement System), TDM-SATS (Treatment Decision-Making Satisfaction Scale) and subscales of the BFI (Big Five Inventory) of personality. Quality of life was significantly associated with hypothesized variables across different time cohorts. In regression models several factors accounted for most of the variability in quality of life scores depending on time since treatment, including 47%, 22%, 29% and 27% at less than 12 months, 1 to 3 years, greater than 3 to 5 years and greater than 5 years, respectively. Upon examining the unique contribution of these variables, treatment decision making satisfaction was the only variable to have a significant and unique contribution to quality of life across all 4 time cohorts (standardized coefficients 0.33, 0.27, 0.31 and 0.49, respectively, p personality style also had unique associations with quality of life (standardized coefficients 0.25 and -0.20, respectively). When considering the short-term and the longer term quality of life of a man after treatment for localized prostate cancer, our findings highlight the importance of treatment decision making satisfaction, erectile function and personality. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights

Unique cell type-specific junctional complexes in vascular endothelium of human and rat liver sinusoids.

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Cyrill Géraud

Full Text Available Liver sinusoidal endothelium is strategically positioned to control access of fluids, macromolecules and cells to the liver parenchyma and to serve clearance functions upstream of the hepatocytes. While clearance of macromolecular debris from the peripheral blood is performed by liver sinusoidal endothelial cells (LSECs using a delicate endocytic receptor system featuring stabilin-1 and -2, the mannose receptor and CD32b, vascular permeability and cell trafficking are controlled by transcellular pores, i.e. the fenestrae, and by intercellular junctional complexes. In contrast to blood vascular and lymphatic endothelial cells in other organs, the junctional complexes of LSECs have not yet been consistently characterized in molecular terms. In a comprehensive analysis, we here show that LSECs express the typical proteins found in endothelial adherens junctions (AJ, i.e. VE-cadherin as well as α-, β-, p120-catenin and plakoglobin. Tight junction (TJ transmembrane proteins typical of endothelial cells, i.e. claudin-5 and occludin, were not expressed by rat LSECs while heterogenous immunreactivity for claudin-5 was detected in human LSECs. In contrast, junctional molecules preferentially associating with TJ such as JAM-A, B and C and zonula occludens proteins ZO-1 and ZO-2 were readily detected in LSECs. Remarkably, among the JAMs JAM-C was considerably over-expressed in LSECs as compared to lung microvascular endothelial cells. In conclusion, we show here that LSECs form a special kind of mixed-type intercellular junctions characterized by co-occurrence of endothelial AJ proteins, and of ZO-1 and -2, and JAMs. The distinct molecular architecture of the intercellular junctional complexes of LSECs corroborates previous ultrastructural findings and provides the molecular basis for further analyses of the endothelial barrier function of liver sinusoids under pathologic conditions ranging from hepatic inflammation to formation of liver metastasis.

Integration by parts and by substitution unified, Green's Theorem and uniqueness for ODEs

OpenAIRE

Cid, J. A.; Pouso, Rodrigo López

2015-01-01

We present a rather unknown version of the change of variables formula for non-autonomous functions. We will show that this formula is equivalent to Green's Theorem for regions of the plane bounded by the graphs of two continuously differentiable functions. Besides, the formula has interesting applications in the uniqueness of solution of ordinary differential equations.

«Paralipomena» on uniqueness in inverse scattering from a finite number of data

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R. Persico

2007-06-01

Full Text Available This paper shows new proof of non-uniqueness of the solution for the retrieving of a compact-supported function starting from a finite number of samples of its spectrum. As will be shown, this is relevant for linear inverse scattering problems, that in many cases can be recast as the reconstruction of a compact supported function from a finite set of samples of its spectrum. Since this reconstruction is not unique, from a practical point of view, any linear inverse scattering algorithm that can be recast in terms of a Fourier relationship between unknowns and data necessarily «trusts» on the absence of invisible objects in the particular situation at hand.

Measuring Environmental Factors: Unique and Overlapping International Classification of Functioning, Disability and Health Coverage of 5 Instruments.

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Heinemann, Allen W; Miskovic, Ana; Semik, Patrick; Wong, Alex; Dashner, Jessica; Baum, Carolyn; Magasi, Susan; Hammel, Joy; Tulsky, David S; Garcia, Sofia F; Jerousek, Sara; Lai, Jin-Shei; Carlozzi, Noelle E; Gray, David B

2016-12-01

To describe the unique and overlapping content of the newly developed Environmental Factors Item Banks (EFIB) and 7 legacy environmental factor instruments, and to evaluate the EFIB's construct validity by examining associations with legacy instruments. Cross-sectional, observational cohort. Community. A sample of community-dwelling adults with stroke, spinal cord injury, and traumatic brain injury (N=568). None. EFIB covering domains of the built and natural environment; systems, services, and policies; social environment; and access to information and technology; the Craig Hospital Inventory of Environmental Factors (CHIEF) short form; the Facilitators and Barriers Survey/Mobility (FABS/M) short form; the Home and Community Environment Instrument (HACE); the Measure of the Quality of the Environment (MQE) short form; and 3 of the Patient Reported Outcomes Measurement Information System's (PROMIS) Quality of Social Support measures. The EFIB and legacy instruments assess most of the International Classification of Functioning, Disability and Health (ICF) environmental factors chapters, including chapter 1 (products and technology; 75 items corresponding to 11 codes), chapter 2 (natural environment and human-made changes; 31 items corresponding to 7 codes), chapter 3 (support and relationships; 74 items corresponding to 7 codes), chapter 4 (attitudes; 83 items corresponding to 8 codes), and chapter 5 (services, systems, and policies; 72 items corresponding to 16 codes). Construct validity is provided by moderate correlations between EFIB measures and the CHIEF, MQE barriers, HACE technology mobility, FABS/M community built features, and PROMIS item banks and by small correlations with other legacy instruments. Only 5 of the 66 legacy instrument correlation coefficients are moderate, suggesting they measure unique aspects of the environment, whereas all intra-EFIB correlations were at least moderate. The EFIB measures provide a brief and focused assessment of ICF

Unique properties of Drosophila spermatocyte primary cilia

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Maria Giovanna Riparbelli

2013-09-01

The primary cilium is an essential organelle required for animal development and adult homeostasis that is found on most animal cells. The primary cilium contains a microtubule-based axoneme cytoskeleton that typically grows from the mother centriole in G0/G1 phase of the cell cycle as a membrane-bound compartment that protrudes from the cell surface. A unique system of bidirectional transport, intraflagellar transport (IFT, maintains the structure and function of cilia. While the axoneme is dynamic, growing and shrinking at its tip, at the same time it is very stable to the effects of microtubule-targeting drugs. The primary cilia found on Drosophila spermatocytes diverge from the general rules of primary cilium biology in several respects. Among these unique attributes, spermatocyte cilia assemble from all four centrioles in an IFT-independent manner in G2 phase, and persist continuously through two cell divisions. Here, we show that Drosophila spermatocyte primary cilia are extremely sensitive to microtubule-targeting drugs, unlike their mammalian counterparts. Spermatocyte cilia and their axonemes fail to assemble or be maintained upon nocodazole treatment, while centriole replication appears unperturbed. On the other hand, paclitaxel (Taxol, a microtubule-stabilizing drug, disrupted transition zone assembly and anchoring to the plasma membrane while causing spermatocyte primary cilia to grow extensively long during the assembly/elongation phase, but did not overtly affect the centrioles. However, once assembled to their mature length, spermatocyte cilia appeared unaffected by Taxol. The effects of these drugs on axoneme dynamics further demonstrate that spermatocyte primary cilia are endowed with unique assembly properties.

Modeling Rare and Unique Documents: Using FRBR[subscript OO]/CIDOC CRM

Science.gov (United States)

Le Boeuf, Patrick

2012-01-01

Both the library and the museum communities have developed conceptual models for the information they produce about the collections they hold: FRBR (Functional Requirements for Bibliographic Records) and CIDOC CRM (Conceptual Reference Model). But neither proves perfectly adequate when it comes to some specific types of rare and unique materials:…

Cancer: Unique to Older Adults

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... A to Z › Cancer › Unique to Older Adults Font size A A A Print Share Glossary Unique ... group with other older people with the same type of cancer. Researchers have found that support groups ...

Body composition and reproductive function exert unique influences on indices of bone health in exercising women.

Science.gov (United States)

Mallinson, Rebecca J; Williams, Nancy I; Hill, Brenna R; De Souza, Mary Jane

2013-09-01

Reproductive function, metabolic hormones, and lean mass have been observed to influence bone metabolism and bone mass. It is unclear, however, if reproductive, metabolic and body composition factors play unique roles in the clinical measures of areal bone mineral density (aBMD) and bone geometry in exercising women. This study compares lumbar spine bone mineral apparent density (BMAD) and estimates of femoral neck cross-sectional moment of inertia (CSMI) and cross-sectional area (CSA) between exercising ovulatory (Ov) and amenorrheic (Amen) women. It also explores the respective roles of reproductive function, metabolic status, and body composition on aBMD, lumbar spine BMAD and femoral neck CSMI and CSA, which are surrogate measures of bone strength. Among exercising women aged 18-30 years, body composition, aBMD, and estimates of femoral neck CSMI and CSA were assessed by dual-energy x-ray absorptiometry. Lumbar spine BMAD was calculated from bone mineral content and area. Estrone-1-glucuronide (E1G) and pregnanediol glucuronide were measured in daily urine samples collected for one cycle or monitoring period. Fasting blood samples were collected for measurement of leptin and total triiodothyronine. Ov (n = 37) and Amen (n = 45) women aged 22.3 ± 0.5 years did not differ in body mass, body mass index, and lean mass; however, Ov women had significantly higher percent body fat than Amen women. Lumbar spine aBMD and BMAD were significantly lower in Amen women compared to Ov women (p < 0.001); however, femoral neck CSA and CSMI were not different between groups. E1G cycle mean and age of menarche were the strongest predictors of lumbar spine aBMD and BMAD, together explaining 25.5% and 22.7% of the variance, respectively. Lean mass was the strongest predictor of total hip and femoral neck aBMD as well as femoral neck CSMI and CSA, explaining 8.5-34.8% of the variance. Upon consideration of several potential osteogenic stimuli, reproductive function appears to play

Uniqueness in time measurement

International Nuclear Information System (INIS)

Lorenzen, P.

1981-01-01

According to P. Janich a clock is defined as an apparatus in which a point ( hand ) is moving uniformly on a straight line ( path ). For the definition of uniformly first the scaling (as a constant ratio of velocities) is defined without clocks. Thereafter the uniqueness of the time measurement can be proved using the prove of scaling of all clocks. But the uniqueness can be defined without scaling, as it is pointed out here. (orig.) [de

Shared and Unique Proteins in Human, Mouse and Rat Saliva Proteomes: Footprints of Functional Adaptation

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Robert C. Karn

2013-12-01

Full Text Available The overall goal of our study was to compare the proteins found in the saliva proteomes of three mammals: human, mouse and rat. Our first objective was to compare two human proteomes with very different analysis depths. The 89 shared proteins in this comparison apparently represent a core of highly-expressed human salivary proteins. Of the proteins unique to each proteome, one-half to 2/3 lack signal peptides and probably are contaminants instead of less highly-represented salivary proteins. We recently published the first rodent saliva proteomes with saliva collected from the genome mouse (C57BL/6 and the genome rat (BN/SsNHsd/Mcwi. Our second objective was to compare the proteins in the human proteome with those we identified in the genome mouse and rat to determine those common to all three mammals, as well as the specialized rodent subset. We also identified proteins unique to each of the three mammals, because differences in the secreted protein constitutions can provide clues to differences in the evolutionary adaptation of the secretions in the three different mammals.

Transcriptome of interstitial cells of Cajal reveals unique and selective gene signatures.

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Moon Young Lee

Full Text Available Transcriptome-scale data can reveal essential clues into understanding the underlying molecular mechanisms behind specific cellular functions and biological processes. Transcriptomics is a continually growing field of research utilized in biomarker discovery. The transcriptomic profile of interstitial cells of Cajal (ICC, which serve as slow-wave electrical pacemakers for gastrointestinal (GI smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow cytometry, we isolated ICC populations from the murine small intestine and colon and obtained their transcriptomes. In analyzing the transcriptome, we identified a unique set of ICC-restricted markers including transcription factors, epigenetic enzymes/regulators, growth factors, receptors, protein kinases/phosphatases, and ion channels/transporters. This analysis provides new and unique insights into the cellular and biological functions of ICC in GI physiology. Additionally, we constructed an interactive ICC genome browser (http://med.unr.edu/physio/transcriptome based on the UCSC genome database. To our knowledge, this is the first online resource that provides a comprehensive library of all known genetic transcripts expressed in primary ICC. Our genome browser offers a new perspective into the alternative expression of genes in ICC and provides a valuable reference for future functional studies.

What's So Special about FGF19-Unique Effects Reported on Skeletal Muscle Mass and Function.

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Glass, David J

2017-08-01

In a recent study published in Nature Medicine, Benoit et al. (2017) reported unique effects of FGF19 on mouse skeletal muscle: FGF19 induced skeletal muscle hypertrophy and blocked muscle atrophy, acting via FGF receptors and ßKlotho, while a related FGF21 hormone was ineffective. Copyright © 2017 Elsevier Inc. All rights reserved.

Modularity, comparative cognition and human uniqueness.

Science.gov (United States)

Shettleworth, Sara J

2012-10-05

Darwin's claim 'that the difference in mind between man and the higher animals … is certainly one of degree and not of kind' is at the core of the comparative study of cognition. Recent research provides unprecedented support for Darwin's claim as well as new reasons to question it, stimulating new theories of human cognitive uniqueness. This article compares and evaluates approaches to such theories. Some prominent theories propose sweeping domain-general characterizations of the difference in cognitive capabilities and/or mechanisms between adult humans and other animals. Dual-process theories for some cognitive domains propose that adult human cognition shares simple basic processes with that of other animals while additionally including slower-developing and more explicit uniquely human processes. These theories are consistent with a modular account of cognition and the 'core knowledge' account of children's cognitive development. A complementary proposal is that human infants have unique social and/or cognitive adaptations for uniquely human learning. A view of human cognitive architecture as a mosaic of unique and species-general modular and domain-general processes together with a focus on uniquely human developmental mechanisms is consistent with modern evolutionary-developmental biology and suggests new questions for comparative research.

The unique fold and lability of the [2Fe-2S] clusters of NEET proteins mediate their key functions in health and disease.

Science.gov (United States)

Karmi, Ola; Marjault, Henri-Baptiste; Pesce, Luca; Carloni, Paolo; Onuchic, Jose' N; Jennings, Patricia A; Mittler, Ron; Nechushtai, Rachel

2018-02-12

NEET proteins comprise a new class of [2Fe-2S] cluster proteins. In human, three genes encode for NEET proteins: cisd1 encodes mitoNEET (mNT), cisd2 encodes the Nutrient-deprivation autophagy factor-1 (NAF-1) and cisd3 encodes MiNT (Miner2). These recently discovered proteins play key roles in many processes related to normal metabolism and disease. Indeed, NEET proteins are involved in iron, Fe-S, and reactive oxygen homeostasis in cells and play an important role in regulating apoptosis and autophagy. mNT and NAF-1 are homodimeric and reside on the outer mitochondrial membrane. NAF-1 also resides in the membranes of the ER associated mitochondrial membranes (MAM) and the ER. MiNT is a monomer with distinct asymmetry in the molecular surfaces surrounding the clusters. Unlike its paralogs mNT and NAF-1, it resides within the mitochondria. NAF-1 and mNT share similar backbone folds to the plant homodimeric NEET protein (At-NEET), while MiNT's backbone fold resembles a bacterial MiNT protein. Despite the variation of amino acid composition among these proteins, all NEET proteins retained their unique CDGSH domain harboring their unique 3Cys:1His [2Fe-2S] cluster coordination through evolution. The coordinating exposed His was shown to convey the lability to the NEET proteins' [2Fe-2S] clusters. In this minireview, we discuss the NEET fold and its structural elements. Special attention is given to the unique lability of the NEETs' [2Fe-2S] cluster and the implication of the latter to the NEET proteins' cellular and systemic function in health and disease.

How calcium makes endocytic receptors attractive

DEFF Research Database (Denmark)

Andersen, Christian B F; Moestrup, Søren K

2014-01-01

of the receptor. Endosomal acidification and calcium efflux lead to the essential ligand-receptor affinity switch and separation. Recent data, including crystal structures of receptor-ligand complexes, now reveal how calcium, in different types of domain scaffolds, functions in a common way as a removable...... 'lynchpin' that stabilizes favorable positioning of ligand-attractive receptor residues. In addition to explaining how calcium depletion can cause ligand-receptor dissociation, the new data add further insight into how acidification contributes to dissociation through structural changes that affect...... the receptor calcium sites....

Putative and unique gene sequence utilization for the design of species specific probes as modeled by Lactobacillus plantarum

Science.gov (United States)

The concept of utilizing putative and unique gene sequences for the design of species specific probes was tested. The abundance profile of assigned functions within the Lactobacillus plantarum genome was used for the identification of the putative and unique gene sequence, csh. The targeted gene (cs...

Questions of uniqueness and resolution in reconstruction from projections

CERN Document Server

Katz, Myron Bernard

1978-01-01

Reconstruction from projections has revolutionized radiology and as now become one of the most important tools of medical diagnosi- he E. M. I. Scanner is one example. In this text, some fundamental heoretical and practical questions are resolved. Despite recent research activity in the area, the crucial subject ·f the uniqueness of the reconstruction and the effect of noise in the ata posed some unsettled fundamental questions. In particular, Kennan mith proved that if we describe an object by a C~ function, i. e. , nfinitely differentiable with compact support, then there are other bjects with the same shape, i. e. , support, which can differ almost rhitrarily and still have the same projections in finitely many direc­ ions. On the other hand, he proved that objects in finite dimensional unction spaces are uniquely determined by a single projection for almost 11 angles, i. e. , except on a set of measure zero. Along these lines, erman and Rowland in [41) showed that reconstructions obtained from he common...

Unique insula subregion resting-state functional connectivity with amygdala complexes in posttraumatic stress disorder and its dissociative subtype.

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Nicholson, Andrew A; Sapru, Iman; Densmore, Maria; Frewen, Paul A; Neufeld, Richard W J; Théberge, Jean; McKinnon, Margaret C; Lanius, Ruth A

2016-04-30

The insula and amygdala are implicated in the pathophysiology of posttraumatic stress disorder (PTSD), where both have been shown to be hyper/hypoactive in non-dissociative (PTSD-DS) and dissociative subtype (PTSD+DS) PTSD patients, respectively, during symptom provocation. However, the functional connectivity between individual insula subregions and the amygdala has not been investigated in persons with PTSD, with or without the dissociative subtype. We examined insula subregion (anterior, mid, and posterior) functional connectivity with the bilateral amygdala using a region-of-interest seed-based approach via PickAtlas and SPM8. Resting-state fMRI was conducted with (n=61) PTSD patients (n=44 PTSD-DS; n=17 PTSD+DS), and (n=40) age-matched healthy controls. When compared to controls, the PTSD-DS group displayed increased insula connectivity (bilateral anterior, bilateral mid, and left posterior) to basolateral amygdala clusters in both hemispheres, and the PTSD+DS group displayed increased insula connectivity (bilateral anterior, left mid, and left posterior) to the left basolateral amygdala complex. Moreover, as compared to PTSD-DS, increased insula subregion connectivity (bilateral anterior, left mid, and right posterior) to the left basolateral amygdala was found in PTSD+DS. Depersonalization/derealization symptoms and PTSD symptom severity correlated with insula subregion connectivity to the basolateral amygdala within PTSD patients. This study is an important first step in elucidating patterns of neural connectivity associated with unique symptoms of arousal/interoception, emotional processing, and awareness of bodily states, in PTSD and its dissociative subtype. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Amiloride-enhanced gene transfection of octa-arginine functionalized calcium phosphate nanoparticles.

Directory of Open Access Journals (Sweden)

Juan Ramón Vanegas Sáenz

Full Text Available Nanoparticles represent promising gene delivery systems in biomedicine to facilitate prolonged gene expression with low toxicity compared to viral vectors. Specifically, nanoparticles of calcium phosphate (nCaP, the main inorganic component of human bone, exhibit high biocompatibility and good biodegradability and have been reported to have high affinity for protein or DNA, having thus been used as gene transfer vectors. On the other hand, Octa-arginine (R8, which has a high permeability to cell membrane, has been reported to improve intracellular delivery systems. Here, we present an optimized method for nCaP-mediated gene delivery using an octa-arginine (R8-functionalized nCaP vector containing a marker or functional gene construct. nCaP particle size was between 220-580 nm in diameter and all R8-functionalized nCaPs carried a positive charge. R8 concentration significantly improved nCaP transfection efficiency with high cell compatibility in human mesenchymal stem cells (hMSC and human osteoblasts (hOB in particular, suggesting nCaPs as a good option for non-viral vector gene delivery. Furthermore, pre-treatment with different endocytosis inhibitors identified that the endocytic pathway differed among cell lines and functionalized nanoparticles, with amiloride increasing transfection efficiency of R8-functionalized nCaPs in hMSC and hOB.

Triazole: a unique building block for the construction of functional materials.

Science.gov (United States)

Juríček, Michal; Kouwer, Paul H J; Rowan, Alan E

2011-08-21

Over the past 50 years, numerous roads towards carbon-based materials have been explored, all of them being paved using mainly one functional group as the brick: acetylene. The acetylene group, or the carbon-carbon triple bond, is one of the oldest and simplest functional groups in chemistry, and although not present in any of the naturally occurring carbon allotropes, it is an essential tool to access their synthetic carbon-rich family. In general, two strategies towards the synthesis of π-conjugated carbon-rich structures can be employed: (a) either the acetylene group serves as a building block to access acetylene-derived structures or (b) it serves as a synthetic tool to provide other, usually benzenoid, structures. The recently discovered copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction, however, represents a new powerful alternative: it transforms the acetylene group into a five-membered heteroaromatic 1H-1,2,3-triazole (triazole) ring and this gives rise to new opportunities. Compared with all-carbon aromatic non-functional rings, the triazole ring possesses three nitrogen atoms and, thus, can serve as a ligand to coordinate metals, or as a hydrogen bond acceptor and donor. This Feature Article summarises examples of using the triazole ring to construct conjugation- and/or function-related heteroaromatic materials, such as tuneable multichromophoric covalent ensembles, macrocyclic receptors or responsive foldamers. These recent examples, which open a new sub-field within organic materials, started to appear only few years ago and represent "a few more bricks" on the road to carbon-rich functional materials. This journal is © The Royal Society of Chemistry 2011

The method of selecting an integrated development territory for the high-rise unique constructions

Science.gov (United States)

Sheina, Svetlana; Shevtsova, Elina; Sukhinin, Alexander; Priss, Elena

2018-03-01

On the basis of data provided by the Department of architecture and urban planning of the city of Rostov-on-don, the problem of the choice of the territory for complex development that will be in priority for the construction of high-rise and unique buildings is solved. The objective of the study was the development of a methodology for selection of the area and the implementation of the proposed method on the example of evaluation of four-territories complex development. The developed method along with standard indicators of complex evaluation considers additional indicators that assess the territory from the position of high-rise unique building. The final result of the study is the rankings of the functional priority areas that takes into account the construction of both residential and public and business objects of unique high-rise construction. The use of the developed methodology will allow investors and customers to assess the investment attractiveness of the future unique construction project on the proposed site.

Unique Reversible Crystal-to-Crystal Phase Transition – Structural and Functional Properties of Fused Ladder Thienoarenes

KAUST Repository

Abe, Yuichiro

2017-08-15

Donor-acceptor type molecules based on fused ladder thienoarenes, indacenodithiophene (IDT) and dithienocyclopenta-thienothiophene (DTCTT), coupled with benzothiadiazole, are prepared and their solid-state structures are investigated. They display a rich variety of solid phases ranging from amorphous glass states to crystalline states, upon changes in the central aromatic core and side group structures. Most notably, the DTCTT-based derivatives showed reversible crystal-to-crystal phase transitions in heating and cooling cycles. Unlike what has been seen in π−conjugated molecules variable temperature XRD revealed that structural change occurs continuously during the transition. A columnar self-assembled structure with slip-stacked π−π interaction is proposed to be involved in the solid-state. This research provides the evidence of unique structural behavior of the DTCTT-based molecules through the detailed structural analysis. This unique structural transition paves the way for these materials to have self-healing of crystal defects, leading to improved optoelectronic properties.

Unique Reversible Crystal-to-Crystal Phase Transition – Structural and Functional Properties of Fused Ladder Thienoarenes

KAUST Repository

Abe, Yuichiro; Savikhin, Victoria; Yin, Jun; Grimsdale, Andrew C.; Soci, Cesare; Toney, Michael F.; Lam, Yeng Ming

2017-01-01

Donor-acceptor type molecules based on fused ladder thienoarenes, indacenodithiophene (IDT) and dithienocyclopenta-thienothiophene (DTCTT), coupled with benzothiadiazole, are prepared and their solid-state structures are investigated. They display a rich variety of solid phases ranging from amorphous glass states to crystalline states, upon changes in the central aromatic core and side group structures. Most notably, the DTCTT-based derivatives showed reversible crystal-to-crystal phase transitions in heating and cooling cycles. Unlike what has been seen in π−conjugated molecules variable temperature XRD revealed that structural change occurs continuously during the transition. A columnar self-assembled structure with slip-stacked π−π interaction is proposed to be involved in the solid-state. This research provides the evidence of unique structural behavior of the DTCTT-based molecules through the detailed structural analysis. This unique structural transition paves the way for these materials to have self-healing of crystal defects, leading to improved optoelectronic properties.

Computational topology and the Unique Games Conjecture

OpenAIRE

Grochow, Joshua A.; Tucker-Foltz, Jamie

2018-01-01

Covering spaces of graphs have long been useful for studying expanders (as "graph lifts") and unique games (as the "label-extended graph"). In this paper we advocate for the thesis that there is a much deeper relationship between computational topology and the Unique Games Conjecture. Our starting point is Linial's 2005 observation that the only known problems whose inapproximability is equivalent to the Unique Games Conjecture - Unique Games and Max-2Lin - are instances of Maximum Section of...

The unique hemoglobin system of Pleuragramma antarcticum, an antarctic migratory teleost. Structure and function of the three components.

Science.gov (United States)

Tamburrini, M; D'Avino, R; Fago, A; Carratore, V; Kunzmann, A; Prisco, G

1996-09-27

Pleuragramma antarcticum (suborder Notothenioidei, family Nototheniidae) is the most abundant fish in the antarctic shelf. This pelagic species has a circum-antarctic distribution and is characterized by spawning migration. This species displays the highest multiplicity of major hemoglobins (three); the other notothenioids have a single one (except one species, having two) with relatively low oxygen affinity regulated by pH and organophosphates. The hemoglobins of P. antarcticum display strong Bohr and Root effects; however, they reveal important functional differences in subunit cooperativity and organophosphate regulation and, above all, in the response of oxygenation to temperature. Despite the substitution ValbetaE11 --> Ile found in Hb 2, which decreases the affinity in human mutants, the hemoglobins have similar oxygen affinity, higher than that of the other notothenioids. Hb 1 has the alpha chain in common with Hb 2 and the beta in common with Hb 3. The amino acid sequence of all four chains has been established. Thus the hematological features of P. antarcticum differ remarkably from those of antarctic notothenioids. This unique and sophisticated oxygen transport system may adequately meet the requirements of the unusual mode of life of this fish.

Unique expression of cytoskeletal proteins in human soft palate muscles.

Science.gov (United States)

Shah, Farhan; Berggren, Diana; Holmlund, Thorbjörn; Levring Jäghagen, Eva; Stål, Per

2016-03-01

The human oropharyngeal muscles have a unique anatomy with diverse and intricate functions. To investigate if this specialization is also reflected in the cytoarchitecture of muscle fibers, intermediate filament proteins and the dystrophin-associated protein complex have been analyzed in two human palate muscles, musculus uvula (UV) and musculus palatopharyngeus (PP), with immunohistochenmical and morphological techniques. Human limb muscles were used as reference. The findings show that the soft palate muscle fibers have a cytoskeletal architecture that differs from the limb muscles. While all limb muscles showed immunoreaction for a panel of antibodies directed against different domains of cytoskeletal proteins desmin and dystrophin, a subpopulation of palate muscle fibers lacked or had a faint immunoreaction for desmin (UV 11.7% and PP 9.8%) and the C-terminal of the dystrophin molecule (UV 4.2% and PP 6.4%). The vast majority of these fibers expressed slow contractile protein myosin heavy chain I. Furthermore, an unusual staining pattern was also observed in these fibers for β-dystroglycan, caveolin-3 and neuronal nitric oxide synthase nNOS, which are all membrane-linking proteins associated with the dystrophin C-terminus. While the immunoreaction for nNOS was generally weak or absent, β-dystroglycan and caveolin-3 showed a stronger immunostaining. The absence or a low expression of cytoskeletal proteins otherwise considered ubiquitous and important for integration and contraction of muscle cells indicate a unique cytoarchitecture designed to meet the intricate demands of the upper airway muscles. It can be concluded that a subgroup of muscle fibers in the human soft palate appears to have special biomechanical properties, and their unique cytoarchitecture must be taken into account while assessing function and pathology in oropharyngeal muscles. © 2015 Anatomical Society.

What is IgG4? A review of the biology of a unique immunoglobulin subtype.

Science.gov (United States)

Nirula, Ajay; Glaser, Scott M; Kalled, Susan L; Taylor, Frederick R; Taylora, Frederick R

2011-01-01

Recent descriptions of the group of clinical disorders collectively defined as IgG4-related systemic disease (IgG4-RSD) have prompted this review of the unique biology of the IgG4 antibody. This article will discuss IgG4 structure and function, the unique phenomenon of half-antibody exchange, and the implications of IgG4 biology for its proposed role in immunologic diseases. IgG4 antibodies have unique structural and functional properties and undergo 'half-antibody exchange' in vivo, resulting in recombined antibodies composed of two different binding specificities. The production of IgG4 antibodies appears to be driven in part by T helper 2 (Th2) cytokines that mediate allergic responses and IgE production. Although serum IgG4 levels in healthy individuals vary significantly, data from multiple sclerosis (MS) patients suggest tight regulation of individual IgG4 levels over time. IgG4-RSD represents a diverse group of clinical disorders unified by elevated IgG4 levels and specific histopathologic findings. A key unanswered question is whether IgG4, a relatively weak activator of effector cells, is pathogenic in these disorders. IgG4 is a unique antibody biologically and structurally. Increased understanding of its precise role in the clinical syndromes that comprise IgG4-RSD may ultimately elucidate the underlying pathogenesis.

Unique Action of Interleukin-18 on T Cells and Other Immune Cells

Directory of Open Access Journals (Sweden)

Kenji Nakanishi

2018-04-01

Full Text Available Interleukin (IL-18 was originally discovered as a factor that enhances interferon (IFN-γ production by anti-CD3-stimulated Th1 cells, particularly in association with IL-12. IL-12 is a cytokine that induces development of Th1 cells. IL-18 cannot induce Th1 cell development, but has the capacity to activate established Th1 cells to produce IFN-γ in the presence of IL-12. Thus, IL-18 is regarded as a proinflammatory cytokine that facilitates type 1 responses. However, in the absence of IL-12 but presence of IL-2, IL-18 stimulates natural killer cells, NKT cells, and even established Th1 cells to produce IL-3, IL-9, and IL-13. Thus, IL-18 also facilitates type 2 responses. This unique function of IL-18 contributes to infection-associated allergic diseases. Together with IL-3, IL-18 stimulates mast cells and basophils to produce IL-4, IL-13, and chemical mediators such as histamine. Thus, IL-18 also induces innate-type allergic inflammation. IL-18 belongs to the IL-1 family of cytokines, which share similar molecular structures, receptors structures, and signal transduction pathways. Nevertheless, IL-18 shows a unique function by binding to a specific receptor expressed on distinct types of cells. In this review article, I will focus on the unique features of IL-18 in lymphocytes, basophils, and mast cells, particularly in comparison with IL-33.

Novel functions for the endocytic regulatory proteins MICAL-L1 and EHD1 in mitosis.

Science.gov (United States)

Reinecke, James B; Katafiasz, Dawn; Naslavsky, Naava; Caplan, Steve

2015-01-01

During interphase, recycling endosomes mediate the transport of internalized cargo back to the plasma membrane. However, in mitotic cells, recycling endosomes are essential for the completion of cytokinesis, the last phase of mitosis that promotes the physical separation the two daughter cells. Despite recent advances, our understanding of the molecular determinants that regulate recycling endosome dynamics during cytokinesis remains incomplete. We have previously demonstrated that Molecule Interacting with CasL Like-1 (MICAL-L1) and C-terminal Eps15 Homology Domain protein 1 (EHD1) coordinately regulate receptor transport from tubular recycling endosomes during interphase. However, their potential roles in controlling cytokinesis had not been addressed. In this study, we show that MICAL-L1 and EHD1 regulate mitosis. Depletion of either protein resulted in increased numbers of bi-nucleated cells. We provide evidence that bi-nucleation in MICAL-L1- and EHD1-depleted cells is a consequence of impaired recycling endosome transport during late cytokinesis. However, depletion of MICAL-L1, but not EHD1, resulted in aberrant chromosome alignment and lagging chromosomes, suggesting an EHD1-independent function for MICAL-L1 earlier in mitosis. Moreover, we provide evidence that MICAL-L1 and EHD1 differentially influence microtubule dynamics during early and late mitosis. Collectively, our new data suggest several unanticipated roles for MICAL-L1 and EHD1 during the cell cycle. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

"That thing in New York": Impaired naming vs. preserved recognition of unique entities following an anterior temporal lobe lesion

Directory of Open Access Journals (Sweden)

Daniel Roberts

2014-04-01

Full Text Available Background Anterior temporal lobe (aTL damage often results in semantic impairment. As such, the contribution of this region to semantic processing has received considerable attention. Two theories exist to explain aTL function based on conflicting neuropsychological investigations. The first proposes bilateral aTLs form a “hub” implicated in multimodal semantics (for review see: Jefferies, 2013. The second assumes distinct functions. The left is thought to function as a repertoire for knowledge of entities with unique lexical-conceptual associations (for review: Ross & Olson, 2012. These items represent an extreme end of a continuum of semantic specificity spanning unique (e.g., Eiffel Tower over less specific (e.g., tower to nonspecific (e.g., landmark – often denoted by famous faces, landmarks and proper names. LaTL function, therefore, is to link semantics to language systems for naming, whilst RaTL is involved in familiarity and recognition (e.g., Eiffel Tower -> a building in Paris; Drane et al., 2013. Evidence for each theory has proceeded in parallel but there has been no attempt to directly test them in a patient (Simmons & Martin, 2009. The novelty of this study, therefore, was to determine whether LaTL lesions disproportionately affect unique entity naming vs. recognition. Method WRP, a 51year old right-handed male, three year post-HSVE has a LaTL lesion with destruction of the temporal pole, extending to medial temporal, amygdala and hippocampus and atypical connectivity particularly involving the uncinate fasciculas. There is no evidence of either cortical or white matter damage in the right hemisphere. Previous work with WRP revealed a mild/moderate category-specific semantic deficit (Roberts et al., 2012. This new study focuses on unique entity picture naming, recognition and word-to-picture matching (WPM. Results & Discussion As predicted, results (Table 1 show that WRP was severely impaired in naming different categories

Heart Failure: Unique to Older Adults

Science.gov (United States)

... to Z › Heart Failure › Unique to Older Adults Font size A A A Print Share Glossary Unique ... will suffer from depression at some point. This type of severe depression is more serious than the ...

Unique Turbinal Morphology in Horseshoe Bats (Chiroptera: Rhinolophidae).

Science.gov (United States)

Curtis, Abigail A; Simmons, Nancy B

2017-02-01

The mammalian nasal fossa contains a set of delicate and often structurally complex bones called turbinals. Turbinals and associated mucosae function in regulating respiratory heat and water loss, increasing surface area for olfactory tissue, and directing airflow within the nasal fossa. We used high-resolution micro-CT scanning to investigate a unique maxilloturbinal morphology in 37 species from the bat family Rhinolophidae, which we compared with those of families Hipposideridae, Megadermatidae, and Pteropodidae. Rhinolophids exhibit numerous structural modifications along the nasopharyngeal tract associated with emission of high duty cycle echolocation calls via the nostrils. In rhinolophids, we found that the maxilloturbinals and a portion of ethmoturbinal I form a pair of strand-like bony structures on each side of the nasal chamber. These structures project anteriorly from the transverse lamina and complete a hairpin turn to project posteriorly down the nasopharyngeal duct, and vary in length among species. The strand-like maxilloturbinals in Rhinolophidae were not observed in our outgroups and represent a synapomorphy for this family, and are unique in form among mammals. Within Rhinolophidae, maxilloturbinal size and cross-sectional shape were correlated with phylogeny. We hypothesize that strand-shaped maxilloturbinals may function to reduce respiratory heat and water loss without greatly impacting echolocation call transmission since they provide increased mucosal surface area for heat and moisture exchange but occupy minimal space. Alternatively, they may play a role in transmission of echolocation calls since they are located directly along the path sound travels between the larynx and nostrils during call emission. Anat Rec, 300:309-325, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Existence and Uniqueness of Solutions to the Stochastic Porous Media Equations of Saturated Flows

International Nuclear Information System (INIS)

Ciotir, Ioana

2010-01-01

This paper proves the existence and uniqueness of nonnegative solutions for the stochastic porous media equations with multiplicative noise, infinite jump and discontinuous diffusivity function relevant in description of saturation processes in underground water infiltration in a bounded domain of R 3 .

The method of selecting an integrated development territory for the high-rise unique constructions

Directory of Open Access Journals (Sweden)

Sheina Svetlana

2018-01-01

Full Text Available On the basis of data provided by the Department of architecture and urban planning of the city of Rostov-on-don, the problem of the choice of the territory for complex development that will be in priority for the construction of high-rise and unique buildings is solved. The objective of the study was the development of a methodology for selection of the area and the implementation of the proposed method on the example of evaluation of four-territories complex development. The developed method along with standard indicators of complex evaluation considers additional indicators that assess the territory from the position of high-rise unique building. The final result of the study is the rankings of the functional priority areas that takes into account the construction of both residential and public and business objects of unique high-rise construction. The use of the developed methodology will allow investors and customers to assess the investment attractiveness of the future unique construction project on the proposed site.

EXISTENCE AND UNIQUENESS OF THE ENTROPY SOLUTION TO A NONLINEAR HYPERBOLIC EQUATION

Institute of Scientific and Technical Information of China (English)

R.EYMARD; T.Gallouёt; R.Herbin

1995-01-01

This work is concerned with the proof of the existence and uniqueness of the entropy weak solution to the following nonlinear hyperbolic equation: ut+div(vf(u)） = 0 in IRN×（0, T）, with initial data u(-, 0) = u0(-) in IRN, where u0 ∈ L∞（IRN) is a given function, v is a divergence-free bounded fnnction of class C1 from IRN × [0, T] to IRN, and f is a 5motion of class C1 from IR to IR. It also gives a result of convergence of a numerical scheme for the discretization of this equation. The authors first show the existence of a “process” solution (which generalizes the concept of entropy weak solutions, and can be obtained by passing to the limit of solutions ofthe numerical scheme). The uniqueness of this entropy process solution is then proven; it isalso proven that the entropy process solution is in fact an entropy weak solution. Hence the existence and uniqueness of the entropy weak solution are proven.

Uniqueness theorems for variational problems by the method of transformation groups

CERN Document Server

Reichel, Wolfgang

2004-01-01

A classical problem in the calculus of variations is the investigation of critical points of functionals {\\cal L} on normed spaces V. The present work addresses the question: Under what conditions on the functional {\\cal L} and the underlying space V does {\\cal L} have at most one critical point? A sufficient condition for uniqueness is given: the presence of a "variational sub-symmetry", i.e., a one-parameter group G of transformations of V, which strictly reduces the values of {\\cal L}. The "method of transformation groups" is applied to second-order elliptic boundary value problems on Riemannian manifolds. Further applications include problems of geometric analysis and elasticity.

Unitary evolution and uniqueness of the Fock quantization in flat cosmologies

International Nuclear Information System (INIS)

Marugán, G A Mena; Błas, D Martín-de; Gomar, L Castelló

2013-01-01

We study the Fock quantization of scalar fields with a time dependent mass in cosmological scenarios with flat compact spatial sections. This framework describes physically interesting situations like, e.g., cosmological perturbations in flat Friedmann-Robertson-Walker spacetimes, generally including a suitable scaling of them by a background function. We prove that the requirements of vacuum invariance under the spatial isometries and of a unitary quantum dynamics select (a) a unique canonical pair of field variables among all those related by time dependent canonical transformations which scale the field configurations, and (b) a unique Fock representation for the canonical commutation relations of this pair of variables. The proof is generalizable to any compact spatial topology in three or less dimensions, though we focus on the case of the three-torus owing to the especially relevant implications.

Unique specification of Yang-Mills solutions

International Nuclear Information System (INIS)

Campbell, W.B.; Joseph, D.W.; Morgan, T.A.

1980-01-01

Screened time-independent cylindrically-symmetric solutions of Yang-Mills equations are given which show that the source does not uniquely determine the field. However, these particular solutions suggest a natural way of uniquely specifying solutions in terms of a physical realization of a symmetry group. (orig.)

Exact criteria for uniqueness and multiplicity of an nth order chemical reaction via catastrophe theory approach. [Determines boundaries between unique and multiple steady state conditions

Energy Technology Data Exchange (ETDEWEB)

Chang, H C; Calo, J M

1979-01-01

A simple, generalized technique for the exact determination of the boundaries between regions of unique and of multiple solutions to certain nonlinear equations was developed by applying catastrophe theory to the mapping of implicit and explicit functions. Its application to an nth order reaction in continuous stirred tank reactor (CSTR) yields exact, explicit expressions for the boundaries between regions of single and multiple steady states, expressed in terms of the dimensionless heat transfer coefficient and activation energy. An exact implicit expression for the boundaries between regions of uniqueness and multiplicity was also derived for an nth order reaction in a catalyst particle with an intraparticle concentration gradient and uniform temperature and is fully demonstrated for the first-order reaction. In addition, explicit criteria were developed by assuming the limits on d ln g/d ln q, where g is the effectiveness factor and q the Thiele modulus, proposed by van den Bosch and Luss.

Multivesicular Bodies in Neurons: Distribution, Protein Content, and Trafficking Functions

Science.gov (United States)

VON BARTHELD, CHRISTOPHER S.; ALTICK, AMY L.

2011-01-01

Summary Multivesicular bodies (MVBs) are intracellular endosomal organelles characterized by multiple internal vesicles that are enclosed within a single outer membrane. MVBs were initially regarded as purely prelysosomal structures along the degradative endosomal pathway of internalized proteins. MVBs are now known to be involved in numerous endocytic and trafficking functions, including protein sorting, recycling, transport, storage, and release. This review of neuronal MVBs summarizes their research history, morphology, distribution, accumulation of cargo and constitutive proteins, transport, and theories of functions of MVBs in neurons and glia. Due to their complex morphologies, neurons have expanded trafficking and signaling needs, beyond those of “geometrically simpler” cells, but it is not known whether neuronal MVBs perform additional transport and signaling functions. This review examines the concept of compartment-specific MVB functions in endosomal protein trafficking and signaling within synapses, axons, dendrites and cell bodies. We critically evaluate reports of the accumulation of neuronal MVBs based on evidence of stress-induced MVB formation. Furthermore, we discuss potential functions of neuronal and glial MVBs in development, in dystrophic neuritic syndromes, injury, disease, and aging. MVBs may play a role in Alzheimer’s, Huntington’s, and Niemann-Pick diseases, some types of frontotemporal dementia, prion and virus trafficking, as well as in adaptive responses of neurons to trauma and toxin or drug exposure. Functions of MVBs in neurons have been much neglected, and major gaps in knowledge currently exist. Developing truly MVB-specific markers would help to elucidate the roles of neuronal MVBs in intra- and intercellular signaling of normal and diseased neurons. PMID:21216273

Roles of AP-2 in clathrin-mediated endocytosis.

Directory of Open Access Journals (Sweden)

Emmanuel Boucrot

2010-05-01

Full Text Available The notion that AP-2 clathrin adaptor is an essential component of an endocytic clathrin coat appears to conflict with recent observations that substantial AP-2 depletion, using RNA interference with synthesis of AP-2 subunits, fails to block uptake of certain ligands known to internalize through a clathrin-based pathway.We report here the use of in vivo imaging data obtained by spinning-disk confocal microscopy to study the formation of clathrin-coated structures at the plasma membranes of BSC1 and HeLa cells depleted by RNAi of the clathrin adaptor, AP-2. Very few clathrin coats continue to assemble after AP-2 knockdown. Moreover, there is a total absence of clathrin-containing structures completely lacking AP-2 while all the remaining coats still contain a small amount of AP-2. These observations suggest that AP-2 is essential for endocytic coated-pit and coated-vesicle formation. We also find that AP-2 knockdown strongly inhibits light-density lipoprotein (LDL receptor-mediated endocytosis, as long as cells are maintained in complete serum and at 37 degrees C. If cells are first incubated with LDL at 4 degrees C, followed by warming, there is little or no decrease in LDL uptake with respect to control cells. LDL uptake at 37 degrees C is also not affected in AP-2 depleted cells first deprived of LDL by incubation with either serum-starved or LDL-starved cells for 24 hr. The LDL-deprived cells display a significant increase in endocytic structures enriched on deeply invaginated tubes that contain LDL and we suggest that under this condition of stress, LDL might enter through this alternative pathway.These results suggest that AP-2 is essential for endocytic clathrin coated-pit and coated-vesicle formation. They also indicate that under normal conditions, functional endocytic clathrin coated pits are required for LDL internalization. We also show that under certain conditions of stress, cells can upregulate alternative endocytic structures

Uniqueness of time-independent electromagnetic fields

DEFF Research Database (Denmark)

Karlsson, Per W.

1974-01-01

As a comment on a recent paper by Steele, a more general uniqueness theorem for time-independent fields is mentioned. ©1974 American Institute of Physics......As a comment on a recent paper by Steele, a more general uniqueness theorem for time-independent fields is mentioned. ©1974 American Institute of Physics...

Changes in unique hues induced by chromatic surrounds.

Science.gov (United States)

Klauke, Susanne; Wachtler, Thomas

2016-03-01

A chromatic surround can have a strong influence on the perceived hue of a stimulus. We investigated whether chromatic induction has similar effects on the perception of colors that appear pure and unmixed (unique red, green, blue, and yellow) as on other colors. Subjects performed unique hue settings of stimuli in isoluminant surrounds of different chromaticities. Compared with the settings in a neutral gray surround, unique hue settings altered systematically with chromatic surrounds. The amount of induced hue shift depended on the difference between stimulus and surround hues, and was similar for unique hue settings as for settings of nonunique hues. Intraindividual variability in unique hue settings was roughly twice as high as for settings obtained in asymmetric matching experiments, which may reflect the presence of a reference stimulus in the matching task. Variabilities were also larger with chromatic surrounds than with neutral gray surrounds, for both unique hue settings and matching of nonunique hues. The results suggest that the neural representations underlying unique hue percepts are influenced by the same neural processing mechanisms as the percepts of other colors.

The Parkinson's disease-associated protein DJ-1 plays a positive nonmitochondrial role in endocytosis in Dictyostelium cells

Directory of Open Access Journals (Sweden)

Suwei Chen

2017-10-01

Full Text Available The loss of function of DJ-1 caused by mutations in DJ1 causes a form of familial Parkinson's disease (PD. However, the role of DJ-1 in healthy and in PD cells is poorly understood. Even its subcellular localization in mammalian cells is uncertain, with both cytosolic and mitochondrial locations having been reported. We show here that DJ-1 is normally located in the cytoplasm in healthy Dictyostelium discoideum cells. With its unique life cycle, straightforward genotype-phenotype relationships, experimental accessibility and genetic tractability, D. discoideum offers an attractive model to investigate the roles of PD-associated genes. Furthermore, the study of mitochondrial biology, mitochondrial genome transcription and AMP-activated protein kinase-mediated cytopathologies in mitochondrial dysfunction have been well developed in this organism. Unlike mammalian systems, Dictyostelium mitochondrial dysfunction causes a reproducible and readily assayed array of aberrant phenotypes: defective phototaxis, impaired growth, normal rates of endocytosis and characteristic defects in multicellular morphogenesis. This makes it possible to study whether the underlying cytopathological mechanisms of familial PD involve mitochondrial dysfunction. DJ-1 has a single homologue in the Dictyostelium genome. By regulating the expression level of DJ-1 in D. discoideum, we show here that in unstressed cells, DJ-1 is required for normal rates of endocytic nutrient uptake (phagocytosis and, to a lesser extent, pinocytosis and thus growth. Reduced expression of DJ-1 had no effect on phototaxis in the multicellular migratory ‘slug’ stage of the life cycle, but resulted in thickened stalks in the final fruiting bodies. This pattern of phenotypes is distinct from that observed in Dictyostelium to result from mitochondrial dyfunction. Direct measurement of mitochondrial respiratory function in intact cells revealed that DJ-1 knockdown stimulates whereas DJ-1

Characterization and endocytic internalization of Epith-2 cell surface glycoprotein during the epithelial-to-mesenchymal transition in sea urchin embryos

Directory of Open Access Journals (Sweden)

Norio eWakayama

2013-08-01

Full Text Available The epithelial cells of the sea urchin Hemicentrotus pulcherrimus embryo express an Epith-2, uncharacterized glycoprotein, on the lateral surface. Here, we describe internalization of Epith-2 during mesenchyme formation through the epithelial-to-mesenchymal transition (EMT. Epith-2 was first expressed on the entire egg surface soon after fertilization and on the blastomeres until the 4-cell stage, but was localized to the lateral surface of epithelial cells at and after the 16-cell stage throughout the later developmental period. However, primary (PMC and secondary mesenchyme cells (SMC that ingress by EMT lost Epith-2 from their cell surface by endocytosis during dissociation from the epithelium, which was associated with the appearance of cytoplasmic Epith-2 dots. The cytoplasmic Epith-2 retained a similar relative molecular mass to that of the cell surface immediately after ingression through the early period of the spreading to single cells. Then, Epith-2 was completely lost from the cytoplasm. Tyrosine residues of Epith-2 were phosphorylated. The endocytic retraction of Epith-2 was inhibited by herbimycin A (HA, a protein tyrosine kinase (PTK inhibitor, and suramin, a growth factor receptor (GFR inhibitor, suggesting the involvement of the GFR/PTK (GP signaling pathway. These two GP inhibitors also inhibited PMC and SMC spreading to individual cells after ingression, but the dissociation of PMC and SMC from the epithelium was not inhibited. In suramin-treated embryos, dissociated mesenchyme cells migrated partially by retaining their epithelial morphology. In HA-treated embryos, no mesenchyme cells migrated. Thus, the EMT occurs in relation to internalization of Epith-2 from presumptive PMC and SMC.

The liberal illusion of uniqueness.

Science.gov (United States)

Stern, Chadly; West, Tessa V; Schmitt, Peter G

2014-01-01

In two studies, we demonstrated that liberals underestimate their similarity to other liberals (i.e., display truly false uniqueness), whereas moderates and conservatives overestimate their similarity to other moderates and conservatives (i.e., display truly false consensus; Studies 1 and 2). We further demonstrated that a fundamental difference between liberals and conservatives in the motivation to feel unique explains this ideological distinction in the accuracy of estimating similarity (Study 2). Implications of the accuracy of consensus estimates for mobilizing liberal and conservative political movements are discussed.

Syndecans as cell surface receptors: Unique structure equates with functional diversity

DEFF Research Database (Denmark)

Choi, Youngsil; Chung, Heesung; Jung, Heyjung

2011-01-01

An increasing number of functions for syndecan cell surface heparan sulfate proteoglycans have been proposed over the last decade. Moreover, aberrant syndecan regulation has been found to play a critical role in multiple pathologies, including cancers, as well as wound healing and inflammation....... As receptors, they have much in common with other molecules on the cell surface. Syndecans are type I transmembrane molecules with cytoplasmic domains that link to the actin cytoskeleton and can interact with a number of regulators. However, they are also highly complex by virtue of their external...... glycosaminoglycan chains, especially heparan sulfate. This heterodisperse polysaccharide has the potential to interact with many ligands from diverse protein families. Here, we relate the structural features of syndecans to some of their known functions....

Biological functionalization of drug delivery carriers to bypass size restrictions of receptor-mediated endocytosis independently from receptor targeting.

Science.gov (United States)

Ansar, Maria; Serrano, Daniel; Papademetriou, Iason; Bhowmick, Tridib Kumar; Muro, Silvia

2013-12-23

Targeting of drug carriers to cell-surface receptors involved in endocytosis is commonly used for intracellular drug delivery. However, most endocytic receptors mediate uptake via clathrin or caveolar pathways associated with ≤200-nm vesicles, restricting carrier design. We recently showed that endocytosis mediated by intercellular adhesion molecule 1 (ICAM-1), which differs from clathrin- and caveolae-mediated pathways, allows uptake of nano- and microcarriers in cell culture and in vivo due to recruitment of cellular sphingomyelinases to the plasmalemma. This leads to ceramide generation at carrier binding sites and formation of actin stress-fibers, enabling engulfment and uptake of a wide size-range of carriers. Here we adapted this paradigm to enhance uptake of drug carriers targeted to receptors associated with size-restricted pathways. We coated sphingomyelinase onto model (polystyrene) submicro- and microcarriers targeted to clathrin-associated mannose-6-phosphate receptor. In endothelial cells, this provided ceramide enrichment at the cell surface and actin stress-fiber formation, modifying the uptake pathway and enhancing carrier endocytosis without affecting targeting, endosomal transport, cell-associated degradation, or cell viability. This improvement depended on the carrier size and enzyme dose, and similar results were observed for other receptors (transferrin receptor) and cell types (epithelial cells). This phenomenon also enhanced tissue accumulation of carriers after intravenous injection in mice. Hence, it is possible to maintain targeting toward a selected receptor while bypassing natural size restrictions of its associated endocytic route by functionalization of drug carriers with biological elements mimicking the ICAM-1 pathway. This strategy holds considerable promise to enhance flexibility of design of targeted drug delivery systems.

Generation of stable lipid raft microdomains in the enterocyte brush border by selective endocytic removal of non-raft membrane

DEFF Research Database (Denmark)

Danielsen, E Michael; Hansen, Gert H

2013-01-01

The small intestinal brush border has an unusually high proportion of glycolipids which promote the formation of lipid raft microdomains, stabilized by various cross-linking lectins. This unique membrane organization acts to provide physical and chemical stability to the membrane that faces...... functions to enrich the contents of lipid raft components in the brush border. The lipophilic fluorescent marker FM, taken up into early endosomes in the terminal web region (TWEEs), was absent from detergent resistant membranes (DRMs), implying an association with non-raft membrane. Furthermore, neither...... major lipid raft-associated brush border enzymes nor glycolipids were detected by immunofluorescence microscopy in subapical punctae resembling TWEEs. Finally, two model raft lipids, BODIPY-lactosylceramide and BODIPY-GM1, were not endocytosed except when cholera toxin subunit B (CTB) was present...

Uniqueness in some higher order elliptic boundary value problems in n dimensional domains

Directory of Open Access Journals (Sweden)

C.-P. Danet

2011-07-01

Full Text Available We develop maximum principles for several P functions which are defined on solutions to equations of fourth and sixth order (including a equation which arises in plate theory and bending of cylindrical shells. As a consequence, we obtain uniqueness results for fourth and sixth order boundary value problems in arbitrary n dimensional domains.

Structural and biochemical analysis of a unique phosphatase from Bdellovibrio bacteriovorus reveals its structural and functional relationship with the protein tyrosine phosphatase class of phytase.

Directory of Open Access Journals (Sweden)

Robert J Gruninger

Full Text Available Bdellovibrio bacteriovorus is an unusual δ-proteobacterium that invades and preys on other Gram-negative bacteria and is of potential interest as a whole cell therapeutic against pathogens of man, animals and crops. PTPs (protein tyrosine phosphatases are an important class of enzyme involved in desphosphorylating a variety of substrates, often with implications in cell signaling. The B. bacteriovorus open reading frame Bd1204 is predicted to encode a PTP of unknown function. Bd1204 is both structurally and mechanistically related to the PTP-like phytase (PTPLP class of enzymes and possesses a number of unique properties not observed in any other PTPLPs characterized to date. Bd1204 does not display catalytic activity against some common protein tyrosine phosphatase substrates but is highly specific for hydrolysis of phosphomonoester bonds of inositol hexakisphosphate. The structure reveals that Bd1204 has the smallest and least electropositive active site of all characterized PTPLPs to date yet possesses a unique substrate specificity characterized by a strict preference for inositol hexakisphosphate. These two active site features are believed to be the most significant contributors to the specificity of phytate degrading enzymes. We speculate that Bd1204 may be involved in phosphate acquisition outside of prey.

Neuron specific Rab4 effector GRASP-1 coordinates membrane specialization and maturation of recycling endosomes

NARCIS (Netherlands)

C.C. Hoogenraad (Casper); I. Popa (Ioana); K. Futai (Kensuke); E. Sanchez-Martinez (Emma); P. Wulf (Phebe); T. van Vlijmen (Thijs); B.R. Dortland (Bjorn); V. Oorschot (Viola); R. Govers (Robert); M. Monti (Maria); A.J.R. Heck (Albert); M. Sheng (Morgan); J. Klumperman (Judith); H. Rehmann (Holger); D. Jaarsma (Dick); L.C. Kapitein (Lukas); P. van der Sluijs

2010-01-01

textabstractThe endosomal pathway in neuronal dendrites is essential for membrane receptor trafficking and proper synaptic function and plasticity. However, the molecular mechanisms that organize specific endocytic trafficking routes are poorly understood. Here, we identify GRIP-associated protein-1

Non-unique Product Groups on Two Generators

OpenAIRE

Carter, William Paul

2007-01-01

The main purpose of this paper is to better understand groups that do not have the unique product property. In particular, the goal is to better understand Promislow's example, G, of such a group. In doing so, we will develop methods for generating examples of other sets that do not have the unique product property. With these methods we can show that there exists other distinct 14 element, square, non-unique product sets in G that are not inversions or translations. Also, this paper answers ...

On a Functional Equation for the Generating Function of the Logarithmic Series Distribution

OpenAIRE

Panaretos, John

1987-01-01

This note deals with finding the solution of a functional equation, where the function involved has the additional property of being a probability generating function. It turns out that the unique solution of this particular functional equation is the probability generating function of the logarithmic series distribution

Phylogenetic and functional diversity of Bacteria and Archaea in a unique stratified lagoon, the Clipperton atoll (N Pacific).

Science.gov (United States)

Galand, Pierre E; Bourrain, Muriel; De Maistre, Emmanuel; Catala, Philippe; Desdevises, Yves; Elifantz, Hila; Kirchman, David L; Lebaron, Philippe

2012-01-01

The Clipperton lagoon in the North Pacific Ocean has been isolated from the surrounding sea for c. 160 years. It has a stratified water column that comprises an oxic and brackish upper water layer (mixolimnion) and a deep sulfuric anoxic saline layer (monimolimnion), separated by a steep pycnocline. Here, we test whether the Clipperton lagoon with its distinctive physico-chemical features, geographic isolation, recent water column stratification, and large nutrient input harbors original microbial communities. The combination of capillary electrophoresis single-strand polymorphism (CE-SSCP) fingerprinting and sequencing of cloned bacterial and archaeal 16S rRNA genes, and functional genes for methanogenesis (mcrA), methanotrophy (pmoA), and sulfate reduction (dsrAB), revealed that microbial communities and pathways were highly stratified down the water column. The mixolimnion contained ubiquitous freshwater clades of Alpha- and Betaproteobacteria, while the pycnocline contained mostly green sulfur bacteria (phylum Chlorobi). Sequences of the upper layers were closely related to sequences found in other aquatic ecosystems, suggesting that they have a strong potential for dispersal and colonization. In contrast, the monimolimnion contained new deeply branching bacterial divisions within the OP11 cluster and the Bacteroidetes, and was the most diverse of the layers. The unique environmental conditions characterizing the deep layers of the lagoon may explain the novelty of the microbial communities found at the Clipperton atoll.

Comparative Fecal Metagenomics Unveils Unique Functional Capacity of the Swine Gut

Science.gov (United States)

Uncovering the taxonomic composition and functional capacity within the swine gut microbial consortia is of great importance to animal physiology and health and to food and water safety due to the presence of human pathogens in pig feces. Limited information on the physiological...

Tattoos and piercings: bodily expressions of uniqueness?

Science.gov (United States)

Tiggemann, Marika; Hopkins, Louise A

2011-06-01

The study aimed to investigate the motivations underlying the body modification practices of tattooing and piercing. There were 80 participants recruited from an Australian music store, who provided descriptions of their tattoos and piercings and completed measures of need for uniqueness, appearance investment and distinctive appearance investment. It was found that tattooed individuals scored significantly higher on need for uniqueness than non-tattooed individuals. Further, individuals with conventional ear piercings scored significantly lower on need for uniqueness than individuals with no piercings or with facial and body piercings. Neither appearance investment nor distinctive appearance investment differed significantly among tattoo or piercing status groups. Strength of identification with music was significantly correlated with number of tattoos, but not number of piercings. It was concluded that tattooing, but not body piercing, represents a bodily expression of uniqueness. Copyright © 2011 Elsevier Ltd. All rights reserved.

The subapical compartment : a traffic center in membrane polarity development

NARCIS (Netherlands)

Hoekstra, D; Tyteca, D; van IJzendoorn, SCD

2004-01-01

Spatially separated apical and basolateral plasma membrane domains that have distinct functions and molecular compositions are a characteristic feature of epithelial cell polarity. The subapical compartment (SAC), also known as the common endosome (CE), where endocytic pathways from both surfaces

Analysis of the toxicity of gold nano particles on the immune system: effect on dendritic cell functions

International Nuclear Information System (INIS)

Villiers, Christian L.; Freitas, Heidi; Couderc, Rachel; Villiers, Marie-Bernadette; Marche, Patrice N.

2010-01-01

The effect of manufactured gold nanoparticles (NPs) on the immune system was analysed through their ability to perturb the functions of dendritic cells (DCs), a major actor of both innate and acquired immune responses. For this purpose, DCs were produced in culture from mouse bone marrow progenitors. The analysis of the viability of the cells after their incubation in the presence of gold NPs shows that these NPs are not cytotoxics even at high concentration. Furthermore, the phenotype of the DC is unchanged after the addition of NPs, indicating that there is no activation of the DC. However, the analysis of the cells at the intracellular level reveals important amounts of gold NPs amassing in endocytic compartments. Furthermore, the secretion of cytokines is significantly modified after such internalisation indicating a potential perturbation of the immune response.

Fiscal 1997 R and D project on industrial science and technology under a consignment from NEDO. R and D of the application technology of functional protein complex (R and D of the high-functional maintenance technology for power plants); 1997 nendo sangyo kagaku gijutsu kenkyu kaihatsu jigyo Shin energy Sangyo gijutsu Sogo Kaihatsu Kiko itaku. Kinosei tanpakushitsu shugotai oyo gijutsu no kenkyu kaihatsu (hatsuden shisetsuyo kokino maintenance gijutsu kaihatsu) seika hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-03-01

In order to develop advanced maintenance technology for power generation facilities, application technology of functional protein complexes is under investigation. On a light controllable enzymatic reaction system, construction of a light controllable bio-reactor by physico-chemical and bio- chemical techniques, and structure and functions of a photosynthetic protein complex using thermophilic cyanobacteria as material are under investigation. On a molecular mechanism for recognition and reaction of receptor proteins, structure analysis and engineering application of glutamate receptor channels of a synaptic transmission system, and basic study and material proteins for artificial structures using endocytic micromachinery, and a multi-enzyme system for synthesis of glycosphingolipids are under investigation. On a complex oxidation/reduction system by genetic engineering technique, construction of a high- efficiency stable system with functionally arranged oxidoreductase and electron transmission systems in biomembranes is in promotion. Research work was also made on molecular assemblies for a functional protein system. 166 refs., 91 figs., 9 tabs.

Uniqueness conditions for finitely dependent random fields

International Nuclear Information System (INIS)

Dobrushin, R.L.; Pecherski, E.A.

1981-01-01

The authors consider a random field for which uniqueness and some additional conditions guaranteeing that the correlations between the variables of the field decrease rapidly enough with the distance between the values of the parameter occur. The main result of the paper states that in such a case uniqueness is true for any other field with transition probabilities sufficiently close to those of the original field. Then they apply this result to some ''degenerate'' classes of random fields for which one can check this condition of correlation to decay, and thus obtain some new conditions of uniqueness. (Auth.)

Practical relevance of pattern uniqueness in forensic science.

Science.gov (United States)

Jayaprakash, Paul T

2013-09-10

Uniqueness being unprovable, it has recently been argued that individualization in forensic science is irrelevant and, probability, as applied for DNA profiles, should be applied for all identifications. Critiques against uniqueness have omitted physical matching, a realistic and tangible individualization that supports uniqueness. Describing case examples illustrating pattern matches including physical matching, it is indicated that individualizations are practically relevant for forensic science as they establish facts on a definitive basis providing firm leads benefitting criminal investigation. As a tenet of forensic identification, uniqueness forms a fundamental paradigm relevant for individualization. Evidence on the indeterministic and stochastic causal pathways of characteristics in patterns available in the related fields of science sufficiently supports the proposition of uniqueness. Characteristics involved in physical matching and matching achieved in patterned evidence existing in the state of nature are not events amenable for counting; instead these are ensemble of visible units occupying the entire pattern area stretching the probability of re-occurrence of a verisimilitude pattern into infinity offering epistemic support to uniqueness. Observational methods are as respectable as instrumental or statistical methods since they are capable of generating results that are tangible and obviously valid as in physical matching. Applying the probabilistic interpretation used for DNA profiles to the other patterns would be unbefitting since these two are disparate, the causal pathways of the events, the loci, in the manipulated DNA profiles being determinable. While uniqueness enables individualizations, it does not vouch for eliminating errors. Instead of dismissing uniqueness and individualization, accepting errors as human or system failures and seeking remedial measures would benefit forensic science practice and criminal investigation. Copyright © 2013

Endocytosis of G protein-coupled receptors is regulated by clathrin light chain phosphorylation.

Science.gov (United States)

Ferreira, Filipe; Foley, Matthew; Cooke, Alex; Cunningham, Margaret; Smith, Gemma; Woolley, Robert; Henderson, Graeme; Kelly, Eamonn; Mundell, Stuart; Smythe, Elizabeth

2012-08-07

Signaling by transmembrane receptors such as G protein-coupled receptors (GPCRs) occurs at the cell surface and throughout the endocytic pathway, and signaling from the cell surface may differ in magnitude and downstream output from intracellular signaling. As a result, the rate at which signaling molecules traverse the endocytic pathway makes a significant contribution to downstream output. Modulation of the core endocytic machinery facilitates differential uptake of individual cargoes. Clathrin-coated pits are a major entry portal where assembled clathrin forms a lattice around invaginating buds that have captured endocytic cargo. Clathrin assembles into triskelia composed of three clathrin heavy chains and associated clathrin light chains (CLCs). Despite the identification of clathrin-coated pits at the cell surface over 30 years ago, the functions of CLCs in endocytosis have been elusive. In this work, we identify a novel role for CLCs in the regulated endocytosis of specific cargoes. Small interfering RNA-mediated knockdown of either CLCa or CLCb inhibits the uptake of GPCRs. Moreover, we demonstrate that phosphorylation of Ser204 in CLCb is required for efficient endocytosis of a subset of GPCRs and identify G protein-coupled receptor kinase 2 (GRK2) as a kinase that can phosphorylate CLCb on Ser204. Overexpression of CLCb(S204A) specifically inhibits the endocytosis of those GPCRs whose endocytosis is GRK2-dependent. Together, these results indicate that CLCb phosphorylation acts as a discriminator for the endocytosis of specific GPCRs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Uniqueness theorem for static phantom wormholes in Einstein–Maxwell-dilaton theory

Directory of Open Access Journals (Sweden)

Boian Lazov

2018-03-01

Full Text Available We prove a uniqueness theorem for completely regular traversable electrically charged wormhole solutions in the Einstein–Maxwell-dilaton gravity with a phantom scalar field and a possible phantom electromagnetic field. In a certain region of the parameter space, determined by the asymptotic values of the scalar field and the lapse function, the regular wormholes are completely specified by their mass, scalar charge and electric charge. The argument is based on the positive energy theorem applied on an appropriate conformally transformed Riemannian space.

Unique roles of antisocial personality disorder and psychopathic traits in distress tolerance.

Science.gov (United States)

Sargeant, Marsha N; Daughters, Stacey B; Curtin, John J; Schuster, Randi; Lejuez, C W

2011-11-01

Previous research indicates that individuals with antisocial personality disorder (ASPD) evidence low distress tolerance, which signifies impaired ability to persist in goal-directed behavior during an aversive situation, and is associated with a variety of poor interpersonal and drug use outcomes. Based on theory and research indicating that psychopathic traits are associated with hypo-reactivity in emotional responding, a unique hypothesis emerges where psychopathic traits should have the opposite effect of ASPD and be related to high levels of distress tolerance. In a sample of 107 substance-dependent patients in an inner-city substance use residential treatment facility, this hypothesis was supported. ASPD was related to lower distress tolerance, while psychopathic traits were related to higher distress tolerance, with each contributing unique variance. Findings are discussed in relation to different presentations of distress tolerance as a function of psychopathic traits among those with an ASPD diagnosis.

Human uniqueness-self-interest and social cooperation.

Science.gov (United States)

Okada, Daijiro; Bingham, Paul M

2008-07-21

Humans are unique among all species of terrestrial history in both ecological dominance and individual properties. Many, or perhaps all, of the unique elements of this nonpareil status can be plausibly interpreted as evolutionary and strategic elements and consequences of the unprecedented intensity and scale of our social cooperation. Convincing explanation of this unique human social adaptation remains a central, unmet challenge to the scientific enterprise. We develop a hypothesis for the ancestral origin of expanded cooperative social behavior. Specifically, we present a game theoretic analysis demonstrating that a specific pattern of expanded social cooperation between conspecific individuals with conflicts of interest (including non-kin) can be strategically viable, but only in animals that possess a highly unusual capacity for conspecific violence (credible threat) having very specific properties that dramatically reduce the costs of coercive violence. The resulting reduced costs allow preemptive or compensated coercion to be an instantaneously self-interested behavior under diverse circumstances rather than in rare, idiosyncratic circumstances as in actors (animals) who do not have access to inexpensive coercive threat. Humans are apparently unique among terrestrial organisms in having evolved conspecific coercive capabilities that fulfill these stringent requirements. Thus, our results support the proposal that access to a novel capacity for projection of coercive threat might represent the essential initiating event for the evolution of a human-like pattern of social cooperation and the subsequent evolution of the diverse features of human uniqueness. Empirical evidence indicates that these constraints were, in fact, met only in our evolutionary lineage. The logic for the emergence of uniquely human cooperation suggested by our analysis apparently accounts simply for the human fossil record.

The Glory Program: Global Science from a Unique Spacecraft Integration

Science.gov (United States)

Bajpayee Jaya; Durham, Darcie; Ichkawich, Thomas

2006-01-01

The Glory program is an Earth and Solar science mission designed to broaden science community knowledge of the environment. The causes and effects of global warming have become a concern in recent years and Glory aims to contribute to the knowledge base of the science community. Glory is designed for two functions: one is solar viewing to monitor the total solar irradiance and the other is observing the Earth s atmosphere for aerosol composition. The former is done with an active cavity radiometer, while the latter is accomplished with an aerosol polarimeter sensor to discern atmospheric particles. The Glory program is managed by NASA Goddard Space Flight Center (GSFC) with Orbital Sciences in Dulles, VA as the prime contractor for the spacecraft bus, mission operations, and ground system. This paper will describe some of the more unique features of the Glory program including the integration and testing of the satellite and instruments as well as the science data processing. The spacecraft integration and test approach requires extensive analysis and additional planning to ensure existing components are successfully functioning with the new Glory components. The science mission data analysis requires development of mission unique processing systems and algorithms. Science data analysis and distribution will utilize our national assets at the Goddard Institute for Space Studies (GISS) and the University of Colorado's Laboratory for Atmospheric and Space Physics (LASP). The Satellite was originally designed and built for the Vegetation Canopy Lidar (VCL) mission, which was terminated in the middle of integration and testing due to payload development issues. The bus was then placed in secure storage in 2001 and removed from an environmentally controlled container in late 2003 to be refurbished to meet the Glory program requirements. Functional testing of all the components was done as a system at the start of the program, very different from a traditional program

Constructing Dense Graphs with Unique Hamiltonian Cycles

Science.gov (United States)

Lynch, Mark A. M.

2012-01-01

It is not difficult to construct dense graphs containing Hamiltonian cycles, but it is difficult to generate dense graphs that are guaranteed to contain a unique Hamiltonian cycle. This article presents an algorithm for generating arbitrarily large simple graphs containing "unique" Hamiltonian cycles. These graphs can be turned into dense graphs…

A Unique Fungal Two-Component System Regulates Stress Responses, Drug Sensitivity, Sexual Development, and Virulence of Cryptococcus neoformans

Science.gov (United States)

Bahn, Yong-Sun; Kojima, Kaihei; Cox, Gary M.

2006-01-01

The stress-activated mitogen-activated protein kinase (MAPK) pathway is widely used by eukaryotic organisms as a central conduit via which cellular responses to the environment effect growth and differentiation. The basidiomycetous human fungal pathogen Cryptococcus neoformans uniquely uses the stress-activated Pbs2-Hog1 MAPK system to govern a plethora of cellular events, including stress responses, drug sensitivity, sexual reproduction, and virulence. Here, we characterized a fungal “two-component” system that controls these fundamental cellular functions via the Pbs2-Hog1 MAPK cascade. A typical response regulator, Ssk1, modulated all Hog1-dependent phenotypes by controlling Hog1 phosphorylation, indicating that Ssk1 is the major upstream signaling component of the Pbs2-Hog1 pathway. A second response regulator, Skn7, governs sensitivity to Na+ ions and the antifungal agent fludioxonil, negatively controls melanin production, and functions independently of Hog1 regulation. To control these response regulators, C. neoformans uses multiple sensor kinases, including two-component–like (Tco) 1 and Tco2. Tco1 and Tco2 play shared and distinct roles in stress responses and drug sensitivity through the Hog1 MAPK system. Furthermore, each sensor kinase mediates unique cellular functions for virulence and morphological differentiation. Our findings highlight unique adaptations of this global two-component MAPK signaling cascade in a ubiquitous human fungal pathogen. PMID:16672377

Novel criteria of uniqueness for signal reconstruction from phase

NARCIS (Netherlands)

Ma, C.

1991-01-01

An approach for ascertaining whether a signal is uniquely determined by its Fourier transform phase is proposed. It is shown that uniqueness corresponds to the nonsingularity of a matrix which can be formed from the finite-length real sequence. The criterion of uniqueness for reconstructing a

Fiscal 1998 research report on application technology of molecular assemblies for a functional protein system (Development of advanced maintenance technology for power plants); 1998 nendo kinosei tanpakushitsu shugotai oyo gijutsu no kenkyu kaihatsu. Hatsuden shisetsuyo kokino mentenansu gijutsu kaihatsu seika hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-03-01

Basic research was made on engineering reappearance and industrial use of the complex function of molecular assemblies for a functional protein system of organisms. In research on a light controllable reaction system by physicochemical technique, construction of a light controllable bioreactor is in promotion. In research on a light controllable reaction system by biochemical technique, researches are in promotion on structure and correlation analysis of photosynthetic protein complex, stabilization of an activity, and conversion of light energy to membrane transport energy using cyanobacteria as material. In research on a molecular recognition controllable reaction system in a fine membrane region, correlation analysis of the structure and function of glutamine receptor channels is in promotion. In addition, researches were made on reconstitution of endocytic micromachinery, a multi-enzyme system for synthesis of glycosphingolipids, a complex redox system by genetic engineering technique, and application technology of molecular assemblies for a functional protein system. (NEDO)

Endocytic mechanisms and osteoinductive profile of hydroxyapatite nanoparticles in human umbilical cord Wharton’s jelly-derived mesenchymal stem cells

Science.gov (United States)

Zhang, Juan; Wang, Chen

2018-01-01

Background As a potentially bioactive material, the widespread application of nanosized hydroxyapatite (nano-HAP) in the field of bone regeneration has increased the risk of human exposure. However, our understanding of the interaction between nano-HAP and stem cells implicated in bone repair remains incomplete. Methods Here, we characterized the adhesion and cellular internalization of HAP nanoparticles (HANPs) with different sizes (20 nm np20 and 80 nm np80) and highlighted the involved pathway in their uptake using human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (hWJ-MSCs). In addition, the effects of HANPs on cell viability, apoptosis response, osteogenic differentiation, and underlying related mechanisms were explored. Results It was shown that both types of HANPs readily adhered to the cellular membrane and were transported into the cells compared to micro-sized HAP particles (m-HAP; 12 μm). Interestingly, the endocytic routes of np20 and np80 differed, although they exhibited similar kinetics of adhesion and uptake. Our study revealed involvement of clathrin- and caveolin-mediated endocytosis as well as macropinocytosis in the np20 uptake. However, for np80, clathrin-mediated endocytosis and some as-yet-unidentified important uptake routes play central roles in their internalization. HANPs displayed a higher preference to accumulate in the cytoplasm compared to m-HAP, and HANPs were not detected in the nucleolus. Exposure to np20 for 24 h caused a decrease in cell viability, while cells completely recovered with an exposure time of 72 h. Furthermore, HANPs did not influence apoptosis and necrosis of hWJ-MSCs. Strikingly, HANPs enhanced mRNA levels of osteoblast-related genes and stimulated calcium mineral deposition, and this directly correlated with the activation in c-Jun N-terminal kinases and p38 pathways. Conclusion Our data provide additional insight about the interactions of HANPs with MSCs and suggest their application

STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma membrane, ER, and ERC.

Science.gov (United States)

Garbarino, Jeanne; Pan, Meihui; Chin, Harvey F; Lund, Frederik W; Maxfield, Frederick R; Breslow, Jan L

2012-12-01

STARD4, a member of the evolutionarily conserved START gene family, has been implicated in the nonvesicular intracellular transport of cholesterol. However, the direction of transport and the membranes with which this protein interacts are not clear. We present studies of STARD4 function using small hairpin RNA knockdown technology to reduce STARD4 expression in HepG2 cells. In a cholesterol-poor environment, we found that a reduction in STARD4 expression leads to retention of cholesterol at the plasma membrane, reduction of endoplasmic reticulum-associated cholesterol, and decreased ACAT synthesized cholesteryl esters. Furthermore, D4 KD cells exhibited a reduced rate of sterol transport to the endocytic recycling compartment after cholesterol repletion. Although these cells displayed normal endocytic trafficking in cholesterol-poor and replete conditions, cell surface low density lipoprotein receptor (LDLR) levels were increased and decreased, respectively. We also observed a decrease in NPC1 protein expression, suggesting the induction of compensatory pathways to maintain cholesterol balance. These data indicate a role for STARD4 in nonvesicular transport of cholesterol from the plasma membrane and the endocytic recycling compartment to the endoplasmic reticulum and perhaps other intracellular compartments as well.

Salivary gland NK cells are phenotypically and functionally unique.

Directory of Open Access Journals (Sweden)

Marlowe S Tessmer

2011-01-01

Full Text Available Natural killer (NK cells and CD8(+ T cells play vital roles in containing and eliminating systemic cytomegalovirus (CMV. However, CMV has a tropism for the salivary gland acinar epithelial cells and persists in this organ for several weeks after primary infection. Here we characterize a distinct NK cell population that resides in the salivary gland, uncommon to any described to date, expressing both mature and immature NK cell markers. Using RORγt reporter mice and nude mice, we also show that the salivary gland NK cells are not lymphoid tissue inducer NK-like cells and are not thymic derived. During the course of murine cytomegalovirus (MCMV infection, we found that salivary gland NK cells detect the infection and acquire activation markers, but have limited capacity to produce IFN-γ and degranulate. Salivary gland NK cell effector functions are not regulated by iNKT or T(reg cells, which are mostly absent in the salivary gland. Additionally, we demonstrate that peripheral NK cells are not recruited to this organ even after the systemic infection has been controlled. Altogether, these results indicate that viral persistence and latency in the salivary glands may be due in part to the presence of unfit NK cells and the lack of recruitment of peripheral NK cells.

Diabetes: Unique to Older Adults

Science.gov (United States)

... Stroke Urinary Incontinence Related Documents PDF Choosing Wisely: Diabetes Tests and Treatments Download Related Video Join our e-newsletter! Aging & Health A to Z Diabetes Unique to Older Adults This section provides information ...

Unique cerebrovascular anomalies in Noonan syndrome with RAF1 mutation.

Science.gov (United States)

Zarate, Yuri A; Lichty, Angie W; Champion, Kristen J; Clarkson, L Kate; Holden, Kenton R; Matheus, M Gisele

2014-08-01

Noonan syndrome is a common autosomal dominant neurodevelopmental disorder caused by gain-of-function germline mutations affecting components of the Ras-MAPK pathway. The authors present the case of a 6-year-old male with Noonan syndrome, Chiari malformation type I, shunted benign external hydrocephalus in infancy, and unique cerebrovascular changes. A de novo heterozygous change in the RAF1 gene was identified. The patient underwent brain magnetic resonance imaging, computed tomography angiography, and magnetic resonance angiography to further clarify the nature of his abnormal brain vasculature. The authors compared his findings to the few cases of Noonan syndrome reported with cerebrovascular pathology. © The Author(s) 2013.

The potential of tumor-derived exosomes for noninvasive cancer monitoring.

Science.gov (United States)

Whiteside, Theresa L

2015-01-01

Tumor-derived exosomes (TEX) are emerging as a new type of cancer biomarker. TEX are membrane-bound, virus-size vesicles of endocytic origin present in all body fluids of cancer patients. Based on the expanding albeit incomplete knowledge of their biogenesis, secretion by tumor cells and cancer cell-specific molecular and genetic contents, TEX are viewed as promising, clinically-relevant surrogates of cancer progression and response to therapy. Preliminary proteomic, genetic and functional profiling of tumor cell-derived or cancer plasma-derived exosomes confirms their unique characteristics. Alterations in protein or nucleic acid profiles of exosomes in plasma of cancer patients responding to therapies appear to correlate with clinical endpoints. However, methods for TEX isolation and separation from the bulk of human plasma-derived exosomes are not yet established and their role as biomarkers remains to be confirmed. Further development and validation of TEX as noninvasive, liquid equivalents of tumor biopsies are necessary to move this effort forward.

Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells

Science.gov (United States)

Kraehling, Jan R.; Chidlow, John H.; Rajagopal, Chitra; Sugiyama, Michael G.; Fowler, Joseph W.; Lee, Monica Y.; Zhang, Xinbo; Ramírez, Cristina M.; Park, Eon Joo; Tao, Bo; Chen, Keyang; Kuruvilla, Leena; Larriveé, Bruno; Folta-Stogniew, Ewa; Ola, Roxana; Rotllan, Noemi; Zhou, Wenping; Nagle, Michael W.; Herz, Joachim; Williams, Kevin Jon; Eichmann, Anne; Lee, Warren L.; Fernández-Hernando, Carlos; Sessa, William C.

2016-01-01

In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma still readily traverses the endothelium. To identify the pathways of LDL uptake, a genome-wide RNAi screen was performed in endothelial cells and cross-referenced with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake of LDL into endothelial cells via an unusual endocytic pathway that diverts the ligand from lysosomal degradation and promotes LDL transcytosis. The endothelium-specific genetic ablation of Alk1 in Ldlr-KO animals leads to less LDL uptake into the aortic endothelium, showing its physiological role in endothelial lipoprotein metabolism. In summary, identification of pathways mediating LDLR-independent uptake of LDL may provide unique opportunities to block the initiation of LDL accumulation in the vessel wall or augment hepatic LDLR-dependent clearance of LDL. PMID:27869117

Creativity and technical innovation: spatial ability's unique role.

Science.gov (United States)

Kell, Harrison J; Lubinski, David; Benbow, Camilla P; Steiger, James H

2013-09-01

In the late 1970s, 563 intellectually talented 13-year-olds (identified by the SAT as in the top 0.5% of ability) were assessed on spatial ability. More than 30 years later, the present study evaluated whether spatial ability provided incremental validity (beyond the SAT's mathematical and verbal reasoning subtests) for differentially predicting which of these individuals had patents and three classes of refereed publications. A two-step discriminant-function analysis revealed that the SAT subtests jointly accounted for 10.8% of the variance among these outcomes (p development of creativity, beyond the roles played by the abilities traditionally measured in educational selection, counseling, and industrial-organizational psychology. Spatial ability plays a key and unique role in structuring many important psychological phenomena and should be examined more broadly across the applied and basic psychological sciences.

Might "Unique" Factors Be "Common"? On the Possibility of Indeterminate Common-Unique Covariances

Science.gov (United States)

Grayson, Dave

2006-01-01

The present paper shows that the usual factor analytic structured data dispersion matrix lambda psi lambda' + delta can readily arise from a set of scores y = lambda eta + epsilon, shere the "common" (eta) and "unique" (epsilon) factors have nonzero covariance: gamma = Cov epsilon,eta) is not equal to 0. Implications of this finding are discussed…

Border patrol: insights into the unique role of perlecan/heparan sulfate proteoglycan 2 at cell and tissue borders.

Science.gov (United States)

Farach-Carson, Mary C; Warren, Curtis R; Harrington, Daniel A; Carson, Daniel D

2014-02-01

The extracellular matrix proteoglycan (ECM) perlecan, also known as heparan sulfate proteoglycan 2 or HSPG2, is one of the largest (>200 nm) and oldest (>550 M years) extracellular matrix molecules. In vertebrates, perlecan's five-domain structure contains numerous independently folding modules with sequence similarities to other ECM proteins, all connected like cars into one long, diverse complex train following a unique N-terminal domain I decorated with three long glycosaminoglycan chains, and an additional glycosaminoglycan attachment site in the C-terminal domain V. In lower invertebrates, perlecan is not typically a proteoglycan, possessing the majority of the core protein modules, but lacking domain I where the attachment sites for glycosaminoglycan chains are located. This suggests that uniting the heparan sulfate binding growth factor functions of domain I and the core protein functions of the rest of the molecule in domains II-V occurred later in evolution for a new functional purpose. In this review, we surveyed several decades of pertinent literature to ask a fundamental question: Why did nature design this protein uniquely as an extraordinarily long multifunctional proteoglycan with a single promoter regulating expression, rather than separating these functions into individual proteins that could be independently regulated? We arrived at the conclusion that the concentration of perlecan at functional borders separating tissues and tissue layers is an ancient key function of the core protein. The addition of the heparan sulfate chains in domain I likely occurred as an additional means of binding the core protein to other ECM proteins in territorial matrices and basement membranes, and as a means to reserve growth factors in an on-site depot to assist with rapid repair of those borders when compromised, such as would occur during wounding. We propose a function for perlecan that extends its role from that of an extracellular scaffold, as we previously

Customization: Ideal Varieties, Product Uniqueness and Price Competition

OpenAIRE

Oksana Loginova; X. Henry Wang

2009-01-01

We study customization in the Hotelling model with two firms. In addition to providing ideal varieties, the perceived uniqueness of a customized product contributes independently to consumer utility. We show that only when consumer preferences for uniqueness are high customization occurs in equilibrium.

Hausdorff dimension of unique beta expansions

International Nuclear Information System (INIS)

Kong, Derong; Li, Wenxia

2015-01-01

Given an integer N ⩾ 2 and a real number β > 1, let Γ β, N be the set of all x=∑ i=1 ∞ d i /β i with d i  ∈ {0, 1, ···, N − 1} for all i ⩾ 1. The infinite sequence (d i ) is called a β-expansion of x. Let U β,N be the set of all x's in Γ β,N which have unique β-expansions. We give explicit formula of the Hausdorff dimension of U β,N for β in any admissible interval [β L , β U ], where β L is a purely Parry number while β U is a transcendental number whose quasi-greedy expansion of 1 is related to the classical Thue–Morse sequence. This allows us to calculate the Hausdorff dimension of U β,N for almost every β > 1. In particular, this improves the main results of Gábor Kallós (1999, 2001). Moreover, we find that the dimension function f(β) = dim H U β,N fluctuates frequently for β ∈ (1, N). (paper)

Can facial uniqueness be inferred from impostor scores?

NARCIS (Netherlands)

Dutta, A.; Veldhuis, Raymond N.J.; Spreeuwers, Lieuwe Jan

2013-01-01

In Biometrics, facial uniqueness is commonly inferred from impostor similarity scores. In this paper, we show that such uniqueness measures are highly unstable in the presence of image quality variations like pose, noise and blur. We also experimentally demonstrate the instability of a recently

Unique relations between post-traumatic stress disorder symptoms and patient functioning in type 2 diabetes.

Science.gov (United States)

Arigo, Danielle; Juth, Vanessa; Trief, Paula; Wallston, Kenneth; Ulbrecht, Jan; Smyth, Joshua M

2017-08-01

This study examined reported post-traumatic stress disorder symptoms in adults with poorly controlled type 2 diabetes who had no history of psychiatric diagnosis or treatment ( n = 184, M HbA1c  = 9.13%, standard deviation = 1.68). Participants reported moderate to severe intensity of post-traumatic stress disorder symptoms ( M = 19.17, SD = 17.58). Together, depressive and post-traumatic stress disorder symptoms accounted for 10-40 percent of the variance in type 2 diabetes outcomes; post-traumatic stress disorder symptoms were associated with elevated diabetes distress and more frequent exercise and self-blood glucose testing (unique R 2  ~ 3%). Post-traumatic stress disorder symptoms may be overlooked in type 2 diabetes among patients without formal psychiatric diagnoses, and warrant increased attention.

Kosovo case: A unique arbitrariness

Directory of Open Access Journals (Sweden)

Nakarada Radmila

2007-01-01

Full Text Available The end of Cold war, contrary to expectations has brought new conflicts and forms of violence, new divisions and new relativizations of the international legal order. Taking as an example the endeavors to resolve the Kosovo conflict, the author attempts to indicate the broader implications of the international efforts to constitute an independent state on part of the territory of an existing sovereign state. The arguments used to justify the redefinition of the borders of the Serbian state without its consent, the moral, democratic, peace arguments, are reviewed. Particular attention is paid to the argument that Kosovo is a unique case and therefore unique rules should be applied. The author seeks to understand the deeper significance of these efforts, concluding that dismantling the present international legal order is not only a potential danger but a possible aim.

Bioinformatic and Comparative Localization of Rab Proteins Reveals Functional Insights into the Uncharacterized GTPases Ypt10p and Ypt11p†

Science.gov (United States)

Buvelot Frei, Stéphanie; Rahl, Peter B.; Nussbaum, Maria; Briggs, Benjamin J.; Calero, Monica; Janeczko, Stephanie; Regan, Andrew D.; Chen, Catherine Z.; Barral, Yves; Whittaker, Gary R.; Collins, Ruth N.

2006-01-01

A striking characteristic of a Rab protein is its steady-state localization to the cytosolic surface of a particular subcellular membrane. In this study, we have undertaken a combined bioinformatic and experimental approach to examine the evolutionary conservation of Rab protein localization. A comprehensive primary sequence classification shows that 10 out of the 11 Rab proteins identified in the yeast (Saccharomyces cerevisiae) genome can be grouped within a major subclass, each comprising multiple Rab orthologs from diverse species. We compared the locations of individual yeast Rab proteins with their localizations following ectopic expression in mammalian cells. Our results suggest that green fluorescent protein-tagged Rab proteins maintain localizations across large evolutionary distances and that the major known player in the Rab localization pathway, mammalian Rab-GDI, is able to function in yeast. These findings enable us to provide insight into novel gene functions and classify the uncharacterized Rab proteins Ypt10p (YBR264C) as being involved in endocytic function and Ypt11p (YNL304W) as being localized to the endoplasmic reticulum, where we demonstrate it is required for organelle inheritance. PMID:16980630

Uniqueness of thermodynamic projector and kinetic basis of molecular individualism

Science.gov (United States)

Gorban, Alexander N.; Karlin, Iliya V.

2004-05-01

Three results are presented: First, we solve the problem of persistence of dissipation for reduction of kinetic models. Kinetic equations with thermodynamic Lyapunov functions are studied. Uniqueness of the thermodynamic projector is proven: There exists only one projector which transforms any vector field equipped with the given Lyapunov function into a vector field with the same Lyapunov function for a given anzatz manifold which is not tangent to the Lyapunov function levels. Second, we use the thermodynamic projector for developing the short memory approximation and coarse-graining for general nonlinear dynamic systems. We prove that in this approximation the entropy production increases. ( The theorem about entropy overproduction.) In example, we apply the thermodynamic projector to derive the equations of reduced kinetics for the Fokker-Planck equation. A new class of closures is developed, the kinetic multipeak polyhedra. Distributions of this type are expected in kinetic models with multidimensional instability as universally as the Gaussian distribution appears for stable systems. The number of possible relatively stable states of a nonequilibrium system grows as 2 m, and the number of macroscopic parameters is in order mn, where n is the dimension of configuration space, and m is the number of independent unstable directions in this space. The elaborated class of closures and equations pretends to describe the effects of “molecular individualism”. This is the third result.

Unique and shared roles of the posterior parietal and dorsolateral prefrontal cortex in cognitive functions

Directory of Open Access Journals (Sweden)

Fumi eKatsuki

2012-05-01

Full Text Available The dorsolateral prefrontal and posterior parietal cortex are two parts of a broader brain network involved in the control of cognitive functions such as working memory, spatial attention, and decision making. The two areas share many functional properties and exhibit similar patterns of activation during the execution of mental operations. However, neurophysiological experiments in non-human primates have also documented subtle differences, revealing functional specialization within the fronto-parietal network. These differences include the ability of the dorsolateral prefrontal cortex to influence memory performance, attention allocation and motor responses to a greater extent, and to resist interference by distracting stimuli. In recent years, distinct cellular and anatomical differences have been identified, offering insights into how functional specialization is achieved. This article reviews the common functions and functional differences between the dorsolateral prefrontal and posterior parietal cortex, and their underlying mechanisms.

Capillary pressure as a unique function of electric permittivity and water saturation

NARCIS (Netherlands)

Plug, W.J.; Slob, E.; Van Turnhout, J.; Bruining, J.

2007-01-01

The relation between capillary pressure (Pc) and interfacial area has been investigated by measuring Pc and the electric permittivity at 100 kHz simultaneously as function of the water saturation, (Sw). Drainage and imbibition experiments have been conducted for sand-distilled water-gas (CO2/N2)

Cyclic adenosine monophosphate levels and the function of skin microvascular endothelial cells.

Science.gov (United States)

Tuder, R M; Karasek, M A; Bensch, K G

1990-02-01

The maintenance of the normal epithelioid morphology of human dermal microvascular endothelial cells (MEC) grown in vitro depends strongly on the presence of factors that increase intracellular levels of cyclic AMP. Complete removal of dibutyryl cAMP and isobutylmethylxanthine (IMX) from the growth medium results in a progressive transition from an epithelioid to a spindle-shaped cell line. This transition cannot be reversed by the readdition of dibutyryl cAMP and IMX to the growth medium or by addition of agonists that increase cAMP levels. Spindle-shaped MEC lose the ability to express Factor VIII rAG and DR antigens and to bind peripheral blood mononuclear leukocyte (PBML). Ultrastructural analyses of transitional cells and spindle-shaped cells show decreased numbers of Weibel-Palade bodies in transitional cells and their complete absence in spindle-shaped cells. Interferon-gamma alters several functional properties of both epithelioid and spindle-shaped cells. In the absence of dibutyryl cAMP it accelerates the transition from epithelial to spindle-shaped cells, whereas in the presence of cyclic AMP interferon-gamma increases the binding of PBMLs to both epithelioid and spindle-shaped MEC and the endocytic activity of the endothelial cells. These results suggest that cyclic AMP is an important second messenger in the maintenance of several key functions of microvascular endothelial cells. Factors that influence the levels of this messenger in vivo can be expected to influence the angiogenic and immunologic functions of the microvasculature.

Interaction between the cardiac rapidly (IKr) and slowly (IKs) activating delayed rectifier potassium channels revealed by low K+-induced hERG endocytic degradation.

Science.gov (United States)

Guo, Jun; Wang, Tingzhong; Yang, Tonghua; Xu, Jianmin; Li, Wentao; Fridman, Michael D; Fisher, John T; Zhang, Shetuan

2011-10-07

Cardiac repolarization is controlled by the rapidly (I(Kr)) and slowly (I(Ks)) activating delayed rectifier potassium channels. The human ether-a-go-go-related gene (hERG) encodes I(Kr), whereas KCNQ1 and KCNE1 together encode I(Ks). Decreases in I(Kr) or I(Ks) cause long QT syndrome (LQTS), a cardiac disorder with a high risk of sudden death. A reduction in extracellular K(+) concentration ([K(+)](o)) induces LQTS and selectively causes endocytic degradation of mature hERG channels from the plasma membrane. In the present study, we investigated whether I(Ks) compensates for the reduced I(Kr) under low K(+) conditions. Our data show that when hERG and KCNQ1 were expressed separately in human embryonic kidney (HEK) cells, exposure to 0 mM K(+) for 6 h completely eliminated the mature hERG channel expression but had no effect on KCNQ1. When hERG and KCNQ1 were co-expressed, KCNQ1 significantly delayed 0 mM K(+)-induced hERG reduction. Also, hERG degradation led to a significant reduction in KCNQ1 in 0 mM K(+) conditions. An interaction between hERG and KCNQ1 was identified in hERG+KCNQ1-expressing HEK cells. Furthermore, KCNQ1 preferentially co-immunoprecipitated with mature hERG channels that are localized in the plasma membrane. Biophysical and pharmacological analyses indicate that although hERG and KCNQ1 closely interact with each other, they form distinct hERG and KCNQ1 channels. These data extend our understanding of delayed rectifier potassium channel trafficking and regulation, as well as the pathology of LQTS.

Uniqueness of Positive Solutions of Δu+f(u)=0 in N, N<=3

Science.gov (United States)

Cortázar, Carmen; Elgueta, Manuel; Felmer, Patricio

We study the uniqueness of radial ground states for the semilinear elliptic partial differential equation $Δ u+f(u)=0 {(*)}$ in N. We assume that the function f has two zeros, the origin and u0>0. Above u0 the function f is positive, is locally Lipschitz continuous and satisfies convexity and growth conditions of a superlinear nature. Below u0, f is assumed to be non-positive, non-identically zero and merely continuous. Our results are obtained through a careful analysis of the solutions of an associated initial-value problem, and the use of a monotone separation theorem. It is known that, for a large class of functions f, the ground states of (*) are radially symmetric. In these cases our result implies that (*) possesses at most one ground state.

Unique interaction pattern for a functionally biased ghrelin receptor agonist

DEFF Research Database (Denmark)

Sivertsen, Bjørn Behrens; Lang, Manja; Frimurer, Thomas M.

2011-01-01

Based on the conformationally constrained D-Trp-Phe-D-Trp (wFw) core of the prototype inverse agonist [D-Arg(1),D-Phe(5),D-Trp(7,9),Leu(11)]substance P, a series of novel, small, peptide-mimetic agonists for the ghrelin receptor were generated. By using various simple, ring-constrained spacers...... connecting the D-Trp-Phe-D-Trp motif with the important C-terminal carboxyamide group, 40 nm agonism potency was obtained and also in one case (wFw-Isn-NH(2), where Isn is isonipecotic acid) ~80% efficacy. However, in contrast to all previously reported ghrelin receptor agonists, the piperidine-constrained w......Fw-Isn-NH(2) was found to be a functionally biased agonist. Thus, wFw-Isn-NH(2) mediated potent and efficacious signaling through the Ga(q) and ERK1/2 signaling pathways, but in contrast to all previous ghrelin receptor agonists it did not signal through the serum response element, conceivably the Ga(12...

Uniqueness of family therapists as family business systems consultants: a cross-disciplinary investigation.

Science.gov (United States)

Lee, Jinhee; Danes, Sharon M

2012-06-01

The purpose of this study is to address how the consulting approaches of family therapists working with family businesses differ from those of business consultants. The logic of analytic induction was used to analyze qualitative data from family business consultants with and without training in family therapy. Consultants were asked to respond to two vignettes: one emphasized primarily family system problems, whereas the other emphasized business problems with influencing issues at the family/business intersection. Both similarities and differences were found in reference to problem assessment, consulting goal orientation, intervention strategy focus, consultant role and function, and consulting setting preference between consultants with and without family therapy training. Results indicate that consultants of each discipline provide a unique perspective and expertise that allow them to successfully address the spectrum of issues that family firms face. Further, findings highlight the unique contribution of family therapists to an interdisciplinary consulting team. © 2012 American Association for Marriage and Family Therapy.

Mechanistic Insights into the Unique Role of Copper in CO2 Electroreduction Reactions.

Science.gov (United States)

Liu, Shan Ping; Zhao, Ming; Gao, Wang; Jiang, Qing

2017-01-20

Cu demonstrates a unique capability towards CO 2 electroreduction that can close the anthropogenic carbon cycle; however, its reaction mechanism remains elusive, owing to the obscurity of the solid-liquid interface on Cu surfaces where electrochemical reactions occur. Using a genetic algorithm method in addition to density functional theory, we explicitly identify the configuration of a water bilayer on Cu(2 1 1) and build electrochemical models. These enable us to reveal a mechanistic picture for CO 2 electroreduction, finding the key intermediates CCO* for the C 2 H 4 pathway and CH* for the CH 4 pathway, which rationalize a series of experimental observations. Furthermore, we find that the interplay between the Cu surfaces, carbon monomers, and water network (but not the binding of CO*) essentially determine the unique capability of Cu towards CO 2 electroreduction, proposing a new and effective descriptor for exploiting optimal catalysts. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Addressing Uniqueness and Unison of Reliability and Safety for a Better Integration

Science.gov (United States)

Huang, Zhaofeng; Safie, Fayssal

2016-01-01

Over time, it has been observed that Safety and Reliability have not been clearly differentiated, which leads to confusion, inefficiency, and, sometimes, counter-productive practices in executing each of these two disciplines. It is imperative to address this situation to help Reliability and Safety disciplines improve their effectiveness and efficiency. The paper poses an important question to address, "Safety and Reliability - Are they unique or unisonous?" To answer the question, the paper reviewed several most commonly used analyses from each of the disciplines, namely, FMEA, reliability allocation and prediction, reliability design involvement, system safety hazard analysis, Fault Tree Analysis, and Probabilistic Risk Assessment. The paper pointed out uniqueness and unison of Safety and Reliability in their respective roles, requirements, approaches, and tools, and presented some suggestions for enhancing and improving the individual disciplines, as well as promoting the integration of the two. The paper concludes that Safety and Reliability are unique, but compensating each other in many aspects, and need to be integrated. Particularly, the individual roles of Safety and Reliability need to be differentiated, that is, Safety is to ensure and assure the product meets safety requirements, goals, or desires, and Reliability is to ensure and assure maximum achievability of intended design functions. With the integration of Safety and Reliability, personnel can be shared, tools and analyses have to be integrated, and skill sets can be possessed by the same person with the purpose of providing the best value to a product development.

An overexpression screen of Toxoplasma gondii Rab-GTPases reveals distinct transport routes to the micronemes.

Directory of Open Access Journals (Sweden)

Katrin Kremer

2013-03-01

Full Text Available The basic organisation of the endomembrane system is conserved in all eukaryotes and comparative genome analyses provides compelling evidence that the endomembrane system of the last common eukaryotic ancestor (LCEA is complex with many genes required for regulated traffic being present. Although apicomplexan parasites, causative agents of severe human and animal diseases, appear to have only a basic set of trafficking factors such as Rab-GTPases, they evolved unique secretory organelles (micronemes, rhoptries and dense granules that are sequentially secreted during invasion of the host cell. In order to define the secretory pathway of apicomplexans, we performed an overexpression screen of Rabs in Toxoplasma gondii and identified Rab5A and Rab5C as important regulators of traffic to micronemes and rhoptries. Intriguingly, we found that not all microneme proteins traffic depends on functional Rab5A and Rab5C, indicating the existence of redundant microneme targeting pathways. Using two-colour super-resolution stimulated emission depletion (STED we verified distinct localisations of independent microneme proteins and demonstrate that micronemal organelles are organised in distinct subsets or subcompartments. Our results suggest that apicomplexan parasites modify classical regulators of the endocytic system to carryout essential parasite-specific roles in the biogenesis of their unique secretory organelles.

The unique cysteine knot regulates the pleotropic hormone leptin.

Directory of Open Access Journals (Sweden)

Ellinor Haglund

Full Text Available Leptin plays a key role in regulating energy intake/expenditure, metabolism and hypertension. It folds into a four-helix bundle that binds to the extracellular receptor to initiate signaling. Our work on leptin revealed a hidden complexity in the formation of a previously un-described, cysteine-knotted topology in leptin. We hypothesized that this unique topology could offer new mechanisms in regulating the protein activity. A combination of in silico simulation and in vitro experiments was used to probe the role of the knotted topology introduced by the disulphide-bridge on leptin folding and function. Our results surprisingly show that the free energy landscape is conserved between knotted and unknotted protein, however the additional complexity added by the knot formation is structurally important. Native state analyses led to the discovery that the disulphide-bond plays an important role in receptor binding and thus mediate biological activity by local motions on distal receptor-binding sites, far removed from the disulphide-bridge. Thus, the disulphide-bridge appears to function as a point of tension that allows dissipation of stress at a distance in leptin.

Lack of RNase L attenuates macrophage functions.

Directory of Open Access Journals (Sweden)

Xin Yi

Full Text Available Macrophages are one of the major cell types in innate immunity against microbial infection. It is believed that the expression of proinflammatory genes such as tumor necrosis factor-α (TNF-α, interleukin (IL-1β, IL-6, and cyclooxygenase-2 (Cox-2 by macrophages is also crucial for activation of both innate and adaptive immunities. RNase L is an interferon (IFN inducible enzyme which is highly expressed in macrophages. It has been demonstrated that RNase L regulates the expression of certain inflammatory genes. However, its role in macrophage function is largely unknown.Bone marrow-derived macrophages (BMMs were generated from RNase L(+/+and (-/- mice. The migration of BMMs was analyzed by using Transwell migration assays. Endocytosis and phagocytosis of macrophages were assessed by using fluorescein isothiocyanate (FITC-Dextran 40,000 and FITC-E. coli bacteria, respectively. The expression of inflammatory genes was determined by Western Blot and ELISA. The promoter activity of Cox-2 was measured by luciferase reporter assays.Lack of RNase L significantly decreased the migration of BMMs induced by M-CSF, but at a less extent by GM-CSF and chemokine C-C motif ligand-2 (CCL2. Interestingly, RNase L deficient BMMs showed a significant reduction of endocytic activity to FITC-Dextran 40,000, but no any obvious effect on their phagocytic activity to FITC-bacteria under the same condition. RNase L impacts the expression of certain genes related to cell migration and inflammation such as transforming growth factor (TGF-β, IL-1β, IL-10, CCL2 and Cox-2. Furthermore, the functional analysis of the Cox-2 promoter revealed that RNase L regulated the expression of Cox-2 in macrophages at its transcriptional level. Taken together, our findings provide direct evidence showing that RNase L contributes to innate immunity through regulating macrophage functions.

Uniqueness and reconstruction of an unknown semilinear term in a time-fractional reaction–diffusion equation

KAUST Repository

Luchko, Yuri

2013-05-30

In this paper, we consider a reaction-diffusion problem with an unknown nonlinear source function that has to be determined from overposed data. The underlying model is in the form of a time-fractional reaction-diffusion equation and the work generalizes some known results for the inverse problems posed for PDEs of parabolic type. For the inverse problem under consideration, a uniqueness result is proved and a numerical algorithm with some theoretical qualification is presented in the one-dimensional case. The key both to the uniqueness result and to the numerical algorithm relies on the maximum principle which has recently been shown to hold for the fractional diffusion equation. In order to show the effectiveness of the proposed method, results of numerical simulations are presented. © 2013 IOP Publishing Ltd.

Programmable self-assembly of three-dimensional nanostructures from 10,000 unique components

Science.gov (United States)

Ong, Luvena L.; Hanikel, Nikita; Yaghi, Omar K.; Grun, Casey; Strauss, Maximilian T.; Bron, Patrick; Lai-Kee-Him, Josephine; Schueder, Florian; Wang, Bei; Wang, Pengfei; Kishi, Jocelyn Y.; Myhrvold, Cameron; Zhu, Allen; Jungmann, Ralf; Bellot, Gaetan; Ke, Yonggang; Yin, Peng

2017-12-01

Nucleic acids (DNA and RNA) are widely used to construct nanometre-scale structures with ever increasing complexity, with possible application in fields such as structural biology, biophysics, synthetic biology and photonics. The nanostructures are formed through one-pot self-assembly, with early kilodalton-scale examples containing typically tens of unique DNA strands. The introduction of DNA origami, which uses many staple strands to fold one long scaffold strand into a desired structure, has provided access to megadalton-scale nanostructures that contain hundreds of unique DNA strands. Even larger DNA origami structures are possible, but manufacturing and manipulating an increasingly long scaffold strand remains a challenge. An alternative and more readily scalable approach involves the assembly of DNA bricks, which each consist of four short binding domains arranged so that the bricks can interlock. This approach does not require a scaffold; instead, the short DNA brick strands self-assemble according to specific inter-brick interactions. First-generation bricks used to create three-dimensional structures are 32 nucleotides long, consisting of four eight-nucleotide binding domains. Protocols have been designed to direct the assembly of hundreds of distinct bricks into well formed structures, but attempts to create larger structures have encountered practical challenges and had limited success. Here we show that DNA bricks with longer, 13-nucleotide binding domains make it possible to self-assemble 0.1-1-gigadalton, three-dimensional nanostructures from tens of thousands of unique components, including a 0.5-gigadalton cuboid containing about 30,000 unique bricks and a 1-gigadalton rotationally symmetric tetramer. We also assembled a cuboid that contains around 10,000 bricks and about 20,000 uniquely addressable, 13-base-pair ‘voxels’ that serves as a molecular canvas for three-dimensional sculpting. Complex, user-prescribed, three-dimensional cavities can

DECISIONS ET COMPETITIVITE SUR LE MARCHE UNIQUE EUROPEEN

Directory of Open Access Journals (Sweden)

Sirghi Nicoleta

2008-05-01

Full Text Available L’un des traits importants du marché unique européen, a comme source le męme énoncé du principal objectif de l’intégration européenne ainsi que: l’harmonisation des niveaux du développement des Etats Membres et l’augmentation du niveau de vie dans l’ensemble de la communauté. Pour le marché unique européen, cet aspect se traduit par une permanente et soutenue augmentation de la demande. Cet ouvrage présente au début une analyse des éléments spécifiques du marché européen. Ensuite on identifie les opportunités et les risques au niveau macroéconomique adjointes aux perspectives du marché unique européen. Comme fondement on présente des stratégies du développement réalisables au niveau microéconomique que puissent assurer l’augmentation du niveau sur la compétitivité des sociétés sur le marché unique européen.

Sufficient conditions for uniqueness of the weak value

International Nuclear Information System (INIS)

Dressel, J; Jordan, A N

2012-01-01

We review and clarify the sufficient conditions for uniquely defining the generalized weak value as the weak limit of a conditioned average using the contextual values formalism introduced in Dressel, Agarwal and Jordan (2010 Phys. Rev. Lett. http://dx.doi.org/10.1103/PhysRevLett.104.240401). We also respond to criticism of our work by Parrott (arXiv:1105.4188v1) concerning a proposed counter-example to the uniqueness of the definition of the generalized weak value. The counter-example does not satisfy our prescription in the case of an underspecified measurement context. We show that when the contextual values formalism is properly applied to this example, a natural interpretation of the measurement emerges and the unique definition in the weak limit holds. We also prove a theorem regarding the uniqueness of the definition under our sufficient conditions for the general case. Finally, a second proposed counter-example by Parrott (arXiv:1105.4188v6) is shown not to satisfy the sufficiency conditions for the provided theorem. (paper)

Baleen whales host a unique gut microbiome with similarities to both carnivores and herbivores

OpenAIRE

Sanders, Jon G.; Beichman, Annabel C.; Roman, Joe; Scott, Jarrod J.; Emerson, David; McCarthy, James J.; Girguis, Peter R.

2015-01-01

Mammals host gut microbiomes of immense physiological consequence, but the determinants of diversity in these communities remain poorly understood. Diet appears to be the dominant factor, but host phylogeny also seems to be an important, if unpredictable, correlate. Here we show that baleen whales, which prey on animals (fish and crustaceans), harbor unique gut microbiomes with surprising parallels in functional capacity and higher level taxonomy to those of terrestrial herbivores. These simi...

The Eps15 C. elegans homologue EHS-1 is implicated in synaptic vesicle recycling

DEFF Research Database (Denmark)

Salcini, A E; Hilliard, M A; Croce, A

2001-01-01

implicated Eps15 in endocytosis, its function in the endocytic machinery remains unclear. Here we show that the Caenorhabditis elegans gene, zk1248.3 (ehs-1), is the orthologue of Eps15 in nematodes, and that its product, EHS-1, localizes to synaptic-rich regions. ehs-1-impaired worms showed temperature...

Unique Physician Identification Number (UPIN) Directory

Data.gov (United States)

U.S. Department of Health & Human Services — The Unique Physician Identification Number (UPIN) Directory contains selected information on physicians, doctors of Osteopathy, limited licensed practitioners and...

Regulation of VEGF signaling by membrane traffic.

Science.gov (United States)

Horowitz, Arie; Seerapu, Himabindu Reddy

2012-09-01

Recent findings have drawn attention to the role of membrane traffic in the signaling of vascular endothelial growth factor (VEGF). The significance of this development stems from the pivotal function of VEGF in vasculogenesis and angiogenesis. The outline of the regulation of VEGF receptor (VEGFR) signaling by membrane traffic is similar to that of the epidermal growth factor receptor (EGFR), a prototype of the intertwining between membrane traffic and signaling. There are, however, unique features in VEGFR signaling that are conferred in part by the involvement of the co-receptor neuropilin (Nrp). Nrp1 and VEGFR2 are integrated into membrane traffic through the adaptor protein synectin, which recruits myosin VI, a molecular motor that drives inward trafficking [17,21,64]. The recent detection of only mild vascular defects in a knockin mouse model that expresses Nrp1 lacking a cytoplasmic domain [104], questions the co-receptor's role in VEGF signaling and membrane traffic. The regulation of endocytosis by ephrin-B2 is another feature unique to VEGR2/3 [18,19], but it awaits a mechanistic explanation. Current models do not fully explain how membrane traffic bridges between VEGFR and the downstream effectors that produce its functional outcome, such as cell migration. VEGF-A appears to accomplish this task in part by recruiting endocytic vesicles carrying RhoA to internalized active VEGFR2 [58]. Copyright © 2012 Elsevier Inc. All rights reserved.

Uniqueness theorems in linear elasticity

CERN Document Server

Knops, Robin John

1971-01-01

The classical result for uniqueness in elasticity theory is due to Kirchhoff. It states that the standard mixed boundary value problem for a homogeneous isotropic linear elastic material in equilibrium and occupying a bounded three-dimensional region of space possesses at most one solution in the classical sense, provided the Lame and shear moduli, A and J1 respectively, obey the inequalities (3 A + 2 J1) > 0 and J1>O. In linear elastodynamics the analogous result, due to Neumann, is that the initial-mixed boundary value problem possesses at most one solution provided the elastic moduli satisfy the same set of inequalities as in Kirchhoffs theorem. Most standard textbooks on the linear theory of elasticity mention only these two classical criteria for uniqueness and neglect altogether the abundant literature which has appeared since the original publications of Kirchhoff. To remedy this deficiency it seems appropriate to attempt a coherent description ofthe various contributions made to the study of uniquenes...

Using non-invasive molecular spectroscopic techniques to detect unique aspects of protein Amide functional groups and chemical properties of modeled forage from different sourced-origins.

Science.gov (United States)

Ji, Cuiying; Zhang, Xuewei; Yu, Peiqiang

2016-03-05

The non-invasive molecular spectroscopic technique-FT/IR is capable to detect the molecular structure spectral features that are associated with biological, nutritional and biodegradation functions. However, to date, few researches have been conducted to use these non-invasive molecular spectroscopic techniques to study forage internal protein structures associated with biodegradation and biological functions. The objectives of this study were to detect unique aspects and association of protein Amide functional groups in terms of protein Amide I and II spectral profiles and chemical properties in the alfalfa forage (Medicago sativa L.) from different sourced-origins. In this study, alfalfa hay with two different origins was used as modeled forage for molecular structure and chemical property study. In each forage origin, five to seven sources were analyzed. The molecular spectral profiles were determined using FT/IR non-invasive molecular spectroscopy. The parameters of protein spectral profiles included functional groups of Amide I, Amide II and Amide I to II ratio. The results show that the modeled forage Amide I and Amide II were centered at 1653 cm(-1) and 1545 cm(-1), respectively. The Amide I spectral height and area intensities were from 0.02 to 0.03 and 2.67 to 3.36 AI, respectively. The Amide II spectral height and area intensities were from 0.01 to 0.02 and 0.71 to 0.93 AI, respectively. The Amide I to II spectral peak height and area ratios were from 1.86 to 1.88 and 3.68 to 3.79, respectively. Our results show that the non-invasive molecular spectroscopic techniques are capable to detect forage internal protein structure features which are associated with forage chemical properties. Copyright © 2015 Elsevier B.V. All rights reserved.

On uniqueness of an inverse problem in electromagnetic obstacle scattering for an impedance cylinder

International Nuclear Information System (INIS)

Nakamura, Gen; Wang, Haibing; Sleeman, Brian D

2012-01-01

We consider an inverse problem for the scattering of an obliquely incident electromagnetic wave by an impedance cylinder. In previous work, we have shown that the direct scattering problem is governed by a pair of Helmholtz equations subject to coupled oblique boundary conditions, where the wave number depends on the frequency and the incident angle with respect to the axis of the cylinder. In this paper, we are concerned with the inverse problem of uniquely identifying the cross-section of an unknown cylinder and the impedance function from the far-field patterns at fixed frequency and a range of incident angles. A uniqueness result for such an inverse scattering problem is established. Our method is based on the analyticity of solution to the direct scattering problem, which is justified by using the Lax–Phillips method together with the perturbation theory of Fredholm operators. (paper)

A symbol of uniqueness: the cluster bootstrap for the 3-loop MHV heptagon

Energy Technology Data Exchange (ETDEWEB)

Drummond, J.M. [School of Physics & Astronomy, University of Southampton, Highfield, Southampton, SO17 1BJ (United Kingdom); Theory Division, Physics Department, CERN, CH-1211 Geneva 23 (Switzerland); LAPTh, CNRS, Université de Savoie, F-74941 Annecy-le-Vieux Cedex (France); Papathanasiou, G. [LAPTh, CNRS, Université de Savoie, F-74941 Annecy-le-Vieux Cedex (France); Spradlin, M. [Department of Physics, Brown University, Providence, RI 02912 (United States)

2015-03-16

Seven-particle scattering amplitudes in planar super-Yang-Mills theory are believed to belong to a special class of generalised polylogarithm functions called heptagon functions. These are functions with physical branch cuts whose symbols may be written in terms of the 42 cluster A-coordinates on Gr (4,7). Motivated by the success of the hexagon bootstrap programme for constructing six-particle amplitudes we initiate the systematic study of the symbols of heptagon functions. We find that there is exactly one such symbol of weight six which satisfies the MHV last-entry condition and is finite in the 7∥6 collinear limit. This unique symbol is both dihedral and parity-symmetric, and remarkably its collinear limit is exactly the symbol of the three-loop six-particle MHV amplitude, although none of these properties were assumed a priori. It must therefore be the symbol of the three-loop seven-particle MHV amplitude. The simplicity of its construction suggests that the n-gon bootstrap may be surprisingly powerful for n>6.

Origin of the unique ventilatory apparatus of turtles.

Science.gov (United States)

Lyson, Tyler R; Schachner, Emma R; Botha-Brink, Jennifer; Scheyer, Torsten M; Lambertz, Markus; Bever, G S; Rubidge, Bruce S; de Queiroz, Kevin

2014-11-07

The turtle body plan differs markedly from that of other vertebrates and serves as a model system for studying structural and developmental evolution. Incorporation of the ribs into the turtle shell negates the costal movements that effect lung ventilation in other air-breathing amniotes. Instead, turtles have a unique abdominal-muscle-based ventilatory apparatus whose evolutionary origins have remained mysterious. Here we show through broadly comparative anatomical and histological analyses that an early member of the turtle stem lineage has several turtle-specific ventilation characters: rigid ribcage, inferred loss of intercostal muscles and osteological correlates of the primary expiratory muscle. Our results suggest that the ventilation mechanism of turtles evolved through a division of labour between the ribs and muscles of the trunk in which the abdominal muscles took on the primary ventilatory function, whereas the broadened ribs became the primary means of stabilizing the trunk. These changes occurred approximately 50 million years before the evolution of the fully ossified shell.

New Examples of Torsion-Free Non-unique Product Groups

OpenAIRE

Carter, William

2013-01-01

We give an infinite family of torsion-free groups that do not satisfy the unique product property. For these examples, we also show that each group contains arbitrarily large sets whose square has no uniquely represented element.

Early stages of functional diversification in the Rab GTPase gene family revealed by genomic and localization studies in Paramecium species.

Science.gov (United States)

Bright, Lydia J; Gout, Jean-Francois; Lynch, Michael

2017-04-15

New gene functions arise within existing gene families as a result of gene duplication and subsequent diversification. To gain insight into the steps that led to the functional diversification of paralogues, we tracked duplicate retention patterns, expression-level divergence, and subcellular markers of functional diversification in the Rab GTPase gene family in three Paramecium aurelia species. After whole-genome duplication, Rab GTPase duplicates are more highly retained than other genes in the genome but appear to be diverging more rapidly in expression levels, consistent with early steps in functional diversification. However, by localizing specific Rab proteins in Paramecium cells, we found that paralogues from the two most recent whole-genome duplications had virtually identical localization patterns, and that less closely related paralogues showed evidence of both conservation and diversification. The functionally conserved paralogues appear to target to compartments associated with both endocytic and phagocytic recycling functions, confirming evolutionary and functional links between the two pathways in a divergent eukaryotic lineage. Because the functionally diversifying paralogues are still closely related to and derived from a clade of functionally conserved Rab11 genes, we were able to pinpoint three specific amino acid residues that may be driving the change in the localization and thus the function in these proteins. © 2017 Bright et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Identification of unique interactions between the flexible linker and the RecA-like domains of DEAD-box helicase Mss116

International Nuclear Information System (INIS)

Zhang, Yuan; Palla, Mirkó; Liao, Jung-Chi; Sun, Andrew

2013-01-01

DEAD-box RNA helicases are ATP-dependent proteins implicated in nearly all aspects of RNA metabolism. The yeast DEAD-box helicase Mss116 is unique in its functions of splicing group I and group II introns and activating mRNA translation, but the structural understanding of why it performs these unique functions remains unclear. Here we used sequence analysis and molecular dynamics simulation to identify residues in the flexible linker specific for yeast Mss116, potentially associated with its unique functions. We first identified residues that are 100% conserved in Mss116 of different species of the Saccharomycetaceae family. The amino acids of these conserved residues were then compared with the amino acids of the corresponding residue positions of other RNA helicases to identify residues that have distinct amino acids from other DEAD-box proteins. Four residues in the flexible linker, i.e. N334, E335, P336 and H339, are conserved and Mss116-specific. Molecular dynamics simulation was conducted for the wild-type Mss116 structure and mutant models to examine mutational effects of the linker on the conformational equilibrium. Relatively short MD simulation runs (within 20 ns) were enough for us to observe mutational effects, suggesting serious structural perturbations by these mutations. The mutation of E335 depletes the interactions between E335 and K95 in domain 1. The interactions between N334/P336 and N496/I497 of domain 2 are also abolished by mutation. Our results suggest that tight interactions between the Mss116-specific flexible linker and the two RecA-like domains may be mechanically required to crimp RNA for the unique RNA processes of yeast Mss116. (paper)

Identification of unique interactions between the flexible linker and the RecA-like domains of DEAD-box helicase Mss116

Science.gov (United States)

Zhang, Yuan; Palla, Mirkó; Sun, Andrew; Liao, Jung-Chi

2013-09-01

DEAD-box RNA helicases are ATP-dependent proteins implicated in nearly all aspects of RNA metabolism. The yeast DEAD-box helicase Mss116 is unique in its functions of splicing group I and group II introns and activating mRNA translation, but the structural understanding of why it performs these unique functions remains unclear. Here we used sequence analysis and molecular dynamics simulation to identify residues in the flexible linker specific for yeast Mss116, potentially associated with its unique functions. We first identified residues that are 100% conserved in Mss116 of different species of the Saccharomycetaceae family. The amino acids of these conserved residues were then compared with the amino acids of the corresponding residue positions of other RNA helicases to identify residues that have distinct amino acids from other DEAD-box proteins. Four residues in the flexible linker, i.e. N334, E335, P336 and H339, are conserved and Mss116-specific. Molecular dynamics simulation was conducted for the wild-type Mss116 structure and mutant models to examine mutational effects of the linker on the conformational equilibrium. Relatively short MD simulation runs (within 20 ns) were enough for us to observe mutational effects, suggesting serious structural perturbations by these mutations. The mutation of E335 depletes the interactions between E335 and K95 in domain 1. The interactions between N334/P336 and N496/I497 of domain 2 are also abolished by mutation. Our results suggest that tight interactions between the Mss116-specific flexible linker and the two RecA-like domains may be mechanically required to crimp RNA for the unique RNA processes of yeast Mss116.

Unique Perspectives on a Transforming Energy Economy: 2014 Annual Report (Brochure)

Energy Technology Data Exchange (ETDEWEB)

Gossett, S. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

2014-03-01

What makes JISEA unique? Unique perspectives. This brochure highlights the unique perspectives provided by the Joint Institute for Strategic Energy Analysis through JISEA's recent accomplishments and the people behind them.

The dengue vector Aedes aegypti contains a functional high mobility group box 1 (HMGB1 protein with a unique regulatory C-terminus.

Directory of Open Access Journals (Sweden)

Fabio Schneider Ribeiro

Full Text Available The mosquito Aedes aegypti can spread the dengue, chikungunya and yellow fever viruses. Thus, the search for key molecules involved in the mosquito survival represents today a promising vector control strategy. High Mobility Group Box (HMGB proteins are essential nuclear factors that maintain the high-order structure of chromatin, keeping eukaryotic cells viable. Outside the nucleus, secreted HMGB proteins could alert the innate immune system to foreign antigens and trigger the initiation of host defenses. In this work, we cloned and functionally characterized the HMGB1 protein from Aedes aegypti (AaHMGB1. The AaHMGB1 protein typically consists of two HMG-box DNA binding domains and an acidic C-terminus. Interestingly, AaHMGB1 contains a unique alanine/glutamine-rich (AQ-rich C-terminal region that seems to be exclusive of dipteran HMGB proteins. AaHMGB1 is localized to the cell nucleus, mainly associated with heterochromatin. Circular dichroism analyses of AaHMGB1 or the C-terminal truncated proteins revealed α-helical structures. We showed that AaHMGB1 can effectively bind and change the topology of DNA, and that the AQ-rich and the C-terminal acidic regions can modulate its ability to promote DNA supercoiling, as well as its preference to bind supercoiled DNA. AaHMGB1 is phosphorylated by PKA and PKC, but not by CK2. Importantly, phosphorylation of AaHMGB1 by PKA or PKC completely abolishes its DNA bending activity. Thus, our study shows that a functional HMGB1 protein occurs in Aedes aegypt and we provide the first description of a HMGB1 protein containing an AQ-rich regulatory C-terminus.

VEGF induces signalling and angiogenesis by directing VEGFR2 internalisation through macropinocytosis.

Science.gov (United States)

Basagiannis, Dimitris; Zografou, Sofia; Murphy, Carol; Fotsis, Theodore; Morbidelli, Lucia; Ziche, Marina; Bleck, Christopher; Mercer, Jason; Christoforidis, Savvas

2016-11-01

Endocytosis plays a crucial role in receptor signalling. VEGFR2 (also known as KDR) and its ligand VEGFA are fundamental in neovascularisation. However, our understanding of the role of endocytosis in VEGFR2 signalling remains limited. Despite the existence of diverse internalisation routes, the only known endocytic pathway for VEGFR2 is the clathrin-mediated pathway. Here, we show that this pathway is the predominant internalisation route for VEGFR2 only in the absence of ligand. Intriguingly, VEGFA induces a new internalisation itinerary for VEGFR2, the pathway of macropinocytosis, which becomes the prevalent endocytic route for the receptor in the presence of ligand, whereas the contribution of the clathrin-mediated route becomes minor. Macropinocytic internalisation of VEGFR2, which mechanistically is mediated through the small GTPase CDC42, takes place through macropinosomes generated at ruffling areas of the membrane. Interestingly, macropinocytosis plays a crucial role in VEGFA-induced signalling, endothelial cell functions in vitro and angiogenesis in vivo, whereas clathrin-mediated endocytosis is not essential for VEGFA signalling. These findings expand our knowledge on the endocytic pathways of VEGFR2 and suggest that VEGFA-driven internalisation of VEGFR2 through macropinocytosis is essential for endothelial cell signalling and angiogenesis. © 2016. Published by The Company of Biologists Ltd.

PET-CT in the typification of unique pulmonary injuries

International Nuclear Information System (INIS)

Cobos, P.; San Roman, Jose L.; Dalurzo, L.

2007-01-01

The objective of this document is to evaluate the usefulness of the PET-CT for the characterization of the unique pulmonary injuries. Retrospective analysis was made to patients with unique pulmonary injuries who carried out a PET-CT in the Italian Hospital between May of 2003 - March of 2005. Those patients with pulmonary outlying nodule, or unique pulmonary mass that had pathological anatomy of injury or follow-up through a computed tomography of thorax made with an interval of time not minor at 2 years of the PET-CT were included [es

Soluble CD163

DEFF Research Database (Denmark)

Møller, Holger J

2012-01-01

CD163 is an endocytic receptor for haptoglobin-hemoglobin complexes and is expressed solely on macrophages and monocytes. As a result of ectodomain shedding, the extracellular portion of CD163 circulates in blood as a soluble protein (sCD163) at 0.7-3.9 mg/l in healthy individuals. The function o...

Lattices with unique complements

CERN Document Server

Saliĭ, V N

1988-01-01

The class of uniquely complemented lattices properly contains all Boolean lattices. However, no explicit example of a non-Boolean lattice of this class has been found. In addition, the question of whether this class contains any complete non-Boolean lattices remains unanswered. This book focuses on these classical problems of lattice theory and the various attempts to solve them. Requiring no specialized knowledge, the book is directed at researchers and students interested in general algebra and mathematical logic.

On the Uniqueness of Solutions of a Nonlinear Elliptic Problem Arising in the Confinement of a Plasma in a Stellarator Device

International Nuclear Information System (INIS)

Diaz, J. I.; Galiano, G.; Padial, J. F.

1999-01-01

We study the uniqueness of solutions of a semilinear elliptic problem obtained from an inverse formulation when the nonlinear terms of the equation are prescribed in a general class of real functions. The inverse problem arises in the modeling of the magnetic confinement of a plasma in a Stellarator device. The uniqueness proof relies on an L ∞ -estimate on the solution of an auxiliary nonlocal problem formulated in terms of the relative rearrangement of a datum with respect to the solution

Father involvement: Identifying and predicting family members' shared and unique perceptions.

Science.gov (United States)

Dyer, W Justin; Day, Randal D; Harper, James M

2014-08-01

Father involvement research has typically not recognized that reports of involvement contain at least two components: 1 reflecting a view of father involvement that is broadly recognized in the family, and another reflecting each reporter's unique perceptions. Using a longitudinal sample of 302 families, this study provides a first examination of shared and unique views of father involvement (engagement and warmth) from the perspectives of fathers, children, and mothers. This study also identifies influences on these shared and unique perspectives. Father involvement reports were obtained when the child was 12 and 14 years old. Mother reports overlapped more with the shared view than father or child reports. This suggests the mother's view may be more in line with broadly recognized father involvement. Regarding antecedents, for fathers' unique view, a compensatory model partially explains results; that is, negative aspects of family life were positively associated with fathers' unique view. Children's unique view of engagement may partially reflect a sentiment override with father antisocial behaviors being predictive. Mothers' unique view of engagement was predicted by father and mother work hours and her unique view of warmth was predicted by depression and maternal gatekeeping. Taken, together finding suggests a far more nuanced view of father involvement should be considered.

Uniqueness of solutions for a mathematical model for magneto-viscoelastic flows

Science.gov (United States)

Schlömerkemper, A.; Žabenský, J.

2018-06-01

We investigate uniqueness of weak solutions for a system of partial differential equations capturing behavior of magnetoelastic materials. This system couples the Navier–Stokes equations with evolutionary equations for the deformation gradient and for the magnetization obtained from a special case of the micromagnetic energy. It turns out that the conditions on uniqueness coincide with those for the well-known Navier–Stokes equations in bounded domains: weak solutions are unique in two spatial dimensions, and weak solutions satisfying the Prodi–Serrin conditions are unique among all weak solutions in three dimensions. That is, we obtain the so-called weak-strong uniqueness result in three spatial dimensions.

Center for Functional Nanomaterials

Data.gov (United States)

Federal Laboratory Consortium — The Center for Functional Nanomaterials (CFN) explores the unique properties of materials and processes at the nanoscale. The CFN is a user-oriented research center...

Functional derivative of noninteracting kinetic energy density functional

International Nuclear Information System (INIS)

Liu Shubin; Ayers, Paul W.

2004-01-01

Proofs from different theoretical frameworks, namely, the Hohenbergh-Kohn theorems, the Kohn-Sham scheme, and the first-order density matrix representation, have been presented in this paper to show that the functional derivative of the noninteracting kinetic energy density functional can uniquely be expressed as the negative of the Kohn-Sham effective potential, arbitrary only to an additive orbital-independent constant. Key points leading to the current result as well as confusion about the quantity in the literature are briefly discussed

Unique Organization of the Nuclear Envelope in the Post-natal Quiescent Neural Stem Cells

Directory of Open Access Journals (Sweden)

Arantxa Cebrián-Silla

2017-07-01

Full Text Available Neural stem cells (B1 astrocytes; NSCs in the adult ventricular-subventricular-zone (V-SVZ originate in the embryo. Surprisingly, recent work has shown that B1 cells remain largely quiescent. They are reactivated postnatally to function as primary progenitors for neurons destined for the olfactory bulb and some corpus callosum oligodendrocytes. The cellular and molecular properties of quiescent B1 cells remain unknown. Here we found that a subpopulation of B1 cells has a unique nuclear envelope invagination specialization similar to envelope-limited chromatin sheets (ELCS, reported in certain lymphocytes and some cancer cells. Using molecular markers, [3H]thymidine birth-dating, and Ara-C, we found that B1 cells with ELCS correspond to quiescent NSCs. ELCS begin forming in embryonic radial glia cells and represent a specific nuclear compartment containing particular epigenetic modifications and telomeres. These results reveal a unique nuclear compartment in quiescent NSCs, which is useful for identifying these primary progenitors and study their gene regulation.

Affective and cognitive meta-bases of attitudes: Unique effects on information interest and persuasion.

Science.gov (United States)

See, Ya Hui Michelle; Petty, Richard E; Fabrigar, Leandre R

2008-06-01

The authors investigated the predictive utility of people's subjective assessments of whether their evaluations are affect- or cognition driven (i.e., meta-cognitive bases) as separate from whether people's attitudes are actually affect- or cognition based (i.e., structural bases). Study 1 demonstrated that meta-bases uniquely predict interest in affective versus cognitive information above and beyond structural bases and other related variables (i.e., need for cognition and need for affect). In Study 2, meta-bases were shown to account for unique variance in attitude change as a function of appeal type. Finally, Study 3 showed that as people became more deliberative in their judgments, meta-bases increased in predictive utility, and structural bases decreased in predictive utility. These findings support the existence of meta-bases of attitudes and demonstrate that meta-bases are distinguishable from structural bases in their predictive utility. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

Uniqueness of the electrostatic solution in Schwarzschild space

International Nuclear Information System (INIS)

Molnar, Pal G.; Elsaesser, Klaus

2003-01-01

In this Brief Report we give the proof that the solution of any static test charge distribution in Schwarzschild space is unique. In order to give the proof we derive the first Green's identity written with p-forms on (pseudo) Riemannian manifolds. Moreover, the proof of uniqueness can be shown for either any purely electric or purely magnetic field configuration. The spacetime geometry is not crucial for the proof

Anaerobic Ammonium-Oxidizing Bacteria: Unique Microorganisms with Exceptional Properties

Science.gov (United States)

Jetten, Mike S. M.

2012-01-01

Summary: Anaerobic ammonium-oxidizing (anammox) bacteria defy many microbiological concepts and share numerous properties with both eukaryotes and archaea. Among their most intriguing characteristics are their compartmentalized cell plan and archaeon-like cell wall. Here we review our current knowledge about anammox cell biology. The anammox cell is divided into three separate compartments by bilayer membranes. The anammox cell consists of (from outside to inside) the cell wall, paryphoplasm, riboplasm, and anammoxosome. Not much is known about the composition or function of both the anammox cell wall and the paryphoplasm compartment. The cell wall is proposed to be proteinaceous and to lack both peptidoglycan and an outer membrane typical of Gram-negative bacteria. The function of the paryphoplasm is unknown, but it contains the cell division ring. The riboplasm resembles the standard cytoplasmic compartment of other bacteria; it contains ribosomes and the nucleoid. The anammoxosome occupies most of the cell volume and is a so-called “prokaryotic organelle” analogous to the eukaryotic mitochondrion. This is the site where the anammox reaction takes place, coupled over the curved anammoxosome membrane, possibly giving rise to a proton motive force and subsequent ATP synthesis. With these unique properties, anammox bacteria are food for thought concerning the early evolution of the domains Bacteria, Archaea, and Eukarya. PMID:22933561

Entry of Porphyromonas gingivalis Outer Membrane Vesicles into Epithelial Cells Causes Cellular Functional Impairment▿

Science.gov (United States)

Furuta, Nobumichi; Takeuchi, Hiroki; Amano, Atsuo

2009-01-01

Porphyromonas gingivalis, a periodontal pathogen, secretes outer membrane vesicles (MVs) that contain major virulence factors, including proteases termed gingipains (Arg-gingipain [Rgp] and Lys-gingipain [Kgp]). We recently showed that P. gingivalis MVs swiftly enter host epithelial cells via an endocytosis pathway and are finally sorted to lytic compartments. However, it remains unknown whether MV entry impairs cellular function. Herein, we analyzed cellular functional impairment following entry of P. gingivalis into epithelial cells, including HeLa and immortalized human gingival epithelial (IHGE) cells. After being taken up by endocytic vacuoles, MVs degraded the cellular transferrin receptor (TfR) and integrin-related signaling molecules, such as paxillin and focal adhesion kinase (FAK), which resulted in depletion of intracellular transferrin and inhibition of cellular migration. Few Rgp-null MVs entered the cells, and these negligibly degraded TfR, whereas paxillin and FAK degradation was significant. In contrast, Kgp-null MVs clearly entered the cells and degraded TfR, while they scarcely degraded paxillin and FAK. In addition, both wild-type and Kgp-null MVs significantly impaired cellular migration, whereas the effect of Rgp-null MVs was limited. Our findings suggest that, following entry of P. gingivalis MVs into host cells, MV-associated gingipains degrade cellular functional molecules such as TfR and paxillin/FAK, resulting in cellular impairment, indicating that P. gingivalis MVs are potent vehicles for transmission of virulence factors into host cells and are involved in the etiology of periodontitis. PMID:19737899

Comparative developmental psychology: how is human cognitive development unique?

Science.gov (United States)

Rosati, Alexandra G; Wobber, Victoria; Hughes, Kelly; Santos, Laurie R

2014-04-29

The fields of developmental and comparative psychology both seek to illuminate the roots of adult cognitive systems. Developmental studies target the emergence of adult cognitive systems over ontogenetic time, whereas comparative studies investigate the origins of human cognition in our evolutionary history. Despite the long tradition of research in both of these areas, little work has examined the intersection of the two: the study of cognitive development in a comparative perspective. In the current article, we review recent work using this comparative developmental approach to study non-human primate cognition. We argue that comparative data on the pace and pattern of cognitive development across species can address major theoretical questions in both psychology and biology. In particular, such integrative research will allow stronger biological inferences about the function of developmental change, and will be critical in addressing how humans come to acquire species-unique cognitive abilities.

Stability analysis of impulsive functional differential equations

CERN Document Server

Stamova, Ivanka

2009-01-01

This book is devoted to impulsive functional differential equations which are a natural generalization of impulsive ordinary differential equations (without delay) and of functional differential equations (without impulses). At the present time the qualitative theory of such equationsis under rapid development. After a presentation of the fundamental theory of existence, uniqueness and continuability of solutions, a systematic development of stability theory for that class of problems is given which makes the book unique. It addresses to a wide audience such as mathematicians, applied research

Unique, Voltammetric Electrochemical Sensors for Organic Contaminants, with Excellent Discrimination, Based on Conducting Polymer-, Aptamer- and Other-Functionalized Sensing Electrodes, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — In ongoing and recent prior work for the Army, this firm has developed a unique, patented technology for voltammetric electrochemical detection of toxic gases,...

Mannose receptor induces T-cell tolerance via inhibition of CD45 and up-regulation of CTLA-4.

Science.gov (United States)

Schuette, Verena; Embgenbroich, Maria; Ulas, Thomas; Welz, Meike; Schulte-Schrepping, Jonas; Draffehn, Astrid M; Quast, Thomas; Koch, Katharina; Nehring, Melanie; König, Jessica; Zweynert, Annegret; Harms, Frederike L; Steiner, Nancy; Limmer, Andreas; Förster, Irmgard; Berberich-Siebelt, Friederike; Knolle, Percy A; Wohlleber, Dirk; Kolanus, Waldemar; Beyer, Marc; Schultze, Joachim L; Burgdorf, Sven

2016-09-20

The mannose receptor (MR) is an endocytic receptor involved in serum homeostasis and antigen presentation. Here, we identify the MR as a direct regulator of CD8(+) T-cell activity. We demonstrate that MR expression on dendritic cells (DCs) impaired T-cell cytotoxicity in vitro and in vivo. This regulatory effect of the MR was mediated by a direct interaction with CD45 on the T cell, inhibiting its phosphatase activity, which resulted in up-regulation of cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4) and the induction of T-cell tolerance. Inhibition of CD45 prevented expression of B-cell lymphoma 6 (Bcl-6), a transcriptional inhibitor that directly bound the CTLA-4 promoter and regulated its activity. These data demonstrate that endocytic receptors expressed on DCs contribute to the regulation of T-cell functionality.

Functional Impairments in Children with ADHD: Unique Effects of Age and Comorbid Status

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Booster, Genery D.; DuPaul, George J.; Eiraldi, Ricardo; Power, Thomas J.

2012-01-01

Objective: Children with ADHD and comorbid disorders display poorer overall functioning compared with children with ADHD alone, though little research has examined the differential impact of externalizing versus internalizing comorbidities. Method: This study examined the impact of internalizing and externalizing comorbidities on the academic and…

Compartment-specific immunity in the human gut: properties and functions of dendritic cells in the colon versus the ileum.

Science.gov (United States)

Mann, Elizabeth R; Bernardo, David; English, Nicholas R; Landy, Jon; Al-Hassi, Hafid O; Peake, Simon T C; Man, Ripple; Elliott, Timothy R; Spranger, Henning; Lee, Gui Han; Parian, Alyssa; Brant, Steven R; Lazarev, Mark; Hart, Ailsa L; Li, Xuhang; Knight, Stella C

2016-02-01

Dendritic cells (DC) mediate intestinal immune tolerance. Despite striking differences between the colon and the ileum both in function and bacterial load, few studies distinguish between properties of immune cells in these compartments. Furthermore, information of gut DC in humans is scarce. We aimed to characterise human colonic versus ileal DC. Human DC from paired colonic and ileal samples were characterised by flow cytometry, electron microscopy or used to stimulate T cell responses in a mixed leucocyte reaction. A lower proportion of colonic DC produced pro-inflammatory cytokines (tumour necrosis factor-α and interleukin (IL)-1β) compared with their ileal counterparts and exhibited an enhanced ability to generate CD4(+)FoxP3(+)IL-10(+) (regulatory) T cells. There were enhanced proportions of CD103(+)Sirpα(-) DC in the colon, with increased proportions of CD103(+)Sirpα(+) DC in the ileum. A greater proportion of colonic DC subsets analysed expressed the lymph-node-homing marker CCR7, alongside enhanced endocytic capacity, which was most striking in CD103(+)Sirpα(+) DC. Expression of the inhibitory receptor ILT3 was enhanced on colonic DC. Interestingly, endocytic capacity was associated with CD103(+) DC, in particular CD103(+)Sirpα(+) DC. However, expression of ILT3 was associated with CD103(-) DC. Colonic and ileal DC differentially expressed skin-homing marker CCR4 and small-bowel-homing marker CCR9, respectively, and this corresponded to their ability to imprint these homing markers on T cells. The regulatory properties of colonic DC may represent an evolutionary adaptation to the greater bacterial load in the colon. The colon and the ileum should be regarded as separate entities, each comprising DC with distinct roles in mucosal immunity and imprinting. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Multiple floating metatarsals: a unique injury

Directory of Open Access Journals (Sweden)

Trikha Vivek

2013-04-01

Full Text Available 【Abstract】Concomitant dislocation of the tar-sometatarsal and metatarsophalangeal joints of foot is an extremely rare injury. Such injuries presenting in a single or adjacent dual rays have been described in few cases previously. We describe such an injury in adjacent three metatarsals of a polytrauma patient. These injuries are likely to be missed in the initial assessment of a polytrauma patient. These patients are at risk of an overlooked diagnosis but the consequences of missing this type of injury may be Vivek Trikha*, Tarun Goyal, Amit K Agarwal quite severe. This case is presented in view of its unique-ness along with possible mechanism of injury, the sequence of reduction and follow-up. Knowledge of such injury and its proper management may be useful to the trauma surgeons. Key words: Metatarsal bones; Metatarsophalangeal joint; Wounds and injuries

On the Non-Uniqueness of Sediment Yield

Science.gov (United States)

Kim, J.; Ivanov, V. Y.; Fatichi, S.

2014-12-01

There has been ample experimental evidence that soil erosion does not necessarily occur at the same rate, given the same amount of rainfall or runoff. Such a non-unique phenomenon has been often referred to in literature as due to 'natural variability'. Our recent study hypothesized that uncertainties in the distribution and properties of a sediment layer can be a potential clue to one of the reasons of the non-unique sediment yield. Specifically, numerical experimentation with a sophisticated two-dimensional model showed that a deposited layer plays two conflicting roles: it can both increase and decrease soil erosion, given the same magnitude of runoff. The difference in erodibilities of the "original, intact soil layer" and the "deposited, loose soil layer" and the composition of soil particles in the underlying layers give rise to the non-uniqueness of the amount of eroded materials. In continuing efforts, we attempt to investigate this phenomenon using a comprehensive the Universal Soil Loss Erosion (USLE) database, that contains data on paired hillslopes that show a high degree of non-uniqueness in the response, even though the hillslopes exhibit the same topography, soil type, rainfall and meteorological forcings, and landuse. An underlying hypothesis of this study is that uncertainties in the distribution of soil substrate prior to a rainfall event lead to low predictability skill, i.e., a stochastically-varying outcome. A large number of simulation cases demonstrating the proposed hypothesis are conducted using a coupled numerical model, tRIBS-VEGGIE-FEaST (Triangulated irregular network - based Real time Integrated Basin Simulator- VEGetation Generator for Interactive Evolution -Flow Erosion and Sediment Transport).

Accessibility of physical states and non-uniqueness of entanglement measure

International Nuclear Information System (INIS)

Morikoshi, Fumiaki; Santos, Marcelo Franca; Vedral, Vlatko

2004-01-01

Ordering physical states is the key to quantifying some physical property of the states uniquely. Bipartite pure entangled states are totally ordered under local operations and classical communication (LOCC) in the asymptotic limit and uniquely quantified by the well-known entropy of entanglement. However, we show that mixed entangled states are partially ordered under LOCC even in the asymptotic limit. Therefore, non-uniqueness of entanglement measure is understood on the basis of an operational notion of asymptotic convertibility

Cognitive Prediction of Reading, Math, and Attention: Shared and Unique Influences.

Science.gov (United States)

Peterson, Robin L; Boada, Richard; McGrath, Lauren M; Willcutt, Erik G; Olson, Richard K; Pennington, Bruce F

The current study tested a multiple-cognitive predictor model of word reading, math ability, and attention in a community-based sample of twins ages 8 to 16 years ( N = 636). The objective was to identify cognitive predictors unique to each skill domain as well as cognitive predictors shared among skills that could help explain their overlap and thus help illuminate the basis for comorbidity of related disorders (reading disability, math disability, and attention deficit hyperactivity disorder). Results indicated that processing speed contributes to the overlap between reading and attention as well as math and attention, whereas verbal comprehension contributes to the overlap between reading and math. There was no evidence that executive functioning skills help account for covariation among these skill domains. Instead, specific executive functions differentially related to certain outcomes (i.e., working memory to math and inhibition to attention). We explored whether the model varied in younger versus older children and found only minor differences. Results are interpreted within the context of the multiple deficit framework for neurodevelopmental disorders.

Host cell virus entry mediated by Australian bat lyssavirus G envelope glycoprotein occurs through a clathrin-mediated endocytic pathway that requires actin and Rab5.

Science.gov (United States)

Weir, Dawn L; Laing, Eric D; Smith, Ina L; Wang, Lin-Fa; Broder, Christopher C

2014-02-27

Australian bat lyssavirus (ABLV), a rhabdovirus of the genus Lyssavirus which circulates in both pteropid fruit bats and insectivorous bats in mainland Australia, has caused three fatal human infections, the most recent in February 2013, manifested as acute neurological disease indistinguishable from clinical rabies. Rhabdoviruses infect host cells through receptor-mediated endocytosis and subsequent pH-dependent fusion mediated by their single envelope glycoprotein (G), but the specific host factors and pathways involved in ABLV entry have not been determined. ABLV internalization into HEK293T cells was examined using maxGFP-encoding recombinant vesicular stomatitis viruses (rVSV) that express ABLV G glycoproteins. A combination of chemical and molecular approaches was used to investigate the contribution of different endocytic pathways to ABLV entry. Dominant negative Rab GTPases were used to identify the endosomal compartment utilized by ABLV to gain entry into the host cell cytosol. Here we show that ABLV G-mediated entry into HEK293T cells was significantly inhibited by the dynamin-specific inhibitor dynasore, chlorpromazine, a drug that blocks clathrin-mediated endocytosis, and the actin depolymerizing drug latrunculin B. Over expression of dominant negative mutants of Eps15 and Rab5 also significantly reduced ABLV G-mediated entry into HEK293T cells. Chemical inhibitors of caveolae-dependent endocytosis and macropinocytosis and dominant negative mutants of Rab7 and Rab11 had no effect on ABLV entry. The predominant pathway utilized by ABLV for internalization into HEK293T cells is clathrin-and actin-dependent. The requirement of Rab5 for productive infection indicates that ABLV G-mediated fusion occurs within the early endosome compartment.

Consciousness: a unique way of processing information.

Science.gov (United States)

Marchetti, Giorgio

2018-02-08

In this article, I argue that consciousness is a unique way of processing information, in that: it produces information, rather than purely transmitting it; the information it produces is meaningful for us; the meaning it has is always individuated. This uniqueness allows us to process information on the basis of our personal needs and ever-changing interactions with the environment, and consequently to act autonomously. Three main basic cognitive processes contribute to realize this unique way of information processing: the self, attention and working memory. The self, which is primarily expressed via the central and peripheral nervous systems, maps our body, the environment, and our relations with the environment. It is the primary means by which the complexity inherent to our composite structure is reduced into the "single voice" of a unique individual. It provides a reference system that (albeit evolving) is sufficiently stable to define the variations that will be used as the raw material for the construction of conscious information. Attention allows for the selection of those variations in the state of the self that are most relevant in the given situation. Attention originates and is deployed from a single locus inside our body, which represents the center of the self, around which all our conscious experiences are organized. Whatever is focused by attention appears in our consciousness as possessing a spatial quality defined by this center and the direction toward which attention is focused. In addition, attention determines two other features of conscious experience: periodicity and phenomenal quality. Self and attention are necessary but not sufficient for conscious information to be produced. Complex forms of conscious experiences, such as the various modes of givenness of conscious experience and the stream of consciousness, need a working memory mechanism to assemble the basic pieces of information selected by attention.

Numb endocytic adapter proteins regulate the transport and processing of the amyloid precursor protein in an isoform-dependent manner: implications for Alzheimer disease pathogenesis.

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Kyriazis, George A; Wei, Zelan; Vandermey, Miriam; Jo, Dong-Gyu; Xin, Ouyang; Mattson, Mark P; Chan, Sic L

2008-09-12

Central to the pathogenesis of Alzheimer disease is the aberrant processing of the amyloid precursor protein (APP) to generate amyloid beta-peptide (Abeta), the principle component of amyloid plaques. The cell fate determinant Numb is a phosphotyrosine binding domain (PTB)-containing endocytic adapter protein that interacts with the carboxyl-terminal domain of APP. The physiological relevance of this interaction is unknown. Mammals produce four alternatively spliced variants of Numb that differ in the length of their PTB and proline-rich region. In the current study, we determined the influence of the four human Numb isoforms on the intracellular trafficking and processing of APP. Stable expression of Numb isoforms that differ in the PTB but not in the proline-rich region results in marked differences in the sorting of APP to the recycling and degradative pathways. Neural cells expressing Numb isoforms that lack the insert in the PTB (short PTB (SPTB)) exhibited marked accumulation of APP in Rab5A-labeled early endosomal and recycling compartments, whereas those expressing isoforms with the insertion in the PTB (long PTB (LPTB)) exhibited reduced amounts of cellular APP and its proteolytic derivatives relative to parental control cells. Neither the activities of the beta- and gamma-secretases nor the expression of APP mRNA were significantly different in the stably transfected cells, suggesting that the differential effects of the Numb proteins on APP metabolism is likely to be secondary to altered APP trafficking. In addition, the expression of SPTB-Numb increases at the expense of LPTB-Numb in neuronal cultures subjected to stress, suggesting a role for Numb in stress-induced Abeta production. Taken together, these results suggest distinct roles for the human Numb isoforms in APP metabolism and may provide a novel potential link between altered Numb isoform expression and increased Abeta generation.

Human Papillomavirus 16 Infection Induces VAP-Dependent Endosomal Tubulation.

Science.gov (United States)

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

Cellullar insights into cerebral cortical development: focusing on the locomotion mode of neuronal migration

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Takeshi eKawauchi

2015-10-01

Full Text Available The mammalian brain consists of numerous compartments that are closely connected with each other via neural networks, comprising the basis of higher order brain functions. The highly specialized structure originates from simple pseudostratified neuroepithelium-derived neural progenitors located near the ventricle. A long journey by neurons from the ventricular side is essential for the formation of a sophisticated brain structure, including a mammalian-specific six-layered cerebral cortex. Neuronal migration consists of several contiguous steps, but the locomotion mode comprises a large part of the migration. The locomoting neurons exhibit unique features; a radial glial fiber-dependent migration requiring the endocytic recycling of N-cadherin and a neuron-specific migration mode with dilation/swelling formation that requires the actin and microtubule organization possibly regulated by cyclin-dependent kinase 5 (Cdk5, Dcx, p27kip1, Rac1 and POSH. Here I will introduce the roles of various cellular events, such as cytoskeletal organization, cell adhesion and membrane trafficking, in the regulation of the neuronal migration, with particular focus on the locomotion mode.

Weeping dragon, a unique ornamenal citrus

Science.gov (United States)

‘Weeping Dragon’ is a new ornamental citrus cultivar developed by intercrossing of two unusual and unique citrus types, Poncirus trifoliata cultivated variety (cv.) Flying Dragon, and Citrus sinensis cv. ‘Cipo’. This new hybrid cultivar combines strongly contorted and weeping growth traits in a smal...

Unique coexistence of dispersion stability and nanoparticle chemisorption in alkylamine/alkylacid encapsulated silver nanocolloids.

Science.gov (United States)

Aoshima, Keisuke; Hirakawa, Yuya; Togashi, Takanari; Kurihara, Masato; Arai, Shunto; Hasegawa, Tatsuo

2018-04-17

Surface encapsulation of metal nanoparticles (NPs) is fundamental to achieve sufficient dispersion stability of metal nanocolloids, or metal nanoink. However, the feature is incompatible with surface reactive nature of the metal NPs, although these features are both essential to realizing the functional applications into printed electronics technologies. Here we show that two different kinds of encapsulation for silver NPs (AgNPs) by alkylamine and alkylacid together are the key to achieve unique compatibility between the high dispersion stability as dense nanoclolloids and the AgNP chemisorption printing on activated patterned polymer surfaces. Advanced confocal dynamic light scattering study reveals that an additive trace amount of oleic acid is the critical parameter for controlling the dispersion and coagulative (or surface-reactive) characteristics of the silver nanocolloids. The composition of the disperse media is also important for obtaining highly concentrated but low-viscosity silver nanocolloids that show very stable dispersion. The results demonstrate that the high-resolution AgNP chemisorption printing is possible only by using unique silver nanocolloids composed of an exceptional balance of ligand formulation and dispersant composition.

IL4/PGE2 induction of an enlarged early endosomal compartment in mouse macrophages is Rab5-dependent

International Nuclear Information System (INIS)

Wainszelbaum, Marisa J.; Proctor, Brandon M.; Pontow, Suzanne E.; Stahl, Philip D.; Barbieri, M. Alejandro

2006-01-01

The endosomal compartment and the plasma membrane form a complex partnership that controls signal transduction and trafficking of different molecules. The specificity and functionality of the early endocytic pathway are regulated by a growing number of Rab GTPases, particularly Rab5. In this study, we demonstrate that IL4 (a Th-2 cytokine) and prostaglandin E 2 (PGE 2 ) synergistically induce Rab5 and several Rab effector proteins, including Rin1 and EEA1, and promote the formation of an enlarged early endocytic (EEE) compartment. Endosome enlargement is linked to a substantial induction of the mannose receptor (MR), a well-characterized macrophage endocytic receptor. Both MR levels and MR-mediated endocytosis are enhanced approximately 7-fold. Fluid-phase endocytosis is also elevated in treated cells. Light microscopy and fractionation studies reveal that MR colocalizes predominantly with Rab5a and partially with Rab11, an endosomal recycling pathway marker. Using retroviral expression of Rab5a:S34N, a dominant negative mutant, and siRNA Rab5a silencing, we demonstrate that Rab5a is essential for the large endosome phenotype and for localization of MR in these structures. We speculate that the EEE is maintained by activated Rab5, and that the EEE phenotype is part of some macrophage developmental program such as cell fusion, a characteristic of IL4-stimulated cells

On uniqueness in evolution quasivariational inequalities

Czech Academy of Sciences Publication Activity Database

Brokate, M.; Krejčí, Pavel; Schnabel, H.

2004-01-01

Roč. 11, č. 1 (2004), s. 111-130 ISSN 0944-6532 Institutional research plan: CEZ:AV0Z1019905 Keywords : evolution quasivariational inequality * uniqueness * sweeping process Subject RIV: BA - General Mathematics Impact factor: 0.425, year: 2004 http://www.heldermann-verlag.de/jca/jca11/jca0386.pdf

Membrane Transport across Polarized Epithelia.

Science.gov (United States)

Garcia-Castillo, Maria Daniela; Chinnapen, Daniel J-F; Lencer, Wayne I

2017-09-01

Polarized epithelial cells line diverse surfaces throughout the body forming selective barriers between the external environment and the internal milieu. To cross these epithelial barriers, large solutes and other cargoes must undergo transcytosis, an endocytic pathway unique to polarized cell types, and significant for the development of cell polarity, uptake of viral and bacterial pathogens, transepithelial signaling, and immunoglobulin transport. Here, we review recent advances in our knowledge of the transcytotic pathway for proteins and lipids. We also discuss briefly the promise of harnessing the molecules that undergo transcytosis as vehicles for clinical applications in drug delivery. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Holistic Leadership-Nursing's Unique Contribution to Healthcare.

Science.gov (United States)

Clarke, Pamela N; Bleich, Michael R

2018-04-01

This dialogue is focused on holistic leadership from the perspective of a well-known leader in nursing. He frames the changing healthcare environment and nursing's unique contribution on the interprofessional team.

48 CFR 52.211-7 - Alternatives to Government-unique standards.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Alternatives to Government... Government-unique standards. The offeror may propose voluntary consensus standards that meet the Government's... voluntary consensus standard instead of the Government-unique standard if it meets the Government's...

Functional mesoporous silica nanoparticles for bio-imaging applications.

Science.gov (United States)

Cha, Bong Geun; Kim, Jaeyun

2018-03-22

Biomedical investigations using mesoporous silica nanoparticles (MSNs) have received significant attention because of their unique properties including controllable mesoporous structure, high specific surface area, large pore volume, and tunable particle size. These unique features make MSNs suitable for simultaneous diagnosis and therapy with unique advantages to encapsulate and load a variety of therapeutic agents, deliver these agents to the desired location, and release the drugs in a controlled manner. Among various clinical areas, nanomaterials-based bio-imaging techniques have advanced rapidly with the development of diverse functional nanoparticles. Due to the unique features of MSNs, an imaging agent supported by MSNs can be a promising system for developing targeted bio-imaging contrast agents with high structural stability and enhanced functionality that enable imaging of various modalities. Here, we review the recent achievements on the development of functional MSNs for bio-imaging applications, including optical imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), ultrasound imaging, and multimodal imaging for early diagnosis. With further improvement in noninvasive bio-imaging techniques, the MSN-supported imaging agent systems are expected to contribute to clinical applications in the future. This article is categorized under: Diagnostic Tools > In vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology. © 2018 Wiley Periodicals, Inc.

UNiquant, a Program for Quantitative Proteomics Analysis Using Stable Isotope Labeling

Energy Technology Data Exchange (ETDEWEB)

Huang, Xin; Tolmachev, Aleksey V.; Shen, Yulei; Liu, Miao; Huang, Lin; Zhang, Zhixin; Anderson, Gordon A.; Smith, Richard D.; Chan, Wing C.; Hinrichs, Steven; Fu, Kai; Ding, Shi-Jian

2011-03-04

We present UNiquant, a new software program for analyzing stable isotope labeling (SIL) based quantitative proteomics data. UNiquant surpassed the performance of two other platforms, MaxQuant and Mascot Distiller, using complex proteome mixtures having either known or unknown heavy/light ratios. UNiquant is compatible with a broad spectrum of search engines and SIL methods, providing outstanding peptide pair identification and accurate measurement of the relative peptide/protein abundance.

Fluorescent Photo-conversion: A second chance to label unique cells.

Science.gov (United States)

Mellott, Adam J; Shinogle, Heather E; Moore, David S; Detamore, Michael S

2015-03-01

Not all cells behave uniformly after treatment in tissue engineering studies. In fact, some treated cells display no signs of treatment or show unique characteristics not consistent with other treated cells. What if the "unique" cells could be isolated from a treated population, and further studied? Photo-convertible reporter proteins, such as Dendra2 , allow for the ability to selectively identify unique cells with a secondary label within a primary labeled treated population. In the current study, select cells were identified and labeled through photo-conversion of Dendra2 -transfected human Wharton's Jelly cells (hWJCs) for the first time. Robust photo-conversion of green-to-red fluorescence was achieved consistently in arbitrarily selected cells, allowing for precise cell identification of select hWJCs. The current study demonstrates a method that offers investigators the opportunity to selectively label and identify unique cells within a treated population for further study or isolation from the treatment population. Photo-convertible reporter proteins, such as Dendra2 , offer the ability over non-photo-convertible reporter proteins, such as green fluorescent protein, to analyze unique individual cells within a treated population, which allows investigators to gain more meaningful information on how a treatment affects all cells within a target population.

Functional genomics unique to week 20 post wounding in the deep cone/fat dome of the Duroc/Yorkshire porcine model of fibroproliferative scarring.

Science.gov (United States)

Engrav, Loren H; Tuggle, Christopher K; Kerr, Kathleen F; Zhu, Kathy Q; Numhom, Surawej; Couture, Oliver P; Beyer, Richard P; Hocking, Anne M; Carrougher, Gretchen J; Ramos, Maria Luiza C; Klein, Matthew B; Gibran, Nicole S

2011-04-20

Hypertrophic scar was first described over 100 years ago; PubMed has more than 1,000 references on the topic. Nevertheless prevention and treatment remains poor, because 1) there has been no validated animal model; 2) human scar tissue, which is impossible to obtain in a controlled manner, has been the only source for study; 3) tissues typically have been homogenized, mixing cell populations; and 4) gene-by-gene studies are incomplete. We have assembled a system that overcomes these barriers and permits the study of genome-wide gene expression in microanatomical locations, in shallow and deep partial-thickness wounds, and pigmented and non-pigmented skin, using the Duroc(pigmented fibroproliferative)/Yorkshire(non-pigmented non-fibroproliferative) porcine model. We used this system to obtain the differential transcriptome at 1, 2, 3, 12 and 20 weeks post wounding. It is not clear when fibroproliferation begins, but it is fully developed in humans and the Duroc breed at 20 weeks. Therefore we obtained the derivative functional genomics unique to 20 weeks post wounding. We also obtained long-term, forty-six week follow-up with the model. 1) The scars are still thick at forty-six weeks post wounding further validating the model. 2) The differential transcriptome provides new insights into the fibroproliferative process as several genes thought fundamental to fibroproliferation are absent and others differentially expressed are newly implicated. 3) The findings in the derivative functional genomics support old concepts, which further validates the model, and suggests new avenues for reductionist exploration. In the future, these findings will be searched for directed networks likely involved in cutaneous fibroproliferation. These clues may lead to a better understanding of the systems biology of cutaneous fibroproliferation, and ultimately prevention and treatment of hypertrophic scarring.

Functional genomics unique to week 20 post wounding in the deep cone/fat dome of the Duroc/Yorkshire porcine model of fibroproliferative scarring.

Directory of Open Access Journals (Sweden)

Loren H Engrav

Full Text Available BACKGROUND: Hypertrophic scar was first described over 100 years ago; PubMed has more than 1,000 references on the topic. Nevertheless prevention and treatment remains poor, because 1 there has been no validated animal model; 2 human scar tissue, which is impossible to obtain in a controlled manner, has been the only source for study; 3 tissues typically have been homogenized, mixing cell populations; and 4 gene-by-gene studies are incomplete. METHODOLOGY/PRINCIPAL FINDINGS: We have assembled a system that overcomes these barriers and permits the study of genome-wide gene expression in microanatomical locations, in shallow and deep partial-thickness wounds, and pigmented and non-pigmented skin, using the Duroc(pigmented fibroproliferative/Yorkshire(non-pigmented non-fibroproliferative porcine model. We used this system to obtain the differential transcriptome at 1, 2, 3, 12 and 20 weeks post wounding. It is not clear when fibroproliferation begins, but it is fully developed in humans and the Duroc breed at 20 weeks. Therefore we obtained the derivative functional genomics unique to 20 weeks post wounding. We also obtained long-term, forty-six week follow-up with the model. CONCLUSIONS/SIGNIFICANCE: 1 The scars are still thick at forty-six weeks post wounding further validating the model. 2 The differential transcriptome provides new insights into the fibroproliferative process as several genes thought fundamental to fibroproliferation are absent and others differentially expressed are newly implicated. 3 The findings in the derivative functional genomics support old concepts, which further validates the model, and suggests new avenues for reductionist exploration. In the future, these findings will be searched for directed networks likely involved in cutaneous fibroproliferation. These clues may lead to a better understanding of the systems biology of cutaneous fibroproliferation, and ultimately prevention and treatment of hypertrophic scarring.

From flexibility to function: Molecular dynamics simulations of conformational changes in chaperones and photoreceptors

NARCIS (Netherlands)

Singhal, K.

2016-01-01

Proteins are uniquely-shaped macromolecules that function as biological machines, and regulate a living cell’s behavior. Crucial to protein function is the folding of the polypeptide chain into a unique well-defined three-dimensional conformation. In complex cell environments, the spontaneous

Losing memories overnight: a unique form of human amnesia.

Science.gov (United States)

Smith, Christine N; Frascino, Jennifer C; Kripke, Donald L; McHugh, Paul R; Treisman, Glenn J; Squire, Larry R

2010-08-01

Since an automobile accident in 2005, patient FL has reported difficulty retaining information from one day to the next. During the course of any given day, she describes her memory as normal. However, memory for each day disappears during a night of sleep. She reports good memory for events that occurred before the accident. Although this pattern of memory impairment is, to our knowledge, unique to the medical literature, it was depicted in the fictional film "50 First Dates". On formal testing, FL performed moderately well when trying to remember material that she had learned during the same day, but she exhibited no memory at all for material that she knew had been presented on a previous day. For some tests, unbeknownst to FL, material learned on the previous day was intermixed with material learned on the same day as the test. On these occasions, FL's memory was good. Thus, she was able to remember events from earlier days when memory was tested covertly. FL performed differently in a number of ways from individuals who were instructed to consciously feign her pattern of memory impairment. It was also the impression of those who worked with FL that she believed she had the memory impairment that she described and that she was not intentionally feigning amnesia. On the basis of her neuropsychological findings, together with a normal neurological exam, normal MRI findings, and psychiatric evaluation, we suggest that FL exhibits a unique form of functional amnesia and that its characterization may have been influenced by knowledge of how amnesia was depicted in a popular film. She subsequently improved (and began retaining day-to-day memory) at Johns Hopkins University where she was in a supportive in-patient environment and was shown how to take control of her condition by interrupting her sleep at 4-h intervals. Published by Elsevier Ltd.

Denture identification using unique identification authority of India barcode

OpenAIRE

Sudhindra Mahoorkar; Anoop Jain

2013-01-01

Over the years, various denture marking systems have been reported in the literature for personal identification. They have been broadly divided into surface marking and inclusion methods. In this technique, patient's unique identification number and barcode printed in the patient's Aadhaar card issued by Unique Identification Authority of India (UIDAI) are used as denture markers. This article describes a simple, quick, and economical method for identification of individual.

Denture identification using unique identification authority of India barcode.

Science.gov (United States)

Mahoorkar, Sudhindra; Jain, Anoop

2013-01-01

Over the years, various denture marking systems have been reported in the literature for personal identification. They have been broadly divided into surface marking and inclusion methods. In this technique, patient's unique identification number and barcode printed in the patient's Aadhaar card issued by Unique Identification Authority of India (UIDAI) are used as denture markers. This article describes a simple, quick, and economical method for identification of individual.

The N-terminal domains of Vps3 and Vps8 are critical for localization and function of the CORVET tethering complex on endosomes.

Directory of Open Access Journals (Sweden)

Nadine Epp

Full Text Available Endosomal biogenesis depends on multiple fusion and fission events. For fusion, the heterohexameric CORVET complex as an effector of the endosomal Rab5/Vps21 GTPase has a central function in the initial tethering event. Here, we show that the CORVET-specific Vps3 and Vps8 subunits, which interact with Rab5/Vps21, require their N-terminal domains for localization and function. Surprisingly, CORVET may lack either one of the two N-terminal domains, but not both, to promote protein sorting via the endosome. The dually truncated complex mislocalizes to the cytosol and is impaired in endocytic protein sorting, but not in assembly. Furthermore, the endosomal localization can be rescued by overexpression of Vps21 or one of the truncated CORVET subunits, even though CORVET assembly is not impaired by loss of the N-terminal domains or in strains lacking all endosomal Rab5s and Ypt7. We thus conclude that CORVET requires only its C-terminal domains for assembly and has beyond its putative β-propeller domains additional binding sites for endosomes, which could be important to bind Vps21 and other endosome-specific factors for efficient endosome tethering.

On the uniqueness of minimizers for a class of variational problems with Polyconvex integrand

KAUST Repository

Awi, Romeo

2017-02-05

We prove existence and uniqueness of minimizers for a family of energy functionals that arises in Elasticity and involves polyconvex integrands over a certain subset of displacement maps. This work extends previous results by Awi and Gangbo to a larger class of integrands. First, we study these variational problems over displacements for which the determinant is positive. Second, we consider a limit case in which the functionals are degenerate. In that case, the set of admissible displacements reduces to that of incompressible displacements which are measure preserving maps. Finally, we establish that the minimizer over the set of incompressible maps may be obtained as a limit of minimizers corresponding to a sequence of minimization problems over general displacements provided we have enough regularity on the dual problems. We point out that these results defy the direct methods of the calculus of variations.

Evolution PDEs with nonstandard growth conditions existence, uniqueness, localization, blow-up

CERN Document Server

Antontsev, Stanislav

2015-01-01

This monograph offers the reader a treatment of the theory of evolution PDEs with nonstandard growth conditions. This class includes parabolic and hyperbolic equations with variable or anisotropic nonlinear structure. We develop methods for the study of such equations and present a detailed account of recent results. An overview of other approaches to the study of PDEs of this kind is provided. The presentation is focused on the issues of existence and uniqueness of solutions in appropriate function spaces, and on the study of the specific qualitative properties of solutions, such as localization in space and time, extinction in a finite time and blow-up, or nonexistence of global in time solutions. Special attention is paid to the study of the properties intrinsic to solutions of equations with nonstandard growth.

Lightness functions

DEFF Research Database (Denmark)

Campi, Stefano; Gardner, Richard; Gronchi, Paolo

2012-01-01

Variants of the brightness function of a convex body K in n-dimensional Euclidean are investigated. The Lambertian lightness function L(K; v , w ) gives the total reflected light resulting from illumination by a light source at infinity in the direction w that is visible when looking...... in the direction v . The partial brightness function R( K ; v , w ) gives the area of the projection orthogonal to v of the portion of the surface of K that is both illuminated by a light source from the direction w and visible when looking in the direction v . A class of functions called lightness functions...... is introduced that includes L(K;.) and R(K;.) as special cases. Much of the theory of the brightness function like uniqueness, stability, and the existence and properties of convex bodies of maximal and minimal volume with finitely many function values equal to those of a given convex body, is extended...

Flexible and efficient genome tiling design with penalized uniqueness score

Directory of Open Access Journals (Sweden)

Du Yang

2012-12-01

Full Text Available Abstract Background As a powerful tool in whole genome analysis, tiling array has been widely used in the answering of many genomic questions. Now it could also serve as a capture device for the library preparation in the popular high throughput sequencing experiments. Thus, a flexible and efficient tiling array design approach is still needed and could assist in various types and scales of transcriptomic experiment. Results In this paper, we address issues and challenges in designing probes suitable for tiling array applications and targeted sequencing. In particular, we define the penalized uniqueness score, which serves as a controlling criterion to eliminate potential cross-hybridization, and a flexible tiling array design pipeline. Unlike BLAST or simple suffix array based methods, computing and using our uniqueness measurement can be more efficient for large scale design and require less memory. The parameters provided could assist in various types of genomic tiling task. In addition, using both commercial array data and experiment data we show, unlike previously claimed, that palindromic sequence exhibiting relatively lower uniqueness. Conclusions Our proposed penalized uniqueness score could serve as a better indicator for cross hybridization with higher sensitivity and specificity, giving more control of expected array quality. The flexible tiling design algorithm incorporating the penalized uniqueness score was shown to give higher coverage and resolution. The package to calculate the penalized uniqueness score and the described probe selection algorithm are implemented as a Perl program, which is freely available at http://www1.fbn-dummerstorf.de/en/forschung/fbs/fb3/paper/2012-yang-1/OTAD.v1.1.tar.gz.

Unique Neural Characteristics of Atypical Lateralization of Language in Healthy Individuals

Directory of Open Access Journals (Sweden)

Szymon P. Biduła

2017-09-01

Full Text Available Using functional magnetic resonance imaging (fMRI in 63 healthy participants, including left-handed and ambidextrous individuals, we tested how atypical lateralization of language—i. e., bilateral or right hemispheric language representation—differs from the typical left-hemisphere dominance. Although regardless of their handedness, all 11 participants from the atypical group engaged classical language centers, i.e., Broca's and Wernicke's areas, the right-hemisphere components of the default mode network (DMN, including the angular gyrus and middle temporal gyrus, were also critically involved during the verbal fluency task. Importantly, activity in these regions could not be explained in terms of mirroring the typical language pattern because left-hemisphere dominant individuals did not exhibit similar significant signal modulations. Moreover, when spatial extent of language-related activity across whole brain was considered, the bilateral language organization entailed more diffuse functional processing. Finally, we detected significant differences between the typical and atypical group in the resting-state connectivity at the global and local level. These findings suggest that the atypical lateralization of language has unique features, and is not a simple mirror image of the typical left hemispheric language representation.

Convergent Synthesis of Piperidines by the Union of Conjugated Alkynes with Imines: A Unique Regioselective Bond Construction for Heterocycle Synthesis

Science.gov (United States)

Chen, Ming Z.; Micalizio, Glenn C.

2009-01-01

A two-step process is described for the union of aromatic imines, conjugated alkynes and aldehydes that results in a stereoselective synthesis of highly substituted piperidines. This synthetic process has been made possible by defining a unique regioselective functionalization of conjugated alkynes that establishes a suitably functionalized substrate for subsequent heterocycle-forming cationic annulation. Given the flexibility of the coupling process, heterocycles can be accessed through a process that establishes up to four stereogenic centers and four fused rings. PMID:19817447

Guide to good practices for operations aspects of unique processes

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-12-01

This Guide to Good Practices is written to enhance understanding of, and provide direction for, Operations Aspects of Facility Chemistry and Unique Processes, Chapter XIII of Department of Energy (DOE) Order 5480.19, Conduct of Operations Requirements for DOE Facilities. The practices in this guide should be considered when planning or reviewing employee training and facility management programs. Contractors are advised to adopt procedures that meet the intent of DOE Order 5480.19. Operations Aspects of Unique Processes is an element of an effective Conduct of Operations program. The complexity and array of activities performed in DOE facilities dictate the necessity for all personnel to coordinate interrelated activities affecting unique processes.

Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo

Science.gov (United States)

He, Qianchuan; Madsen, Mette; Kilkenney, Adam; Gregory, Brittany; Christensen, Erik I.; Vorum, Henrik; Højrup, Peter; Schäffer, Alejandro A.; Kirkness, Ewen F.; Tanner, Stephan M.; de la Chapelle, Albert; Giger, Urs; Moestrup, Søren K.; Fyfe, John C.

2005-01-01

Amnionless (AMN) and cubilin gene products appear to be essential functional subunits of an endocytic receptor called cubam. Mutation of either gene causes autosomal recessive Imerslund-Gräsbeck syndrome (I-GS, OMIM no. 261100) in humans, a disorder characterized by selective intestinal malabsorption of cobalamin (vitamin B12) and urinary loss of several specific low-molecular-weight proteins. Vital insight into the molecular pathology of I-GS has been obtained from studies of dogs with a similar syndrome. In this work, we show that I-GS segregates in a large canine kindred due to an in-frame deletion of 33 nucleotides in exon 10 of AMN. In a second, unrelated I-GS kindred, affected dogs exhibit a homozygous substitution in the AMN translation initiation codon. Studies in vivo demonstrated that both mutations abrogate AMN expression and block cubilin processing and targeting to the apical membrane. The essential features of AMN dysfunction observed in vivo are recapitulated in a heterologous cell-transfection system, thus validating the system for analysis of AMN-cubilin interactions. Characterization of canine AMN mutations that cause I-GS establishes the canine model as an ortholog of the human disorder well suited to studies of AMN function and coevolution with cubilin. (Blood. 2005;106:1447-1453) PMID:15845892

Unique proteomic signatures distinguish macrophages and dendritic cells.

Directory of Open Access Journals (Sweden)

Lev Becker

Full Text Available Monocytes differentiate into heterogeneous populations of tissue macrophages and dendritic cells (DCs that regulate inflammation and immunity. Identifying specific populations of myeloid cells in vivo is problematic, however, because only a limited number of proteins have been used to assign cellular phenotype. Using mass spectrometry and bone marrow-derived cells, we provided a global view of the proteomes of M-CSF-derived macrophages, classically and alternatively activated macrophages, and GM-CSF-derived DCs. Remarkably, the expression levels of half the plasma membrane proteins differed significantly in the various populations of cells derived in vitro. Moreover, the membrane proteomes of macrophages and DCs were more distinct than those of classically and alternatively activated macrophages. Hierarchical cluster and dual statistical analyses demonstrated that each cell type exhibited a robust proteomic signature that was unique. To interrogate the phenotype of myeloid cells in vivo, we subjected elicited peritoneal macrophages harvested from wild-type and GM-CSF-deficient mice to mass spectrometric and functional analysis. Unexpectedly, we found that peritoneal macrophages exhibited many features of the DCs generated in vitro. These findings demonstrate that global analysis of the membrane proteome can help define immune cell phenotypes in vivo.

The product of capacities and belief functions

DEFF Research Database (Denmark)

Hendon, Ebbe; Whitta-Jacobsen, Hans Jørgen; Sloth, Birgitte

1996-01-01

Capacities (monotone, non-additive set functions) have been suggested to describe situations of uncertainty. We examine the question of how to define the product of two independent capacities. In particular, for the product of two belief functions (totally monotone capacities), there is a unique...... minimal product belief function. This is characterized in several ways...

The product of capacities and belief functions

DEFF Research Database (Denmark)

Hendon, Ebbe; Jacobsen, Hans Jørgen; Sloth, Birgitte

1996-01-01

Capacities (monotone, non-additive set functions) have been suggested to describe situations of uncertainty. We examine the question of how to define the product of two independent capacities. In particular, for the product of two belief functions (totally monotone capacities), there is a unique...... minimal product belief function. This is characterized in several ways....

Staphylococcal enterotoxin-like X (SElX is a unique superantigen with functional features of two major families of staphylococcal virulence factors.

Directory of Open Access Journals (Sweden)

Ries J Langley

2017-09-01

Full Text Available Staphylococcus aureus is an opportunistic pathogen that produces many virulence factors. Two major families of which are the staphylococcal superantigens (SAgs and the Staphylococcal Superantigen-Like (SSL exoproteins. The former are immunomodulatory toxins that induce a Vβ-specific activation of T cells, while the latter are immune evasion molecules that interfere with a wide range of innate immune defences. The superantigenic properties of Staphylococcal enterotoxin-like X (SElX have recently been established. We now reveal that SElX also possesses functional characteristics of the SSLs. A region of SElX displays high homology to the sialyl-lactosamine (sLacNac-specific binding site present in a sub-family of SSLs. By analysing the interaction of SElX with sLacNac-containing glycans we show that SElX has an equivalent specificity and host cell binding range to the SSLs. Mutation of key amino acids in this conserved region affects the ability of SElX to bind to cells of myeloid origin and significantly reduces its ability to protect S. aureus from destruction in a whole blood killing (WBK assay. Like the SSLs, SElX is up-regulated early during infection and is under the control of the S. aureus exotoxin expression (Sae two component gene regulatory system. Additionally, the structure of SElX in complex with the sLacNac-containing tetrasaccharide sialyl Lewis X (sLeX reveals that SElX is a unique single-domain SAg. In summary, SElX is an 'SSL-like' SAg.

Unique structure and optics of the lesser eyes of the box jellyfish Tripedalia cystophora

DEFF Research Database (Denmark)

Garm, A; Andersson, F; Nilsson, Dan-E

2008-01-01

mere light meters. The slit eyes, comprising four cell types, are complex and highly asymmetric. They also hold a lens-like structure, but its optical power is minute. Optical modeling suggests spatial resolution, but only in one plane. These unique and intriguing traits support strong peripheral......The visual system of box jellyfish comprises a total of 24 eyes. These are of four types and each probably has a special function. To investigate this hypothesis the morphology and optics of the lesser eyes, the pit and slit eyes, were examined. The pit eyes hold one cell type only and are probably...

Pain and executive functions: A unique relationship between Stroop task and experimentally induced pain

NARCIS (Netherlands)

Bjekic, J.; Zivanovic, M.; Puric, D.; Oosterman, J.M.; Filipovic, S.R.

2018-01-01

There is a growing body of evidence that a higher level of cognitive inhibition is associated with lower experimental pain sensitivity. However, a systematic examination of the association between executive functions, which include not only inhibition but also updating and shifting, and experimental

Boundary value problems of finite elasticity local theorems on existence, uniqueness, and analytic dependence on data

CERN Document Server

Valent, Tullio

1988-01-01

In this book I present, in a systematic form, some local theorems on existence, uniqueness, and analytic dependence on the load, which I have recently obtained for some types of boundary value problems of finite elasticity. Actually, these results concern an n-dimensional (n ~ 1) formal generalization of three-dimensional elasticity. Such a generalization, be­ sides being quite spontaneous, allows us to consider a great many inter­ esting mathematical situations, and sometimes allows us to clarify certain aspects of the three-dimensional case. Part of the matter presented is unpublished; other arguments have been only partially published and in lesser generality. Note that I concentrate on simultaneous local existence and uniqueness; thus, I do not deal with the more general theory of exis­ tence. Moreover, I restrict my discussion to compressible elastic bodies and I do not treat unilateral problems. The clever use of the inverse function theorem in finite elasticity made by STOPPELLI [1954, 1957a, 1957b]...

The Uniqueness of Milton Friedman

OpenAIRE

J. Daniel Hammond

2013-01-01

That there is no Milton Friedman today is not a mystery; the mystery is how Milton Friedman could have been. The facts of Friedman’s biography make him unique among twentieth-century public figures. He had extensive knowledge and expertise in mathematics and statistics. Yet he became a critic of ‘formal’ theory, exemplified by mathematical economics, that failed to engage with real-world facts and data, and of econometric modeling that presumed more knowledge of economic structure than Friedm...

High Blood Pressure: Unique to Older Adults

Science.gov (United States)

... our e-newsletter! Aging & Health A to Z High Blood Pressure Hypertension Unique to Older Adults This section provides ... Pressure Targets are Different for Very Old Adults High blood pressure (also called hypertension) increases your chance of having ...

The Hydrologic Implications Of Unique Urban Soil Horizon Sequencing On The Functions Of Passive Green Infrastructure

Science.gov (United States)

Shuster, W.; Schifman, L. A.; Herrmann, D.

2017-12-01

Green infrastructure represents a broad set of site- to landscape-scale practices that can be flexibly implemented to increase sewershed retention capacity, and can thereby improve on the management of water quantity and quality. Although much green infrastructure presents as formal engineered designs, urbanized landscapes with highly-interspersed pervious surfaces (e.g., right-of-way, parks, lawns, vacant land) may offer ecosystem services as passive, infiltrative green infrastructure. Yet, infiltration and drainage processes are regulated by soil surface conditions, and then the layering of subsoil horizons, respectively. Drawing on a unique urban soil taxonomic and hydrologic dataset collected in 12 cities (each city representing a major soil order), we determined how urbanization processes altered the sequence of soil horizons (compared to pre-urbanized reference soil pedons) and modeled the hydrologic implications of these shifts in layering with an unsaturated zone code (HYDRUS2D). We found that the different layering sequences in urbanized soils render different types and extents of supporting (plant-available soil water), provisioning (productive vegetation), and regulating (runoff mitigation) ecosystem services.

Functional Independence in Late-Life: Maintaining Physical Functioning in Older Adulthood Predicts Daily Life Function after Age 80.

Science.gov (United States)

Vaughan, Leslie; Leng, Xiaoyan; La Monte, Michael J; Tindle, Hilary A; Cochrane, Barbara B; Shumaker, Sally A

2016-03-01

We examined physical functioning (PF) trajectories (maintaining, slowly declining, and rapidly declining) spanning 15 years in older women aged 65-80 and protective factors that predicted better current levels and less decline in functional independence outcomes after age 80. Women's Health Initiative extension participants who met criteria (enrolled in either the clinical trial or observational study cohort, >80 years at the data release cutoff, PF survey data from initial enrollment to age 80, and functional independence survey data after age 80) were included in these analyses (mean [SD] age = 84.0 [1.4] years; N = 10,478). PF was measured with the SF-36 (mean = 4.9 occasions). Functional independence was measured by self-reported level of dependence in basic and instrumental activities of daily living (ADLs and IADLs) (mean = 3.4 and 3.3 occasions). Maintaining consistent PF in older adulthood extends functional independence in ADL and IADL in late-life. Protective factors shared by ADL and IADL include maintaining PF over time, self-reported excellent or very good health, no history of hip fracture after age 55, and no history of cardiovascular disease. Better IADL function is uniquely predicted by a body mass index less than 25 and no depression. Less ADL and IADL decline is predicted by better self-reported health, and less IADL decline is uniquely predicted by having no history of hip fracture after age 55. Maintaining or improving PF and preventing injury and disease in older adulthood (ages 65-80) has far-reaching implications for improving late-life (after age 80) functional independence. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Unique Protein Signature of Circulating Microparticles in Systemic Lupus Erythematosus

DEFF Research Database (Denmark)

Østergaard, Ole; Nielsen, Christoffer; Iversen, Line V

2013-01-01

To characterize the unique qualities of proteins associated with circulating subcellular material in systemic lupus erythematosus (SLE) patients compared with healthy controls and patients with other chronic autoimmune diseases.......To characterize the unique qualities of proteins associated with circulating subcellular material in systemic lupus erythematosus (SLE) patients compared with healthy controls and patients with other chronic autoimmune diseases....

Cytotoxic protein from the mushroom Coprinus comatus possesses a unique mode for glycan binding and specificity.

Science.gov (United States)

Zhang, Peilan; Li, Kunhua; Yang, Guang; Xia, Changqing; Polston, Jane E; Li, Gengnan; Li, Shiwu; Lin, Zhao; Yang, Li-Jun; Bruner, Steven D; Ding, Yousong

2017-08-22

Glycans possess significant chemical diversity; glycan binding proteins (GBPs) recognize specific glycans to translate their structures to functions in various physiological and pathological processes. Therefore, the discovery and characterization of novel GBPs and characterization of glycan-GBP interactions are significant to provide potential targets for therapeutic intervention of many diseases. Here, we report the biochemical, functional, and structural characterization of a 130-amino-acid protein, Y3, from the mushroom Coprinus comatus Biochemical studies of recombinant Y3 from a yeast expression system demonstrated the protein is a unique GBP. Additionally, we show that Y3 exhibits selective and potent cytotoxicity toward human T-cell leukemia Jurkat cells compared with a panel of cancer cell lines via inducing caspase-dependent apoptosis. Screening of a glycan array demonstrated GalNAcβ1-4(Fucα1-3)GlcNAc (LDNF) as a specific Y3-binding ligand. To provide a structural basis for function, the crystal structure was solved to a resolution of 1.2 Å, revealing a single-domain αβα-sandwich motif. Two monomers were dimerized to form a large 10-stranded, antiparallel β-sheet flanked by α-helices on each side, representing a unique oligomerization mode among GBPs. A large glycan binding pocket extends into the dimeric interface, and docking of LDNF identified key residues for glycan interactions. Disruption of residues predicted to be involved in LDNF/Y3 interactions resulted in the significant loss of binding to Jurkat T-cells and severely impaired their cytotoxicity. Collectively, these results demonstrate Y3 to be a GBP with selective cytotoxicity toward human T-cell leukemia cells and indicate its potential use in cancer diagnosis and treatment.

Physical uniqueness of higher-order Korteweg-de Vries theory for continuously stratified fluids without background shear

Science.gov (United States)

Shimizu, Kenji

2017-10-01

The 2nd-order Korteweg-de Vries (KdV) equation and the Gardner (or extended KdV) equation are often used to investigate internal solitary waves, commonly observed in oceans and lakes. However, application of these KdV-type equations for continuously stratified fluids to geophysical problems is hindered by nonuniqueness of the higher-order coefficients and the associated correction functions to the wave fields. This study proposes to reduce arbitrariness of the higher-order KdV theory by considering its uniqueness in the following three physical senses: (i) consistency of the nonlinear higher-order coefficients and correction functions with the corresponding phase speeds, (ii) wavenumber-independence of the vertically integrated available potential energy, and (iii) its positive definiteness. The spectral (or generalized Fourier) approach based on vertical modes in the isopycnal coordinate is shown to enable an alternative derivation of the 2nd-order KdV equation, without encountering nonuniqueness. Comparison with previous theories shows that Parseval's theorem naturally yields a unique set of special conditions for (ii) and (iii). Hydrostatic fully nonlinear solutions, derived by combining the spectral approach and simple-wave analysis, reveal that both proposed and previous 2nd-order theories satisfy (i), provided that consistent definitions are used for the wave amplitude and the nonlinear correction. This condition reduces the arbitrariness when higher-order KdV-type theories are compared with observations or numerical simulations. The coefficients and correction functions that satisfy (i)-(iii) are given by explicit formulae to 2nd order and by algebraic recurrence relationships to arbitrary order for hydrostatic fully nonlinear and linear fully nonhydrostatic effects.

Ubiquitin-Mediated Regulation of Endocytosis by Proteins of the Arrestin Family

Directory of Open Access Journals (Sweden)

Michel Becuwe

2012-01-01

Full Text Available In metazoans, proteins of the arrestin family are key players of G-protein-coupled receptors (GPCRS signaling and trafficking. Following stimulation, activated receptors are phosphorylated, thus allowing the binding of arrestins and hence an “arrest” of receptor signaling. Arrestins act by uncoupling receptors from G proteins and contribute to the recruitment of endocytic proteins, such as clathrin, to direct receptor trafficking into the endocytic pathway. Arrestins also serve as adaptor proteins by promoting the recruitment of ubiquitin ligases and participate in the agonist-induced ubiquitylation of receptors, known to have impact on their subcellular localization and stability. Recently, the arrestin family has expanded following the discovery of arrestin-related proteins in other eukaryotes such as yeasts or fungi. Surprisingly, most of these proteins are also involved in the ubiquitylation and endocytosis of plasma membrane proteins, thus suggesting that the role of arrestins as ubiquitin ligase adaptors is at the core of these proteins' functions. Importantly, arrestins are themselves ubiquitylated, and this modification is crucial for their function. In this paper, we discuss recent data on the intricate connections between arrestins and the ubiquitin pathway in the control of endocytosis.

Shedding light on the role of lipid flippases in the secretory pathway

DEFF Research Database (Denmark)

Lopez Marques, Rosa Laura

that these pumps serve important functions in vesicular traffic, their activities being required to support vesicle formation in the secretory and endocytic pathways. We are now aiming at determining the mechanism by which these ATPases function in vesicle biogenesis. For this purpose, we are using novel...... biophysical approaches based on giant vesicles and several advanced bioimaging methods. The limitations and future perspectives of these techniques for the characterization of lipid translocases will be discussed in the light of our recent results....

Revealing a steroid receptor ligand as a unique PPAR[gamma] agonist

Energy Technology Data Exchange (ETDEWEB)

Lin, Shengchen; Han, Ying; Shi, Yuzhe; Rong, Hui; Zheng, Songyang; Jin, Shikan; Lin, Shu-Yong; Lin, Sheng-Cai; Li, Yong (Pitt); (Xiamen)

2012-06-28

Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) regulates metabolic homeostasis and is a molecular target for anti-diabetic drugs. We report here the identification of a steroid receptor ligand, RU-486, as an unexpected PPAR{gamma} agonist, thereby uncovering a novel signaling route for this steroid drug. Similar to rosiglitazone, RU-486 modulates the expression of key PPAR{gamma} target genes and promotes adipocyte differentiation, but with a lower adipogenic activity. Structural and functional studies of receptor-ligand interactions reveal the molecular basis for a unique binding mode for RU-486 in the PPAR{gamma} ligand-binding pocket with distinctive properties and epitopes, providing the molecular mechanisms for the discrimination of RU-486 from thiazolidinediones (TZDs) drugs. Our findings together indicate that steroid compounds may represent an alternative approach for designing non-TZD PPAR{gamma} ligands in the treatment of insulin resistance.

Unique spin-polarized transmission effects in a QD ring structure

Science.gov (United States)

Hedin, Eric; Joe, Yong

2010-10-01

Spintronics is an emerging field in which the spin of the electron is used for switching purposes and to communicate information. In order to obtain spin-polarized electron transmission, the Zeeman effect is employed to produce spin-split energy states in quantum dots which are embedded in the arms of a mesoscopic Aharonov-Bohm (AB) ring heterostructure. The Zeeman splitting of the QD energy levels can be induced by a parallel magnetic field, or by a perpendicular field which also produces AB-effects. The combination of these effects on the transmission resonances of the structure is studied analytically and several parameter regimes are identified which produce a high degree of spin-polarized output. Contour and line plots of the weighted spin polarization as a function of electron energy and magnetic field are presented to visualize the degree of spin-polarization. Taking advantage of these unique parameter regimes shows the potential promise of such devices for producing spin-polarized currents.

Word from the CSO - CERN’s unique scientific breadth

CERN Multimedia

2008-01-01

Whilst we are all clearly focused on completion of the LHC and the detectors around it and look forward to a successful start of operations later this year, we should not forget that CERN has yet more to offer in addition to this highest priority programme ‘at the energy frontier’. Indeed, CERN also attracts a large scientific community seizing the opportunities offered by its other facilities. Sometimes I wonder whether we are not too modest and should not emphasize more CERN’s unique scientific breadth. ISOLDE, at the PS Booster, relies on innovative techniques to produce results at the forefront of nuclear physics very cost-effectively. nTOF has provided unique measurements of interest to nuclear technology, nuclear astrophysics and basic nuclear physics, and still has an ambitious programme ahead of it after refurbishment of the target. Another unique facility is the Antiproton Decelerator, at which the study of antimatter is being pursued with ingenious experiment...

Duality based direct resolution of unique profiles using zero concentration region information.

Science.gov (United States)

Tavakkoli, Elnaz; Rajkó, Róbert; Abdollahi, Hamid

2018-07-01

Self Modeling Curve Resolution (SMCR) is a class of techniques concerned with estimating pure profiles underlying a set of measurements on chemical systems. In general, the estimated profiles are ambiguous (non-unique) except if some special conditions fulfilled. Implementing the adequate information can reduce the so-called rotational ambiguity effectively, and in the most desirable cases lead to the unique solution. Therefore, studies on circumstances resulting in unique solution are of particular importance. The conditions of unique solution can particularly be studied based on duality principle. In bilinear chemical (e.g., spectroscopic) data matrix, there is a natural duality between its row and column vector spaces using minimal constraints (non-negativity of concentrations and absorbances). In this article, the conditions of the unique solution according to duality concept and using zero concentration region information is intended to show. A simulated dataset of three components and an experimental system with synthetic mixtures containing three amino acids tyrosine, phenylalanine and tryptophan are analyzed. It is shown that in the presence of sufficient information, the reliable unique solution is obtained that is valuable in analytical qualification and for quantitative verification analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

The end of the unique myocardial band

DEFF Research Database (Denmark)

MacIver, David H; Partridge, John B; Agger, Peter

2018-01-01

Two of the leading concepts of mural ventricular architecture are the unique myocardial band and the myocardial mesh model. We have described, in an accompanying article published in this journal, how the anatomical, histological and high-resolution computed tomographic studies strongly favour th...

Unique neurobiology during the sensitive period for attachment produces distinctive infant trauma processing

Science.gov (United States)

Opendak, Maya; Sullivan, Regina M.

2016-01-01

Background Trauma has neurobehavioral effects when experienced at any stage of development, but trauma experienced in early life has unique neurobehavioral outcomes related to later life psychiatric sequelae. Recent evidence has further highlighted the context of infant trauma as a critical variable in determining its immediate and enduring consequences. Trauma experienced from an attachment figure, such as occurs in cases of caregiver child maltreatment, is particularly detrimental. Methods Using data primarily from rodent models, we review the literature on the interaction between trauma and attachment in early life, which highlights the role of the caregiver’s presence in engagement of attachment brain circuitry and suppressing threat processing by the amygdala. We then consider how trauma with and without the caregiver produces long-term changes in emotionality and behavior, and suggest that these experiences initiate distinct pathways to pathology. Results Together these data suggest that infant trauma processing and its enduring effects are impacted by both the immaturity of brain areas for processing trauma and the unique functioning of the early-life brain, which is biased toward processing information within the attachment circuitry. Conclusion An understanding of developmental differences in trauma processing as well as the critical role of the caregiver in further altering early life brain processing of trauma is important for developing age-relevant treatment and interventions. Highlights of this article Trauma experienced in early life has been linked with life-long outcomes for mental health through a mechanism that remains unclear. Trauma experienced in the presence of a caregiver has unique consequences. The infant brain is predisposed toward processing information using attachment circuitry rather than threat circuitry. Data from rodent models suggest that repeated trauma in the presence of a caregiver prematurely engages brain areas important

46-kDa protein located in the flagellar pocket of Leishmania ...

Indian Academy of Sciences (India)

NII

Cloning and expression of endocytic Rab GTPases from Leishmania. Fractionation of early compartment from. Leishmania containing endocytic probes. Rab7:WT. Rab5: WT. Localization of Rab5 and Rab7 in Leishmania. Phase. LTR. Merge. Rab7-GFP. Rab5-GFP. LTR. Phase. Merge. Rab5-GFP. Rab7-GFP. Lysosomes.

The function of introns

Directory of Open Access Journals (Sweden)

Liran eCarmel

2012-04-01

Full Text Available The intron-exon architecture of many eukaryotic genes raises the intriguing question of whether this unique organization serves any function, or is it simply a result of the spread of functionless introns in eukaryotic genomes. In this review, we show that introns in contemporary species fulfill a broad spectrum of functions, and are involved in virtually every step of mRNA processing. We propose that this great diversity of intronic functions supports the notion that introns were indeed selfish elements in early eukaryotes, but then independently gained numerous functions in different eukaryotic lineages. We suggest a novel criterion of evolutionary conservation, dubbed intron positional conservation, which can identify functional introns.

Concentration and mindfulness meditations: unique forms of consciousness?

Science.gov (United States)

Dunn, B R; Hartigan, J A; Mikulas, W L

1999-09-01

Electroencephalographic (EEG) recordings from 19 scalp recording sites were used to differentiate among two posited unique forms of mediation, concentration and mindfulness, and a normal relaxation control condition. Analyzes of all traditional frequency bandwidth data (i.e., delta 1-3 Hz; theta, 4-7 Hz; alpha, 8-12 Hz; beta 1, 13-25 Hz; beta 2, 26-32 Hz) showed strong mean amplitude frequency differences between the two meditation conditions and relaxation over numerous cortical sites. Furthermore, significant differences were obtained between concentration and mindfulness states at all bandwidths. Taken together, our results suggest that concentration and mindfulness "meditations" may be unique forms of consciousness and are not merely degrees of a state of relaxation.

Solitary intraosseous neurofibroma: Report of a unique case

Directory of Open Access Journals (Sweden)

Sagar Satish Jangam

2014-01-01

Full Text Available Neural tumors located centrally in jaw bones are relatively rare compared with soft tissue neurofibromas. Less than 50 cases have been reported in the literature with a predilection for mandible. This article aims to elucidate a unique case of intraosseous neurofibroma of mandible in a 62-year-old edentulous female patient associated with facial asymmetry due to the swelling extending from the right body of mandible to left body of mandible. The uniqueness of this case is related to the age and extensiveness of this lesion. A review of clinical, radiographic, histological, and immunohistochemical features, and the surgical management pertaining to this case are discussed along with a review of the literature.

The RTR complex as caretaker of genome stability and its unique meiotic function in plants

Directory of Open Access Journals (Sweden)

Alexander eKnoll

2014-02-01

Full Text Available The RTR complex consisting of a RecQ helicase, a type IA topoisomerase and the structural protein RMI1 is involved in the processing of DNA recombination intermediates in all eukaryotes. In Arabidopsis thaliana the complex partners RECQ4A, topoisomerase 3α and RMI1 have been shown to be involved in DNA repair and in the suppression of homologous recombination (HR in somatic cells. Interestingly, mutants of AtTOP3A and AtRMI1 are also sterile due to extensive chromosome breakage in meiosis I, a phenotype that seems to be specific for plants. Although both proteins are essential for meiotic recombination it is still elusive on what kind of intermediates they are acting on. Recent data indicate that the pattern of non-crossover (NCO-associated meiotic gene conversion (GC differs between plants and other eukaryotes, as less NCOs in comparison to crossovers (CO could be detected in Arabidopsis. This indicates that NCOs happen either more rarely in plants or that the conversion tract length is significantly shorter than in other organisms. As the TOP3α/RMI1-mediated dissolution of recombination intermediates results exclusively in NCOs, we suggest that the peculiar GC pattern found in plants is connected to the unique role, members of the RTR complex play in plant meiosis.

Unique Features of Halophilic Proteins.

Science.gov (United States)

Arakawa, Tsutomu; Yamaguchi, Rui; Tokunaga, Hiroko; Tokunaga, Masao

2017-01-01

Proteins from moderate and extreme halophiles have unique characteristics. They are highly acidic and hydrophilic, similar to intrinsically disordered proteins. These characteristics make the halophilic proteins soluble in water and fold reversibly. In addition to reversible folding, the rate of refolding of halophilic proteins from denatured structure is generally slow, often taking several days, for example, for extremely halophilic proteins. This slow folding rate makes the halophilic proteins a novel model system for folding mechanism analysis. High solubility and reversible folding also make the halophilic proteins excellent fusion partners for soluble expression of recombinant proteins.

Unique microstructure and excellent mechanical properties of ADI

Directory of Open Access Journals (Sweden)

Jincheng Liu

2006-11-01

Full Text Available Amongst the cast iron family, ADI has a unique microstructure and an excellent, optimised combination of mechanical properties. The main microstructure of ADI is ausferrite, which is a mixture ofextremely fine acicular ferrite and stable, high carbon austenite. There are two types of austenite in ADI:(1 the coarser and more equiaxed blocks of austenite between non-parallel acicular structures, which exist mainly in the last solidified area, and (2 the thin films of ustenite between the individual ferriteplatelets in the acicular structure. It is this unique microstructure, which gives ADI its excellent static and dynamic properties, and good low temperature impact toughness. The effect of microstructure on the mechanical properties is explained in more detail by examining the microstructure at the atomic scale. Considering the nanometer grain sizes, the unique microstructure, the excellent mechanical properties,good castability, (which enables near net shape components to be produced economically and in large volumes, and the fact that it can be 100% recycled, it is not overemphasized to call ADI a high-tech,nanometer and “green” material. ADI still has the potential to be further improved and its production and the number of applications for ADI will continue to grow, driven by the resultant cost savings over alternative materials.

Plant ion channels: gene families, physiology, and functional genomics analyses.

Science.gov (United States)

Ward, John M; Mäser, Pascal; Schroeder, Julian I

2009-01-01

Distinct potassium, anion, and calcium channels in the plasma membrane and vacuolar membrane of plant cells have been identified and characterized by patch clamping. Primarily owing to advances in Arabidopsis genetics and genomics, and yeast functional complementation, many of the corresponding genes have been identified. Recent advances in our understanding of ion channel genes that mediate signal transduction and ion transport are discussed here. Some plant ion channels, for example, ALMT and SLAC anion channel subunits, are unique. The majority of plant ion channel families exhibit homology to animal genes; such families include both hyperpolarization- and depolarization-activated Shaker-type potassium channels, CLC chloride transporters/channels, cyclic nucleotide-gated channels, and ionotropic glutamate receptor homologs. These plant ion channels offer unique opportunities to analyze the structural mechanisms and functions of ion channels. Here we review gene families of selected plant ion channel classes and discuss unique structure-function aspects and their physiological roles in plant cell signaling and transport.

Operations Between Functions

DEFF Research Database (Denmark)

Gardner, Richard J.; Kiderlen, Markus

A structural theory of operations between real-valued (or extended-real-valued) functions on a nonempty subset A of Rn is initiated. It is shown, for example, that any operation ∗ on a cone of functions containing the constant functions, which is pointwise, positively homogeneous, monotonic......, and associative, must be one of 40 explicitly given types. In particular, this is the case for operations between pairs of arbitrary, or continuous, or differentiable functions. The term pointwise means that (f ∗g)(x) = F(f(x), g(x)), for all x ∈ A and some function F of two variables. Several results in the same...... spirit are obtained for operations between convex functions or between support functions. For example, it is shown that ordinary addition is the unique pointwise operation between convex functions satisfying the identity property, i.e., f ∗ 0 = 0 ∗ f = f, for all convex f, while other results classify Lp...

A Role for EHD4 in the Regulation of Early Endosomal Transport

Science.gov (United States)

Sharma, Mahak; Naslavsky, Naava; Caplan, Steve

2009-01-01

All four of the C-terminal Eps15 homology domain (EHD) proteins have been implicated in the regulation of endocytic trafficking. However, the high level of amino acid sequence identity among these proteins has made it challenging to elucidate the precise function of individual EHD proteins. We demonstrate here with specific peptide antibodies that endogenous EHD4 localizes to Rab5-, early embryonic antigen 1 (EEA1)- and Arf6-containing endosomes and colocalizes with internalized transferrin in the cell periphery. Knock-down of EHD4 expression by both small interfering RNA and short hairpin RNA leads to the generation of enlarged early endosomal structures that contain Rab5 and EEA1 as well as internalized transferrin or major histocompatibility complex class I molecules. In addition, cargo destined for degradation, such as internalized low-density lipoprotein, also accumulates in the enlarged early endosomes in EHD4-depleted cells. Moreover, we have demonstrated that these enlarged early endosomes are enriched in levels of the activated GTP-bound Rab5. Finally, we show that endogenous EHD4 and EHD1 interact in cells, suggesting coordinated involvement in the regulation of receptor transport along the early endosome to endocytic recycling compartment axis. The results presented herein provide evidence that EHD4 is involved in the control of trafficking at the early endosome and regulates exit of cargo toward both the recycling compartment and the late endocytic pathway. PMID:18331452

A unique deubiquitinase that deconjugates phosphoribosyl-linked protein ubiquitination

Energy Technology Data Exchange (ETDEWEB)

Qiu, Jiazhang; Yu, Kaiwen; Fei, Xiaowen; Liu, Yao; Nakayasu, Ernesto S.; Piehowski, Paul D.; Shaw, Jared B.; Puvar, Kedar; Das, Chittaranjan; Liu, Xiaoyun; Luo, Zhao-Qing

2017-05-12

Ubiquitination regulates many aspects of host immunity and thus is a common target for infectious agents. Recent studies revealed that members of the SidE effector family of the bacterial pathogen Legionella pneumophila attacked several small GTPases associated with the endoplasmic reticulum by a novel ubiquitination mechanism that does not require the E1 and E2 enzymes of the host ubiquitination machinery. Following ubiquitin activation by ADP- ribosylation via a mono-ADP-ribosylation motif, ADP-ribosylated ubiquitin is cleaved by a phosphodiesterasedomainwithinSdeA,whichisconcomitantwiththelinkof phosphoribosylated ubiquitin to serine residues in the substrate. Here we demonstrate that the activity of SidEs is regulated by SidJ, another effector encoded by a gene situated in the locus coding for three members of the SidE family (SdeC, SdeB and SdeA). SidJ functions to remove ubiquitin from SidEs-modified substrates by cleaving the phosphodiester bond that links phosphoribosylated ubiquitin to protein substrates. Further, the deubiquitinase activity of SidJ is essential for its role in L. pneumophila infection. Finally, the activity of SidJ is required for efficiently reducing the abundance of ubiquitinated Rab33b in infected cells within a few hours after bacterial uptake. Our results establish SidJ as a deubiquitinase that functions to impose temporal regulation of the activity of the SidE effectors. The identification of SidJ may shed light on future study of signaling cascades mediated by this unique ubiquitination that also potentially regulates cellular processes in eukaryotic cells.

Intracellular Route of Canine Parvovirus Entry

Science.gov (United States)

Vihinen-Ranta, Maija; Kalela, Anne; Mäkinen, Päivi; Kakkola, Laura; Marjomäki, Varpu; Vuento, Matti

1998-01-01

The present study was designed to investigate the endocytic pathway involved in canine parvovirus (CPV) infection. Reduced temperature (18°C) or the microtubule-depolymerizing drug nocodazole was found to inhibit productive infection of canine A72 cells by CPV and caused CPV to be retained in cytoplasmic vesicles as indicated by immunofluorescence microscopy. Consistent with previously published results, these data indicate that CPV enters a host cell via an endocytic route and further suggest that microtubule-dependent delivery of CPV to late endosomes is required for productive infection. Cytoplasmic microinjection of CPV particles was used to circumvent the endocytosis and membrane fusion steps in the entry process. Microinjection experiments showed that CPV particles which were injected directly into the cytoplasm, thus avoiding the endocytic pathway, were unable to initiate progeny virus production. CPV treated at pH 5.0 prior to microinjection was unable to initiate virus production, showing that factors of the endocytic route other than low pH are necessary for the initiation of infection by CPV. PMID:9420290

Functional microbiology of soda lakes

NARCIS (Netherlands)

Sorokin, D.Y.; Banciu, H.L.; Muyzer, G.

2015-01-01

Soda lakes represent unique permanently haloalkaline system. Despite the harsh conditions, they are inhabited by abundant, mostly prokaryotic, microbial communities. This review summarizes results of studies of main functional groups of the soda lake prokaryotes responsible for carbon, nitrogen and

Skipper genome sheds light on unique phenotypic traits and phylogeny.

Science.gov (United States)

Cong, Qian; Borek, Dominika; Otwinowski, Zbyszek; Grishin, Nick V

2015-08-27

Butterflies and moths are emerging as model organisms in genetics and evolutionary studies. The family Hesperiidae (skippers) was traditionally viewed as a sister to other butterflies based on its moth-like morphology and darting flight habits with fast wing beats. However, DNA studies suggest that the family Papilionidae (swallowtails) may be the sister to other butterflies including skippers. The moth-like features and the controversial position of skippers in Lepidoptera phylogeny make them valuable targets for comparative genomics. We obtained the 310 Mb draft genome of the Clouded Skipper (Lerema accius) from a wild-caught specimen using a cost-effective strategy that overcomes the high (1.6 %) heterozygosity problem. Comparative analysis of Lerema accius and the highly heterozygous genome of Papilio glaucus revealed differences in patterns of SNP distribution, but similarities in functions of genes that are enriched in non-synonymous SNPs. Comparison of Lepidoptera genomes revealed possible molecular bases for unique traits of skippers: a duplication of electron transport chain components could result in efficient energy supply for their rapid flight; a diversified family of predicted cellulases might allow them to feed on cellulose-enriched grasses; an expansion of pheromone-binding proteins and enzymes for pheromone synthesis implies a more efficient mate-recognition system, which compensates for the lack of clear visual cues due to the similarities in wing colors and patterns of many species of skippers. Phylogenetic analysis of several Lepidoptera genomes suggested that the position of Hesperiidae remains uncertain as the tree topology varied depending on the evolutionary model. Completion of the first genome from the family Hesperiidae allowed comparative analyses with other Lepidoptera that revealed potential genetic bases for the unique phenotypic traits of skippers. This work lays the foundation for future experimental studies of skippers and

Uniqueness of the gauge invariant action for cosmological perturbations

International Nuclear Information System (INIS)

Prokopec, Tomislav; Weenink, Jan

2012-01-01

In second order perturbation theory different definitions are known of gauge invariant perturbations in single field inflationary models. Consequently the corresponding gauge invariant cubic actions do not have the same form. Here we show that the cubic action for one choice of gauge invariant variables is unique in the following sense: the action for any other, non-linearly related variable can be brought to the same bulk action, plus additional boundary terms. These boundary terms correspond to the choice of hypersurface and generate extra, disconnected contributions to the bispectrum. We also discuss uniqueness of the action with respect to conformal frames. When expressed in terms of the gauge invariant curvature perturbation on uniform field hypersurfaces the action for cosmological perturbations has a unique form, independent of the original Einstein or Jordan frame. Crucial is that the gauge invariant comoving curvature perturbation is frame independent, which makes it extremely helpful in showing the quantum equivalence of the two frames, and therefore in calculating quantum effects in nonminimally coupled theories such as Higgs inflation

Botulinum neurotoxin: unique folding of enzyme domain of the most-poisonous poison.

Science.gov (United States)

Kumar, Raj; Kukreja, Roshan V; Li, Li; Zhmurov, Artem; Kononova, Olga; Cai, Shuowei; Ahmed, Syed A; Barsegov, Valeri; Singh, Bal Ram

2014-01-01

Botulinum neurotoxin (BoNT), the most toxic substance known to mankind, is the first example of the fully active molten globule state. To understand its folding mechanism, we performed urea denaturation experiments and theoretical modeling using BoNT serotype A (BoNT/A). We found that the extent of BoNT/A denaturation from the native state (N) shows a nonmonotonic dependence on urea concentration indicating a unique multistep denaturation process, N → I1 [Formula: see text] I2 [Formula: see text] U, with two intermediate states I1 and I2. BoNT/A loses almost all its secondary structure in 3.75 M urea (I1), yet it displays a native-like secondary structure in 5 M urea (I2). This agrees with the results of theoretical modeling, which helped to determine the molecular basis of unique behavior of BoNT/A in solution. Except for I2, all the states revert back to full enzymatic activity for SNAP-25 including the unfolded state U stable in 7 M urea. Our results stress the importance of structural flexibility in the toxin's mechanism of survival and action, an unmatched evolutionary trait from billion-year-old bacteria, which also correlates with the long-lasting enzymatic activity of BoNT inside neuronal cells. BoNT/A provides a rich model to explore protein folding in relation to functional activity.

Uniqueness of Gibbs states and global Markov property for Euclidean fields

International Nuclear Information System (INIS)

Albeverio, S.; Hoeegh-Krohn, R.

1981-01-01

The authors briefly discuss the proof of the uniqueness of solutions of the DLR equations (uniqueness of Gibbs states) in the class of regular generalized random fields (in the sense of having second moments bounded by those of some Euclidean field), for the Euclidean fields with trigonometric interaction. (Auth.)

Cytotoxic protein from the mushroom Coprinus comatus possesses a unique mode for glycan binding and specificity

Science.gov (United States)

Zhang, Peilan; Yang, Guang; Xia, Changqing; Polston, Jane E.; Li, Gengnan; Li, Shiwu; Lin, Zhao; Yang, Li-jun; Bruner, Steven D.

2017-01-01

Glycans possess significant chemical diversity; glycan binding proteins (GBPs) recognize specific glycans to translate their structures to functions in various physiological and pathological processes. Therefore, the discovery and characterization of novel GBPs and characterization of glycan–GBP interactions are significant to provide potential targets for therapeutic intervention of many diseases. Here, we report the biochemical, functional, and structural characterization of a 130-amino-acid protein, Y3, from the mushroom Coprinus comatus. Biochemical studies of recombinant Y3 from a yeast expression system demonstrated the protein is a unique GBP. Additionally, we show that Y3 exhibits selective and potent cytotoxicity toward human T-cell leukemia Jurkat cells compared with a panel of cancer cell lines via inducing caspase-dependent apoptosis. Screening of a glycan array demonstrated GalNAcβ1–4(Fucα1–3)GlcNAc (LDNF) as a specific Y3-binding ligand. To provide a structural basis for function, the crystal structure was solved to a resolution of 1.2 Å, revealing a single-domain αβα-sandwich motif. Two monomers were dimerized to form a large 10-stranded, antiparallel β-sheet flanked by α-helices on each side, representing a unique oligomerization mode among GBPs. A large glycan binding pocket extends into the dimeric interface, and docking of LDNF identified key residues for glycan interactions. Disruption of residues predicted to be involved in LDNF/Y3 interactions resulted in the significant loss of binding to Jurkat T-cells and severely impaired their cytotoxicity. Collectively, these results demonstrate Y3 to be a GBP with selective cytotoxicity toward human T-cell leukemia cells and indicate its potential use in cancer diagnosis and treatment. PMID:28784797

Simulation study on exchange interaction and unique magnetization near ferromagnetic morphotropic phase boundary.

Science.gov (United States)

Wei, Songrui; Liao, Xiaoqi; Gao, Yipeng; Yang, Sen; Wang, Dong; Song, Xiaoping

2017-11-08

Extensive efforts have been made in searching enhanced functionalities near the so-called morphotropic phase boundaries (MPBs) in both ferroelectric and ferromagnetic materials. Due to the exchange anti-symmetry of the wave function of fermions, it is widely recognized that the exchange interaction plays a critical role in ferromagnetism. As a quantum effect, the exchange interaction is magnitudes larger than electric interaction, leading to a fundamental difference between ferroelectricity and ferromagnetism. In this paper, we establish an energetic model capturing the interplay among the anisotropy energy, magnetostatic energy and the exchange energy to investigate systematically the effects of the exchange energy on the behavior of the ferromagnetic MPB. For the first time, it is found that the exchange energy can narrow the width of MPB region in the composition temperature phase diagram for ferromagnetic MPB systems. As temperature increases, MPB region becomes wider because of the weakening of the exchange interaction. Our simulation results suggest that the exchange energy play a critical role on the unique behavior of ferromagnetic MPB, which is in contrast different from that of ferroelectric MPB.

Marketing the Uniqueness of Small Towns. Revised.

Science.gov (United States)

Dunn, Douglas; Hogg, David H.

The key to marketing a town is determining and promoting the town's "differential advantage" or uniqueness that would make people want to visit or live there. Exercises to help communities gain important insights into the town's competitive edge include a brainstorming session with knowledgeable community members, a visitor…

Dissection of Ire1 functions reveals stress response mechanisms uniquely evolved in Candida glabrata.

Directory of Open Access Journals (Sweden)

Taiga Miyazaki

2013-01-01

Full Text Available Proper protein folding in the endoplasmic reticulum (ER is vital in all eukaryotes. When misfolded proteins accumulate in the ER lumen, the transmembrane kinase/endoribonuclease Ire1 initiates splicing of HAC1 mRNA to generate the bZIP transcription factor Hac1, which subsequently activates its target genes to increase the protein-folding capacity of the ER. This cellular machinery, called the unfolded protein response (UPR, is believed to be an evolutionarily conserved mechanism in eukaryotes. In this study, we comprehensively characterized mutant phenotypes of IRE1 and other related genes in the human fungal pathogen Candida glabrata. Unexpectedly, Ire1 was required for the ER stress response independently of Hac1 in this fungus. C. glabrata Ire1 did not cleave mRNAs encoding Hac1 and other bZIP transcription factors identified in the C. glabrata genome. Microarray analysis revealed that the transcriptional response to ER stress is not mediated by Ire1, but instead is dependent largely on calcineurin signaling and partially on the Slt2 MAPK pathway. The loss of Ire1 alone did not confer increased antifungal susceptibility in C. glabrata contrary to UPR-defective mutants in other fungi. Taken together, our results suggest that the canonical Ire1-Hac1 UPR is not conserved in C. glabrata. It is known in metazoans that active Ire1 nonspecifically cleaves and degrades a subset of ER-localized mRNAs to reduce the ER load. Intriguingly, this cellular response could occur in an Ire1 nuclease-dependent fashion in C. glabrata. We also uncovered the attenuated virulence of the C. glabrata Δire1 mutant in a mouse model of disseminated candidiasis. This study has unveiled the unique evolution of ER stress response mechanisms in C. glabrata.

Efficient Serial and Parallel Algorithms for Selection of Unique Oligos in EST Databases.

Science.gov (United States)

Mata-Montero, Manrique; Shalaby, Nabil; Sheppard, Bradley

2013-01-01

Obtaining unique oligos from an EST database is a problem of great importance in bioinformatics, particularly in the discovery of new genes and the mapping of the human genome. Many algorithms have been developed to find unique oligos, many of which are much less time consuming than the traditional brute force approach. An algorithm was presented by Zheng et al. (2004) which finds the solution of the unique oligos search problem efficiently. We implement this algorithm as well as several new algorithms based on some theorems included in this paper. We demonstrate how, with these new algorithms, we can obtain unique oligos much faster than with previous ones. We parallelize these new algorithms to further improve the time of finding unique oligos. All algorithms are run on ESTs obtained from a Barley EST database.

A unique tripartite collision tumor of the esophagus

Science.gov (United States)

Schizas, Dimitrios; Michalinos, Adamantios; Alexandrou, Paraskevi; Moris, Demetrios; Baliou, Evangelia; Tsilimigras, Diamantis; Throupis, Theodore; Liakakos, Theodore

2017-01-01

Abstract Rationale: We report a unique case of a tripartite esophageal collision tumor consisting of three separate histologic types. Patients concerns: Therapeutic dilemmas on the proper treatment of those rare neoplasms remain unanswered considering both proper surgical therapy and adjuvant therapy. Diagnose: In this paper, we report a unique case of a patient with a tripartite esophageal collision tumor consisting of a small cell carcinoma, an adenocarcinoma of medium differentiation and a signet ring cell carcinoma. Diagnosis is difficult as clinical presentation of the patient was undistinguishable from other, commoner tumor types. Interventions: The patient's diagnostic and therapeutic course along with available data on the collisions tumor's biological behavior and treatment are briefly discussed. Outcomes: Esophagectomy is the best treatment options for these patients. Unique nature of this tumor demands aggresive oncologic treatment. Lessons: Collision tumors are rare neoplasms consisting of distinct cell populations developing in juxtaposition to one another without any areas of intermingling. Various cell types can be found. However, collision neoplasms of the esophagus combining adenomatous and neuroendocrine components are exceedingly rare, with only 5 cases described to date in the literature. Given their rarity, limited information is available on their tumorigenesis, biological behavior and clinical course. In general, these tumors are aggressive neoplasms and significantly affect patient treatment and prognosis. PMID:29245236

A unique gesture of sharing

International Nuclear Information System (INIS)

Mustafa, T.

1985-01-01

The Atoms for Peace program was a unique gesture of sharing on the part of the leading industrialized nation, and has very few parallels in modern history. The author says one of the major advantages of the program for developing nations was the much needed stimulation of their indigenous science and technology efforts and the awakening of their governments to the multifaceted benefits of atomic energy. The author discusses how the program benefited Pakistan in the production of electrical energy and in the application of nuclear techniques in the fields of agriculture and medicine, which help to alleviate hunger and combat disease

A unique metal-semiconductor interface and resultant electron transfer phenomenon

OpenAIRE

Taft, S. L.

2012-01-01

An unusual electron transfer phenomenon has been identified from an n-type semiconductor to Schottky metal particles, the result of a unique metal semiconductor interface that results when the metal particles are grown from the semiconductor substrate. The unique interface acts as a one-way (rectifying) open gateway and was first identified in reduced rutile polycrystalline titanium dioxide (an n-type semiconductor) to Group VIII (noble) metal particles. The interface significantly affects th...

Sleep, Internalizing Problems, and Social Withdrawal: Unique Associations in Clinic-Referred Youth With Elevated Sluggish Cognitive Tempo Symptoms.

Science.gov (United States)

Rondon, Ana T; Hilton, Dane C; Jarrett, Matthew A; Ollendick, Thomas H

2018-02-01

We compared clinic-referred youth with ADHD + sluggish cognitive tempo (SCT; n = 34), ADHD Only ( n = 108), and SCT Only ( n = 22) on demographics, co-occurring symptomatology, comorbid diagnoses, and social functioning. In total, 164 youth (age = 6-17 years, M = 9.97) and their parent(s) presented to an outpatient clinic for a psychoeducational assessment. Between-group analyses and regressions were used to examine study variables. SCT groups were older and exhibited more parent-reported internalizing problems, externalizing problems, sleep problems, and social withdrawal on the Child Behavior Checklist. No significant differences emerged between groups on the Teacher Report Form. Regression analyses involving multiple covariates revealed that SCT symptoms were uniquely related to social withdrawal but not general social problems. Based on parent report, SCT symptoms have a unique relationship with internalizing problems, sleep problems, and social withdrawal. Future research should explore correlates of SCT in youth using multiple informants.

Parental Expressivity and Parenting Styles in Chinese Families: Prospective and Unique Relations to Children's Psychological Adjustment.

Science.gov (United States)

Chen, Stephen H; Zhou, Qing; Eisenberg, Nancy; Valiente, Carlos; Wang, Yun

2011-01-01

OBJECTIVES: Parents from different cultures differ in how frequently they express emotions. However, the generalizability of the relations between parental expressivity and child adjustment in non-Western cultures has not been extensively studied. The goal of the present study was to investigate prospective relations between parental expressivity within the family (positive, negative dominant, and negative submissive expressivity) and Chinese children's psychological adjustment, above and beyond parenting styles. DESIGN: The study used two waves (3.8 years apart) of longitudinal data from a sample (n= 425) of children in Beijing (mean ages = 7.7 years at T1 and 11.6 years at T2). Parental expressivity and parenting styles were self-reported. To reduce the potential measurement overlap, items that tap parental expression of emotions toward the child were removed from the parenting style measure. Children's adjustment was measured with parents', teachers', and peers' or children's reports. RESULTS: Consistent with findings with European American samples, parental negative dominant expressivity uniquely and positively predicted Chinese children's externalizing problems controlling for prior externalizing problems, parenting styles, and family SES. Neither parental expressivity nor parenting styles uniquely predicted social competence. CONCLUSIONS: Despite previously reported cultural differences in the mean levels of parental expressivity, some of the socialization functions of parental expressivity found in Western countries can be generalized to Chinese families. Although parental expressivity and parenting styles are related constructs, their unique relations to child's adjustment suggest that they should be examined as distinct processes.

Genome-Wide Identification of Genes Probably Relevant to the Uniqueness of Tea Plant (Camellia sinensis and Its Cultivars

Directory of Open Access Journals (Sweden)

Yan Wei

2015-01-01

Full Text Available Tea (Camellia sinensis is a popular beverage all over the world and a number of studies have focused on the genetic uniqueness of tea and its cultivars. However, molecular mechanisms underlying these phenomena are largely undefined. In this report, based on expression data available from public databases, we performed a series of analyses to identify genes probably relevant to the uniqueness of C. sinensis and two of its cultivars (LJ43 and ZH2. Evolutionary analyses showed that the evolutionary rates of genes involved in the pathways were not significantly different among C. sinensis, C. oleifera, and C. azalea. Interestingly, a number of gene families, including genes involved in the pathways synthesizing iconic secondary metabolites of tea plant, were significantly upregulated, expressed in C. sinensis (LJ43 when compared to C. azalea, and this may partially explain its higher content of flavonoid, theanine, and caffeine. Further investigation showed that nonsynonymous mutations may partially contribute to the differences between the two cultivars of C. sinensis, such as the chlorina and higher contents of amino acids in ZH2. Genes identified as candidates are probably relevant to the uniqueness of C. sinensis and its cultivars should be good candidates for subsequent functional analyses and marker-assisted breeding.

Cellular endocytic compartment localization of expressed canine CD1 molecules

DEFF Research Database (Denmark)

Schjærff, Mette; Keller, Stefan M.; Affolter, Verena K.

2016-01-01

CD1 molecules are glycoproteins present primarily on dendritic cells (DCs), which recognize and presenta variety of foreign- and self-lipid antigens to T-cells. Humans have five different CD1 isoforms that sur-vey distinct cellular compartments allowing for recognition of a large repertoire...... onlya diminished GFP expression. In conclusion, canine CD1 transfectants show distinct localization patternsthat are similar to human CD1 proteins with the exception of the canine CD1d isoform, which most likelyis non-functional. These findings imply that canine CD1 localization overall resembles human...... CD1 traf-ficking patterns. This knowledge is important for the understanding of lipid antigen-receptor immunityin the dog....

Common Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Epitopes Mediate Multiple Routes for Internalization and Function

Science.gov (United States)

DeVay, Rachel M.; Yamamoto, Lynn; Shelton, David L.; Liang, Hong

2015-01-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a soluble protein that directs membrane-bound receptors to lysosomes for degradation. In the most studied example of this, PCSK9 binding leads to the degradation of low density lipoprotein receptor (LDLR), significantly affecting circulating LDL-C levels. The mechanism mediating this degradation, however, is not completely understood. We show here that LDLR facilitates PCSK9 interactions with amyloid precursor like protein 2 (APLP2) at neutral pH leading to PCSK9 internalization, although direct binding between PCSK9 and LDLR is not required. Moreover, binding to APLP2 or LDLR is independently sufficient for PCSK9 endocytosis in hepatocytes, while LDL can compete with APLP2 for PCSK9 binding to indirectly mediate PCSK9 endocytosis. Finally, we show that APLP2 and LDLR are also required for the degradation of another PCSK9 target, APOER2, necessitating a general role for LDLR and APLP2 in PCSK9 function. Together, these findings provide evidence that PCSK9 has at least two endocytic epitopes that are utilized by a variety of internalization mechanisms and clarifies how PCSK9 may direct proteins to lysosomes. PMID:25905719

The Green functions in curved spacetime

International Nuclear Information System (INIS)

Buchbinder, I.L.; Kirillova, E.N.; Odinstov, S.D.

1987-01-01

The theory of a free scalar field with conformal coupling in curved spacetime with some special metrics is considered. The integral representations for the green function G-tilde in the form of integrals with Schwinger-De Witt kernel over contours in the complex plane of proper time are obtained. It is shown how the transitions from a unique Green function in Euclidean space to different Green functions in Minkowski space and vice versa can be carried out. (author)

The unique stem cell system of the immortal larva of the human parasite Echinococcus multilocularis

Science.gov (United States)

2014-01-01

Background It is believed that in tapeworms a separate population of undifferentiated cells, the germinative cells, is the only source of cell proliferation throughout the life cycle (similar to the neoblasts of free living flatworms). In Echinococcus multilocularis, the metacestode larval stage has a unique development, growing continuously like a mass of vesicles that infiltrate the tissues of the intermediate host, generating multiple protoscoleces by asexual budding. This unique proliferation potential indicates the existence of stem cells that are totipotent and have the ability for extensive self-renewal. Results We show that only the germinative cells proliferate in the larval vesicles and in primary cell cultures that undergo complete vesicle regeneration, by using a combination of morphological criteria and by developing molecular markers of differentiated cell types. The germinative cells are homogeneous in morphology but heterogeneous at the molecular level, since only sub-populations express homologs of the post-transcriptional regulators nanos and argonaute. Important differences are observed between the expression patterns of selected neoblast marker genes of other flatworms and the E. multilocularis germinative cells, including widespread expression in E. multilocularis of some genes that are neoblast-specific in planarians. Hydroxyurea treatment results in the depletion of germinative cells in larval vesicles, and after recovery following hydroxyurea treatment, surviving proliferating cells grow as patches that suggest extensive self-renewal potential for individual germinative cells. Conclusions In E. multilocularis metacestodes, the germinative cells are the only proliferating cells, presumably driving the continuous growth of the larval vesicles. However, the existence of sub-populations of the germinative cells is strongly supported by our data. Although the germinative cells are very similar to the neoblasts of other flatworms in function and

A unique theory of all forces

International Nuclear Information System (INIS)

Di Vecchia, Paolo

1997-01-01

In discussing the construction of a consistent theory of quantum gravity unified with the gauge interactions we are naturally led to a string theory. We review its properties and the five consistent supersymmetric string theories in ten dimensions. We finally discuss the evidence that these theories are actually special limits of a unique 11-dimensional theory, called M-theory, and a recent conjecture for its explicit formulation as a supersymmetric Matrix theory

EEG Oscillatory States: Universality, Uniqueness and Specificity across Healthy-Normal, Altered and Pathological Brain Conditions

Science.gov (United States)

Fingelkurts, Alexander A.; Fingelkurts, Andrew A.

2014-01-01

For the first time the dynamic repertoires and oscillatory types of local EEG states in 13 diverse conditions (examined over 9 studies) that covered healthy-normal, altered and pathological brain states were quantified within the same methodological and conceptual framework. EEG oscillatory states were assessed by the probability-classification analysis of short-term EEG spectral patterns. The results demonstrated that brain activity consists of a limited repertoire of local EEG states in any of the examined conditions. The size of the state repertoires was associated with changes in cognition and vigilance or neuropsychopathologic conditions. Additionally universal, optional and unique EEG states across 13 diverse conditions were observed. It was demonstrated also that EEG oscillations which constituted EEG states were characteristic for different groups of conditions in accordance to oscillations’ functional significance. The results suggested that (a) there is a limit in the number of local states available to the cortex and many ways in which these local states can rearrange themselves and still produce the same global state and (b) EEG individuality is determined by varying proportions of universal, optional and unique oscillatory states. The results enriched our understanding about dynamic microstructure of EEG-signal. PMID:24505292

Unique physiology of host-parasite interactions in microsporidia infections.

Science.gov (United States)

Williams, Bryony A P

2009-11-01

Microsporidia are intracellular parasites of all major animal lineages and have a described diversity of over 1200 species and an actual diversity that is estimated to be much higher. They are important pathogens of mammals, and are now one of the most common infections among immunocompromised humans. Although related to fungi, microsporidia are atypical in genomic biology, cell structure and infection mechanism. Host cell infection involves the rapid expulsion of a polar tube from a dormant spore to pierce the host cell membrane and allow the direct transfer of the spore contents into the host cell cytoplasm. This intimate relationship between parasite and host is unique. It allows the microsporidia to be highly exploitative of the host cell environment and cause such diverse effects as the induction of hypertrophied cells to harbour prolific spore development, host sex ratio distortion and host cell organelle and microtubule reorganization. Genome sequencing has revealed that microsporidia have achieved this high level of parasite sophistication with radically reduced proteomes and with many typical eukaryotic pathways pared-down to what appear to be minimal functional units. These traits make microsporidia intriguing model systems for understanding the extremes of reductive parasite evolution and host cell manipulation.

Synthesis and Characterization of Block Copolymers with Unique Chemical Functionalities and Entropically-Hindering Moieties

Science.gov (United States)

2017-08-14

methanol as a function of chemistry , morphology and hydration levels. Accomplishments: This section is included in the "upload" section. Training...Copolymer Blend Membranes.” In Press, Polymer Engineering and Science, DOI: 10.1002 /pen.24508, 2017. 5. M. Pérez-Pérez and D. Suleiman. “Synthesis and...Synthesis and Characterization of Sulfonated Amine Block Copolymers for Energy Efficient Applications". Chemical Engineering Symposium, University of

Is Self-Assessment in Religious Education Unique?

Science.gov (United States)

Brooks, Val; Fancourt, Nigel

2012-01-01

This paper addresses the question: is self-assessment in religious education unique? It first presents an overview of some challenges for assessment from subject differences, and then reviews the generic literature on self-assessment. It builds on earlier empirical research on self-assessment in religious education, carried out in an English state…

A unique bivalent binding and inhibition mechanism by the yatapoxvirus interleukin 18 binding protein.

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Brian Krumm

Full Text Available Interleukin 18 (IL18 is a cytokine that plays an important role in inflammation as well as host defense against microbes. Mammals encode a soluble inhibitor of IL18 termed IL18 binding protein (IL18BP that modulates IL18 activity through a negative feedback mechanism. Many poxviruses encode homologous IL18BPs, which contribute to virulence. Previous structural and functional studies on IL18 and IL18BPs revealed an essential binding hot spot involving a lysine on IL18 and two aromatic residues on IL18BPs. The aromatic residues are conserved among the very diverse mammalian and poxviruses IL18BPs with the notable exception of yatapoxvirus IL18BPs, which lack a critical phenylalanine residue. To understand the mechanism by which yatapoxvirus IL18BPs neutralize IL18, we solved the crystal structure of the Yaba-Like Disease Virus (YLDV IL18BP and IL18 complex at 1.75 Å resolution. YLDV-IL18BP forms a disulfide bonded homo-dimer engaging IL18 in a 2∶2 stoichiometry, in contrast to the 1∶1 complex of ectromelia virus (ECTV IL18BP and IL18. Disruption of the dimer interface resulted in a functional monomer, however with a 3-fold decrease in binding affinity. The overall architecture of the YLDV-IL18BP:IL18 complex is similar to that observed in the ECTV-IL18BP:IL18 complex, despite lacking the critical lysine-phenylalanine interaction. Through structural and mutagenesis studies, contact residues that are unique to the YLDV-IL18BP:IL18 binding interface were identified, including Q67, P116 of YLDV-IL18BP and Y1, S105 and D110 of IL18. Overall, our studies show that YLDV-IL18BP is unique among the diverse family of mammalian and poxvirus IL-18BPs in that it uses a bivalent binding mode and a unique set of interacting residues for binding IL18. However, despite this extensive divergence, YLDV-IL18BP binds to the same surface of IL18 used by other IL18BPs, suggesting that all IL18BPs use a conserved inhibitory mechanism by blocking a putative receptor

Why are predictions of general relativity theory for gravitational effects non-unique?

International Nuclear Information System (INIS)

Loskutov, Yu.M.

1990-01-01

Reasons of non-uniqueness of predictions of the general relativity theory (GRT) for gravitational effects are analyzed in detail. To authors' opinion, the absence of comparison mechanism of curved and plane metrics is the reason of non-uniqueness

A unique dual activity amino acid hydroxylase in Toxoplasma gondii.

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Elizabeth A Gaskell

Full Text Available The genome of the protozoan parasite Toxoplasma gondii was found to contain two genes encoding tyrosine hydroxylase; that produces L-DOPA. The encoded enzymes metabolize phenylalanine as well as tyrosine with substrate preference for tyrosine. Thus the enzymes catabolize phenylalanine to tyrosine and tyrosine to L-DOPA. The catalytic domain descriptive of this class of enzymes is conserved with the parasite enzyme and exhibits similar kinetic properties to metazoan tyrosine hydroxylases, but contains a unique N-terminal extension with a signal sequence motif. One of the genes, TgAaaH1, is constitutively expressed while the other gene, TgAaaH2, is induced during formation of the bradyzoites of the cyst stages of the life cycle. This is the first description of an aromatic amino acid hydroxylase in an apicomplexan parasite. Extensive searching of apicomplexan genome sequences revealed an ortholog in Neospora caninum but not in Eimeria, Cryptosporidium, Theileria, or Plasmodium. Possible role(s of these bi-functional enzymes during host infection are discussed.

Progranulin Is a Chemoattractant for Microglia and Stimulates Their Endocytic Activity

OpenAIRE

Pickford, Fiona; Marcus, Jacob; Camargo, Luiz Miguel; Xiao, Qiurong; Graham, Danielle; Mo, Jan-Rung; Burkhardt, Matthew; Kulkarni, Vinayak; Crispino, Jamie; Hering, Heike; Hutton, Michael

2011-01-01

Mutations resulting in progranulin haploinsufficiency cause disease in patients with a subset of frontotemporal lobar degeneration; however, the biological functions of progranulin in the brain remain unknown. To address this subject, the present study initially assessed changes in gene expression and cytokine secretion in rat primary cortical neurons treated with progranulin. Molecular pathways enriched in the progranulin gene set included cell adhesion and cell motility pathways and pathway...

Uniqueness of flat spherically symmetric spacelike hypersurfaces admitted by spherically symmetric static spacetimes

Science.gov (United States)

Beig, Robert; Siddiqui, Azad A.

2007-11-01

It is known that spherically symmetric static spacetimes admit a foliation by flat hypersurfaces. Such foliations have explicitly been constructed for some spacetimes, using different approaches, but none of them have proved or even discussed the uniqueness of these foliations. The issue of uniqueness becomes more important due to suitability of flat foliations for studying black hole physics. Here, flat spherically symmetric spacelike hypersurfaces are obtained by a direct method. It is found that spherically symmetric static spacetimes admit flat spherically symmetric hypersurfaces, and that these hypersurfaces are unique up to translation under the timelike Killing vector. This result guarantees the uniqueness of flat spherically symmetric foliations for such spacetimes.

Young children's preference for unique owned objects.

Science.gov (United States)

Gelman, Susan A; Davidson, Natalie S

2016-10-01

An important aspect of human thought is the value we place on unique individuals. Adults place higher value on authentic works of art than exact replicas, and young children at times value their original possessions over exact duplicates. What is the scope of this preference in early childhood, and when do children understand its subjective nature? On a series of trials, we asked three-year-olds (N=36) to choose between two toys for either themselves or the researcher: an old (visibly used) toy vs. a new (more attractive) toy matched in type and appearance (e.g., old vs. brand-new blanket). Focal pairs contrasted the child's own toy with a matched new object; Control pairs contrasted toys the child had never seen before. Children preferred the old toys for Focal pairs only, and treated their own preferences as not shared by the researcher. By 3years of age, young children place special value on unique individuals, and understand the subjective nature of that value. Copyright © 2016 Elsevier B.V. All rights reserved.

Event segmentation ability uniquely predicts event memory.

Science.gov (United States)

Sargent, Jesse Q; Zacks, Jeffrey M; Hambrick, David Z; Zacks, Rose T; Kurby, Christopher A; Bailey, Heather R; Eisenberg, Michelle L; Beck, Taylor M

2013-11-01

Memory for everyday events plays a central role in tasks of daily living, autobiographical memory, and planning. Event memory depends in part on segmenting ongoing activity into meaningful units. This study examined the relationship between event segmentation and memory in a lifespan sample to answer the following question: Is the ability to segment activity into meaningful events a unique predictor of subsequent memory, or is the relationship between event perception and memory accounted for by general cognitive abilities? Two hundred and eight adults ranging from 20 to 79years old segmented movies of everyday events and attempted to remember the events afterwards. They also completed psychometric ability tests and tests measuring script knowledge for everyday events. Event segmentation and script knowledge both explained unique variance in event memory above and beyond the psychometric measures, and did so as strongly in older as in younger adults. These results suggest that event segmentation is a basic cognitive mechanism, important for memory across the lifespan. Copyright © 2013 Elsevier B.V. All rights reserved.

Visuomotor Integration and Executive Functioning Are Uniquely Linked to Chinese Word Reading and Writing in Kindergarten Children

Science.gov (United States)

Chung, Kevin Kien Hoa; Lam, Chun Bun; Cheung, Ka Chun

2018-01-01

This cross-sectional study examined the associations of visuomotor integration and executive functioning with Chinese word reading and writing in kindergarten children. A total of 369 Chinese children (mean age = 57.99 months; 55% of them were girls) from Hong Kong, China, completed tasks on visuomotor integration, executive functioning, and…

Modularity, comparative cognition and human uniqueness

OpenAIRE

Shettleworth, Sara J.

2012-01-01

Darwin's claim ‘that the difference in mind between man and the higher animals … is certainly one of degree and not of kind’ is at the core of the comparative study of cognition. Recent research provides unprecedented support for Darwin's claim as well as new reasons to question it, stimulating new theories of human cognitive uniqueness. This article compares and evaluates approaches to such theories. Some prominent theories propose sweeping domain-general characterizations of the difference ...

Increasing Need for Uniqueness in Contemporary China: Empirical Evidence

Directory of Open Access Journals (Sweden)

Huajian Cai

2018-05-01

Full Text Available Past research has documented various cultural and psychological changes in contemporary China. In two studies, we examine how Chinese people’s need for uniqueness (NFU also has changed. In Study 1, we found a significant cross-generational increase in Chinese participants’ self-reported NFU. In Study 2, we sampled the names of Chinese newborn babies over the last five decades and found that parents have been increasingly likely to use unique characters to name their children. These findings suggest that the NFU has been rising in China, a historically collectivistic-oriented society. Theoretical and practical implications of our findings were discussed.

A Meta-model for the Assessment of Non-Functional Requirement Size

NARCIS (Netherlands)

Kassab, M.; Daneva, Maia; Ormandjieva, O.; Mirandola, R.

2008-01-01

Non-functional requirements (NFRs) pose unique challenges in estimating the effort it would take to implement them. This is mainly because of their unique nature; NFRs are subjective, relative, interactive and tending to have a broad impact on the system as a whole. Nevertheless, it is crucial, when

Bent functions results and applications to cryptography

CERN Document Server

Tokareva, Natalia

2015-01-01

Bent Functions: Results and Applications to Cryptography offers a unique survey of the objects of discrete mathematics known as Boolean bent functions. As these maximal, nonlinear Boolean functions and their generalizations have many theoretical and practical applications in combinatorics, coding theory, and cryptography, the text provides a detailed survey of their main results, presenting a systematic overview of their generalizations and applications, and considering open problems in classification and systematization of bent functions. The text is appropriate for novices and advanced

A note on unique solvability of the absolute value equation

Directory of Open Access Journals (Sweden)

Taher Lotfi

2014-05-01

Full Text Available It is proved that applying sufficient regularity conditions to the interval matrix $[A-|B|,A+|B|]$‎, ‎we can create a new unique solvability condition for the absolute value equation $Ax+B|x|=b$‎, ‎since regularity of interval matrices implies unique solvability of their corresponding absolute value equation‎. ‎This condition is formulated in terms of positive definiteness of a certain point matrix‎. ‎Special case $B=-I$ is verified too as an application.

Unique and shared areas of cognitive function in children with intractable frontal or temporal lobe epilepsy.

Science.gov (United States)

Law, Nicole; Widjaja, Elysa; Smith, Mary Lou

2018-03-01

Previous findings have been mixed in terms of identifying a distinct pattern of neuropsychological deficits in children with frontal lobe epilepsy (FLE) and in those with temporal lobe epilepsy (TLE). The current study investigated the neuropsychological similarities and differences across these two pediatric medically intractable localization-related epilepsies. Thirty-eight children with FLE, 20 children with TLE, and 40 healthy children (HC) participated in this study. A comprehensive battery of standardized tests assessed five neuropsychological domains including intelligence, language, memory, executive function, and motor function. A principal component analysis (PCA) was used to distill our neuropsychological measures into latent components to compare between groups. Principal component analysis extracted 5 latent components: executive function (F1), verbal semantics (F2), motor (F3), nonverbal cognition/impulsivity (F4), and verbal cognition/attention (F5). The group with FLE differed from the HC group on F1, F2, F4, and F5, and had worse performance than the group with TLE on F1; the group with TLE had lower performance relative to the HC group on F2. Our findings suggest that, in comparison with neurotypically developing children, children with medically intractable FLE have more widespread neuropsychological impairments than do children with TLE. The differences between the two patient groups were greatest for the factor score most clearly related to executive function. The results provide mixed support for the concept of specificity in neuropsychological dysfunction among different subtypes of localization-related medically intractable childhood epilepsies. Copyright © 2018 Elsevier Inc. All rights reserved.

Uniqueness: skews bit occurrence frequencies in randomly generated fingerprint libraries.

Science.gov (United States)

Chen, Nelson G

2016-08-01

Requiring that randomly generated chemical fingerprint libraries have unique fingerprints such that no two fingerprints are identical causes a systematic skew in bit occurrence frequencies, the proportion at which specified bits are set. Observed frequencies (O) at which each bit is set within the resulting libraries systematically differ from frequencies at which bits are set at fingerprint generation (E). Observed frequencies systematically skew toward 0.5, with the effect being more pronounced as library size approaches the compound space, which is the total number of unique possible fingerprints given the number of bit positions each fingerprint contains. The effect is quantified for varying library sizes as a fraction of the overall compound space, and for changes in the specified frequency E. The cause and implications for this systematic skew are subsequently discussed. When generating random libraries of chemical fingerprints, the imposition of a uniqueness requirement should either be avoided or taken into account.

RUCS: Rapid identification of PCR primers for unique core sequences

DEFF Research Database (Denmark)

Thomsen, Martin Christen Frølund; Hasman, Henrik; Westh, Henrik

2017-01-01

Designing PCR primers to target a specific selection of whole genome sequenced strains can be a long, arduous, and sometimes impractical task. Such tasks would benefit greatly from an automated tool to both identify unique targets, and to validate the vast number of potential primer pairs...... for the targets in silico . Here we present RUCS, a program that will find PCR primer pairs and probes for the unique core sequences of a positive genome dataset complement to a negative genome dataset. The resulting primer pairs and probes are in addition to simple selection also validated through a complex...... in silico PCR simulation. We compared our method, which identifies the unique core sequences, against an existing tool called ssGeneFinder, and found that our method was 6.5-20 times more sensitive. We used RUCS to design primer pairs that would target a set of genomes known to contain the mcr-1 colistin...

Toward discovery science of human brain function

DEFF Research Database (Denmark)

Biswal, Bharat B; Mennes, Maarten; Zuo, Xi-Nian

2010-01-01

Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints...... individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships...... in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/....

A Content Analysis of Unique Selling Propositions of Tobacco Print Ads.

Science.gov (United States)

Johnson Shen, Megan; Banerjee, Smita C; Greene, Kathryn; Carpenter, Amanda; Ostroff, Jamie S

2017-03-01

We describe the unique selling propositions (USPs) (propositions used to convince customers to use a particular brand/product by focusing on the unique benefit) of print tobacco ads. A qualitative content analysis was conducted of print tobacco ads (N = 171) selected from August 2012 to August 2013 for cigarettes, moist snuff, e-cigarettes, cigars, and snus to determine the content and themes of USPs for tobacco ads. Cigarette ad USP themes focused on portraying the product as attractive; moist snuff ads focused on portraying product as masculine; cigar ads focused on selling a "high end product;" and new and emerging tobacco products (e-cigarette, snus) focused on directly comparing these products to cigarettes. Whereas traditional tobacco product ads used USPs focused on themes of enjoyment and pleasure (eg, attractive for cigarettes, "high end product" for cigars), new and emerging tobacco product ads offered the unique benefit (USP) of their product being a better and "safer" alternative to traditional tobacco products. Snuff's USPs focused nearly exclusively on the masculinity of their products. Our results provide targets for potential tobacco regulatory actions that could be implemented to reduce demand for tobacco products by reducing their perceived unique benefits.

Uniqueness and Asymptotic Behavior of Positive Solutions for a Fractional-Order Integral Boundary Value Problem

Directory of Open Access Journals (Sweden)

Min Jia

2012-01-01

Full Text Available We study a model arising from porous media, electromagnetic, and signal processing of wireless communication system -tαx(t=f(t,x(t,x'(t,x”(t,…,x(n-2(t,  0functionals given by Riemann-Stieltjes integrals, A is a function of bounded variation, and dA can be a changing-sign measure. The existence, uniqueness, and asymptotic behavior of positive solutions to the singular nonlocal integral boundary value problem for fractional differential equation are obtained. Our analysis relies on Schauder's fixed-point theorem and upper and lower solution method.

Qualitative properties of functional differential equation

Directory of Open Access Journals (Sweden)

Diana Otrocol

2014-10-01

Full Text Available The aim of this paper is to discuss some basic problems (existence and uniqueness, data dependence of the fixed point theory for a functional differential equation with an abstract Volterra operator. In the end an application is given.

Alcohol and cannabinoids differentially affect HIV infection and function of human monocyte-derived dendritic cells (MDDC

Directory of Open Access Journals (Sweden)

Marisela eAgudelo

2015-12-01

Full Text Available During human immunodeficiency virus (HIV infection, alcohol has been known to induce inflammation while cannabinoids have been shown to have an anti-inflammatory role. For instance cannabinoids have been shown to reduce susceptibility to HIV-1 infection and attenuate HIV replication in macrophages. Recently, we demonstrated that alcohol induces cannabinoid receptors and regulates cytokine production by monocyte-derived dendritic cells (MDDC. However, the ability of alcohol and cannabinoids to alter MDDC function during HIV infection has not been clearly elucidated yet. In order to study the potential impact of alcohol and cannabinoids on differentiated MDDC infected with HIV, monocytes were cultured for 7 days with GM-CSF and IL-4, differentiated MDDC were infected with HIV-1Ba-L and treated with EtOH (0.1 and 0.2%, THC (5 and 10 uM, or JWH-015 (5 and 10 uM for 4-7 days. HIV infection of MDDC was confirmed by p24 and Long Terminal Repeats (LTR estimation. MDDC endocytosis assay and cytokine array profiles were measured to investigate the effects of HIV and substances of abuse on MDDC function. Our results show the HIV+EtOH treated MDDC had the highest levels of p24 production and expression when compared with the HIV positive controls and the cannabinoid treated cells. Although both cannabinoids, THC and JWH-015 had lower levels of p24 production and expression, the HIV+JWH-015 treated MDDC had the lowest levels of p24 when compared to the HIV+THC treated cells. In addition, MDDC endocytic function and cytokine production were also differentially altered after alcohol and cannabinoid treatments. Our results show a differential effect of alcohol and cannabinoids, which may provide insights into the divergent inflammatory role of alcohol and cannabinoids to modulate MDDC function in the context of HIV infection.

Edges and vertices in a unique signed circle in a signed graph

Directory of Open Access Journals (Sweden)

Richard Behr

2017-12-01

Full Text Available We examine the conditions under which a signed graph contains an edge or a vertex that is contained in a unique negative circle or a unique positive circle. For an edge in a unique signed circle, the positive and negative case require the same structure on the underlying graph, but the requirements on the signature are different. We characterize the structure of the underlying graph necessary to support such an edge in terms of bridges of a circle. We then use the results from the edge version of the problem to help solve the vertex version.

Being and feeling unique: statistical deviance and psychological marginality.

Science.gov (United States)

Frable, D E

1993-03-01

Two studies tested the hypothesis that people with culturally stigmatized and concealable conditions (e.g., gays, epileptics, juvenile delinquents, and incest victims) would be more likely to feel unique than people with culturally valued or conspicuous conditions (e.g., the physically attractive, the intellectually gifted, the obese, and the facially scarred). In Study 1, culturally stigmatized individuals with concealable conditions were least likely to perceive consensus between their personal preferences and those of others. In Study 2, they were most likely to describe themselves as unique and to make these self-relevant decisions quickly. Marginality is a psychological reality, not just a statistical one, for those with stigmatized and concealable "master status" conditions.

On the Existence and Uniqueness of the Scientific Method.

Science.gov (United States)

Wagensberg, Jorge

2014-01-01

The ultimate utility of science is widely agreed upon: the comprehension of reality. But there is much controversy about what scientific understanding actually means, and how we should proceed in order to gain new scientific understanding. Is there a method for acquiring new scientific knowledge? Is this method unique and universal? There has been no shortage of proposals, but neither has there been a shortage of skeptics about these proposals. This article proffers for discussion a potential scientific method that aspires to be unique and universal and is rooted in the recent and ancient history of scientific thinking. Curiously, conclusions can be inferred from this scientific method that also concern education and the transmission of science to others.

Uniqueness of KMS states for continuous fermion systems

International Nuclear Information System (INIS)

Jaekel, C.D.

1993-01-01

In 1989 Prof H. Narnhofer and Prof. W. Thirring established a (nonlocal) model of fermions with pair interactions. The existence of equilibrium states and the appearance of mixing properties was proofed. If this model reflects the basic facts of nature, one has to expect and to require that at high temperatures there is a unique equilibrium state and at low temperatures there are many different equilibrium states. Uniqueness of the equilibrium state at high temperatures is the topic of this dissertation. One may be astonished, that the proof of the uniqueness requires such a huge machinery, while the existence of KMS-states followes from fairly general conditions. Two states differ, if they can be distinguished by experiment. If one considers now that we have to show that two KMS-states at high temperatures result into the same value in all experiments one can think of, one might get an idea how unhandy this problem is. Even a conscious numeration of all experiments was a problem. Surprisingly only a few principal ideas of the treatment of spin-models survive. The temperature is the leading parameter and therefore it is a good idea to make a high temperature perturbation expansion for the KMS-condition, which fixes an equilibrium state in mathematical terms. But when we choose a generating vector for the perturbation expansion the similarities end. We better use physical considerations: at high temperatures we expect that chemical bounds will be broken up and the interacting equilibrium state will differ only slightly from the equilibrium state for the free time evolution. Roughly spoken, one can expect that high-energetic particles neglect interactions and fly in a straight line. In chapter 2.4 the whole machinery is presented in an easy-to-survey manner on a simple interaction. But in the case of pair interactions every particle interacts with each other and so the author was not able to find an easily accessible form of the developed method for this case

Oxidative stress induces caveolin 1 degradation and impairs caveolae functions in skeletal muscle cells.

Directory of Open Access Journals (Sweden)

Alexis Mougeolle

Full Text Available Increased level of oxidative stress, a major actor of cellular aging, impairs the regenerative capacity of skeletal muscle and leads to the reduction in the number and size of muscle fibers causing sarcopenia. Caveolin 1 is the major component of caveolae, small membrane invaginations involved in signaling and endocytic trafficking. Their role has recently expanded to mechanosensing and to the regulation of oxidative stress-induced pathways. Here, we increased the amount of reactive oxidative species in myoblasts by addition of hydrogen peroxide (H2O2 at non-toxic concentrations. The expression level of caveolin 1 was significantly decreased as early as 10 min after 500 μM H2O2 treatment. This reduction was not observed in the presence of a proteasome inhibitor, suggesting that caveolin 1 was rapidly degraded by the proteasome. In spite of caveolin 1 decrease, caveolae were still able to assemble at the plasma membrane. Their functions however were significantly perturbed by oxidative stress. Endocytosis of a ceramide analog monitored by flow cytometry was significantly diminished after H2O2 treatment, indicating that oxidative stress impaired its selective internalization via caveolae. The contribution of caveolae to the plasma membrane reservoir has been monitored after osmotic cell swelling. H2O2 treatment increased membrane fragility revealing that treated cells were more sensitive to an acute mechanical stress. Altogether, our results indicate that H2O2 decreased caveolin 1 expression and impaired caveolae functions. These data give new insights on age-related deficiencies in skeletal muscle.

The Relations of Family Members’ Unique and Shared Perspectives of Family Dysfunction to Dyad Adjustment

Science.gov (United States)

Jager, Justin; Yuen, Cynthia X.; Bornstein, Marc H.; Putnick, Diane L.; Hendricks, Charlene

2017-01-01

Among a community sample of families (N = 128), this study examined how family members’ shared and unique perspectives of family dysfunction relate to dyad members’ shared views of dyad adjustment within adolescent-mother, adolescent-father, and mother-father dyads. Independent of a family’s family perspective (shared perspective of family dysfunction), the adolescent’s unique perspective was associated with lower security and higher conflict with both mother and father, the father’s unique perspective was associated with lower security and higher conflict with the adolescent as well as lower marital quality with mother, and the mother unique perspective was associated with lower marital quality with the father. Moreover, for adolescent-parent dyads, compared to the parent unique perspective, the adolescent unique perspective was more strongly associated with dyad adjustment. These findings indicate that both shared and unique views of the family system – the adolescent’s unique view in particular - independently relate to the health of family subsystems. They also suggest that research as well as therapeutic interventions that focus on just the shared view of the family may miss important elements of family dysfunction. PMID:24884682

Distinct Domains of CheA Confer Unique Functions in Chemotaxis and Cell Length in Azospirillum brasilense Sp7.

Science.gov (United States)

Gullett, Jessica M; Bible, Amber; Alexandre, Gladys

2017-07-01

Chemotaxis is the movement of cells in response to gradients of diverse chemical cues. Motile bacteria utilize a conserved chemotaxis signal transduction system to bias their motility and navigate through a gradient. A central regulator of chemotaxis is the histidine kinase CheA. This cytoplasmic protein interacts with membrane-bound receptors, which assemble into large polar arrays, to propagate the signal. In the alphaproteobacterium Azospirillum brasilense , Che1 controls transient increases in swimming speed during chemotaxis, but it also biases the cell length at division. However, the exact underlying molecular mechanisms for Che1-dependent control of multiple cellular behaviors are not known. Here, we identify specific domains of the CheA1 histidine kinase implicated in modulating each of these functions. We show that CheA1 is produced in two isoforms: a membrane-anchored isoform produced as a fusion with a conserved seven-transmembrane domain of unknown function (TMX) at the N terminus and a soluble isoform similar to prototypical CheA. Site-directed and deletion mutagenesis combined with behavioral assays confirm the role of CheA1 in chemotaxis and implicate the TMX domain in mediating changes in cell length. Fluorescence microscopy further reveals that the membrane-anchored isoform is distributed around the cell surface while the soluble isoform localizes at the cell poles. Together, the data provide a mechanism for the role of Che1 in controlling multiple unrelated cellular behaviors via acquisition of a new domain in CheA1 and production of distinct functional isoforms. IMPORTANCE Chemotaxis provides a significant competitive advantage to bacteria in the environment, and this function has been transferred laterally multiple times, with evidence of functional divergence in different genomic contexts. The molecular principles that underlie functional diversification of chemotaxis in various genomic contexts are unknown. Here, we provide a molecular

Marginal and happy? The need for uniqueness predicts the adjustment of marginal immigrants.

Science.gov (United States)

Debrosse, Régine; de la Sablonnière, Roxane; Rossignac-Milon, Maya

2015-12-01

Marginalization is often presented as the strategy associated with the worst adjustment for immigrants. This study identifies a critical variable that buffers marginal immigrants from the negative effects of marginalization on adjustment: The need for uniqueness. In three studies, we surveyed immigrants recruited on university campuses (n = 119, n = 116) and in the field (n = 61). Among marginal immigrants, a higher need for uniqueness predicted higher self-esteem (Study 1), affect (Study 2), and life satisfaction (Study 3), and marginally higher happiness (Study 2) and self-esteem (Study 3). No relationship between the need for uniqueness and adjustment was found among non-marginal immigrants. The adaptive value of the need for uniqueness for marginal immigrants is discussed. © 2015 The British Psychological Society.

The neXtProt peptide uniqueness checker: a tool for the proteomics community.

Science.gov (United States)

Schaeffer, Mathieu; Gateau, Alain; Teixeira, Daniel; Michel, Pierre-André; Zahn-Zabal, Monique; Lane, Lydie

2017-11-01

The neXtProt peptide uniqueness checker allows scientists to define which peptides can be used to validate the existence of human proteins, i.e. map uniquely versus multiply to human protein sequences taking into account isobaric substitutions, alternative splicing and single amino acid variants. The pepx program is available at https://github.com/calipho-sib/pepx and can be launched from the command line or through a cgi web interface. Indexing requires a sequence file in FASTA format. The peptide uniqueness checker tool is freely available on the web at https://www.nextprot.org/tools/peptide-uniqueness-checker and from the neXtProt API at https://api.nextprot.org/. lydie.lane@sib.swiss. © The Author(s) 2017. Published by Oxford University Press.

Analytic perturbation theory for screened Coulomb potential: full continuum wave function

International Nuclear Information System (INIS)

Bechler, A.; Ennan, Mc J.; Pratt, R.H.

1979-01-01

An analytic perturbation theory developed previously is used to find a continuum screened-Coulomb wave function characterized by definite asymptotic momentum. This wave function satisfies an inhomogeneous partial differential equation which is solved in parabolic coordinates; the solution depends on both parabolic variables. We calculate partial wave projections of this solution and show that we can choose to add a solution of the homogeneous equation such that the partial wave projections become equal to the normalized continuum radial function found previously. However, finding the unique solution with given asymptotic linear momentum will require either using boundary conditions to determine the unique needed solution of the homogeneous equation or equivalently specifying the screened-Coulomb phase-shifts. (author)

On uniqueness in diffuse optical tomography

International Nuclear Information System (INIS)

Harrach, Bastian

2009-01-01

A prominent result of Arridge and Lionheart (1998 Opt. Lett. 23 882–4) demonstrates that it is in general not possible to simultaneously recover both the diffusion (aka scattering) and the absorption coefficient in steady-state (dc) diffusion-based optical tomography. In this work we show that it suffices to restrict ourselves to piecewise constant diffusion and piecewise analytic absorption coefficients to regain uniqueness. Under this condition both parameters can simultaneously be determined from complete measurement data on an arbitrarily small part of the boundary

Assessment of labour market returns in the case of gender unique human capital

OpenAIRE

Paas, Tiiu; Tverdostup, Maryna

2016-01-01

Maryna Tverdostup, Tiiu Paas, ERSA 2016: The paper focuses on the identification of the unique, non-reached by the opposite gender human capital and the analysis of its effect on the earning profiles of unique human capital holders. The overwhelming research aim is to better understand the possible reasons behind gender wage disparities, focusing on the unique features of male and female human capital and their returns. When assessing the gender pay disparities, variation of human capital cha...

Functional properties of hepatocytes in vitro are correlated with cell polarity maintenance.

Science.gov (United States)

Zeigerer, Anja; Wuttke, Anne; Marsico, Giovanni; Seifert, Sarah; Kalaidzidis, Yannis; Zerial, Marino

2017-01-01

Exploring the cell biology of hepatocytes in vitro could be a powerful strategy to dissect the molecular mechanisms underlying the structure and function of the liver in vivo. However, this approach relies on appropriate in vitro cell culture systems that can recapitulate the cell biological and metabolic features of the hepatocytes in the liver whilst being accessible to experimental manipulations. Here, we adapted protocols for high-resolution fluorescence microscopy and quantitative image analysis to compare two primary hepatocyte culture systems, monolayer and collagen sandwich, with respect to the distribution of two distinct populations of early endosomes (APPL1 and EEA1-positive), endocytic capacity, metabolic and signaling activities. In addition to the re-acquisition of hepatocellular polarity, primary hepatocytes grown in collagen sandwich but not in monolayer culture recapitulated the apico-basal distribution of EEA1 endosomes observed in liver tissue. We found that such distribution correlated with the organization of the actin cytoskeleton in vitro and, surprisingly, was dependent on the nutritional state in vivo. Hepatocytes in collagen sandwich also exhibited faster kinetics of low-density lipoprotein (LDL) and epidermal growth factor (EGF) internalization, showed improved insulin sensitivity and preserved their ability for glucose production, compared to hepatocytes in monolayer cultures. Although no in vitro culture system can reproduce the exquisite structural features of liver tissue, our data nevertheless highlight the ability of the collagen sandwich system to recapitulate key structural and functional properties of the hepatocytes in the liver and, therefore, support the usage of this system to study aspects of hepatocellular biology in vitro. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Unique battery with a multi-functional, physicochemically active membrane separator/electrolyte-electrode monolith and a method making the same

Science.gov (United States)

Gerald II, Rex E.; Ruscic, Katarina J.; Sears, Devin N.; Smith, Luis J.; Klingler, Robert J.; Rathke, Jerome W.

2012-07-24

The invention relates to a unique battery having a physicochemically active membrane separator/electrolyte-electrode monolith and method of making the same. The Applicant's invented battery employs a physicochemically active membrane separator/electrolyte-electrode that acts as a separator, electrolyte, and electrode, within the same monolithic structure. The chemical composition, physical arrangement of molecules, and physical geometry of the pores play a role in the sequestration and conduction of ions. In one preferred embodiment, ions are transported via the ion-hoping mechanism where the oxygens of the Al2O3 wall are available for positive ion coordination (i.e. Li+). This active membrane-electrode composite can be adjusted to a desired level of ion conductivity by manipulating the chemical composition and structure of the pore wall to either increase or decrease ion conduction.

Three Unique Implementations of Processes for PyCSP

DEFF Research Database (Denmark)

Friborg, Rune Møllegaard; Bjørndalen, John Markus; Vinter, Brian

2009-01-01

In this work we motivate and describe three unique implementations of processes for PyCSP: process, thread and greenlet based. The overall purpose is to demonstrate the feasibility of Communicating Sequential Processes as a framework for different application types and target platforms. The result...

Differentiating Performance Approach Goals and Their Unique Effects

Science.gov (United States)

Edwards, Ordene V.

2014-01-01

The study differentiates between two types of performance approach goals (competence demonstration performance approach goal and normative performance approach goal) by examining their unique effects on self-efficacy, interest, and fear of failure. Seventy-nine students completed questionnaires that measure performance approach goals,…

Biomolecule-functionalized polymer brushes.

Science.gov (United States)

Jiang, Hui; Xu, Fu-Jian

2013-04-21

Functional polymer brushes have been utilized extensively for the immobilization of biomolecules, which is of crucial importance for the development of biosensors and biotechnology. Recent progress in polymerization methods, in particular surface-initiated atom transfer radical polymerization (ATRP), has provided a unique means for the design and synthesis of new biomolecule-functionalized polymer brushes. This current review summarizes such recent research activities. The different preparation strategies for biomolecule immobilization through polymer brush spacers are described in detail. The functional groups of the polymer brushes used for biomolecule immobilization include epoxide, carboxylic acid, hydroxyl, aldehyde, and amine groups. The recent research activities indicate that functional polymer brushes become versatile and powerful spacers for immobilization of various biomolecules to maximize their functionalities. This review also demonstrates that surface-initiated ATRP is used more frequently than other polymerization methods in the designs of new biomolecule-functionalized polymer brushes.

Functional analysis and applications

CERN Document Server

Siddiqi, Abul Hasan

2018-01-01

This self-contained textbook discusses all major topics in functional analysis. Combining classical materials with new methods, it supplies numerous relevant solved examples and problems and discusses the applications of functional analysis in diverse fields. The book is unique in its scope, and a variety of applications of functional analysis and operator-theoretic methods are devoted to each area of application. Each chapter includes a set of problems, some of which are routine and elementary, and some of which are more advanced. The book is primarily intended as a textbook for graduate and advanced undergraduate students in applied mathematics and engineering. It offers several attractive features making it ideally suited for courses on functional analysis intended to provide a basic introduction to the subject and the impact of functional analysis on applied and computational mathematics, nonlinear functional analysis and optimization. It introduces emerging topics like wavelets, Gabor system, inverse pro...

Submodular functions and optimization

CERN Document Server

Fujishige, Satoru

2005-01-01

It has widely been recognized that submodular functions play essential roles in efficiently solvable combinatorial optimization problems. Since the publication of the 1st edition of this book fifteen years ago, submodular functions have been showing further increasing importance in optimization, combinatorics, discrete mathematics, algorithmic computer science, and algorithmic economics, and there have been made remarkable developments of theory and algorithms in submodular functions. The 2nd edition of the book supplements the 1st edition with a lot of remarks and with new two chapters: "Submodular Function Minimization" and "Discrete Convex Analysis." The present 2nd edition is still a unique book on submodular functions, which is essential to students and researchers interested in combinatorial optimization, discrete mathematics, and discrete algorithms in the fields of mathematics, operations research, computer science, and economics. Key features: - Self-contained exposition of the theory of submodular ...

Need for Uniqueness Determines Reactions to Web-Based Personalized Advertising.

Science.gov (United States)

Stiglbauer, Barbara; Kovacs, Carrie

2018-01-01

The presented empirical study among a sample of n = 256 participants addressed the relationship between consumers' need for uniqueness and their reactions to web-based personalized advertising. Drawing on regulatory focus theory, we argue that the consumers' need for uniqueness dimensions creative choice and similarity avoidance may relate to promotion and prevention regulatory orientations, respectively. Accordingly, we hypothesized that creative choice and similarity avoidance would differentially predict self-reported approach and avoidance behavior toward personalized advertising. These direct relationships were further expected to be mediated by subjective evaluations of personalized advertising (i.e., perceived value and irritation). In line with these hypotheses, we found that creative choice predicted approach behavior through increased web-based personalized advertising value, whereas similarity avoidance predicted avoidance behavior through increased irritation. Creative choice also predicted decreased irritation, which in turn was related to decreased approach behavior. In sum, the results suggest that the consumers' need for uniqueness dimensions should not be investigated as a composite, as they seem to reflect different regulatory orientations and are therefore likely to evoke different affective, cognitive, and behavioral responses.

Actualizing Unique Type and Token Values as a Solution to the Problem of Evil

Directory of Open Access Journals (Sweden)

Atle Ottesen Søvik

2017-12-01

Full Text Available Concerning the problem of evil, I suggest that God's goodness and omnipotence causes God to want to actualize many different values and things, not solely angels in heaven, but also type unique values like independence, self-formation, creativity, and surprise, and token unique goods like animals and human beings. Such a universe as ours, though, requires undisturbed indeterministic self-formation as actualized by a good God to give those token unique beings access to those type unique values and allow them the opportunity to live forever with God after completion of this self-formation.

A uniquely specialized ear in a very early tetrapod.

Science.gov (United States)

Clack, J A; Ahlberg, P E; Finney, S M; Dominguez Alonso, P; Robinson, J; Ketcham, R A

2003-09-04

The Late Devonian genus Ichthyostega was for many decades the earliest known tetrapod, and the sole representative of a transitional form between a fish and a land vertebrate. However, despite being known since 1932 (ref. 1) from a large collection of specimens, its morphology remained enigmatic and not what was expected of a very primitive tetrapod. Its apparent specializations led it to be considered as a "blind offshoot" or "sidebranch" off the tetrapod family tree, and recent cladistic analyses have disagreed about its exact phylogenetic position within the tetrapod stem group. In particular, its braincase and ear region defied interpretation, such that conventional anatomical terms seemed inapplicable. Using new material collected in 1998 (ref. 9), preparation of earlier-collected material, and high-resolution computed tomography scanning, here we identify and interpret these problematic anatomical structures. They can now be seen to form part of a highly specialized ear, probably a hearing device for use in water. This represents a structurally and functionally unique modification of the tetrapod otic region, unlike anything seen in subsequent tetrapod evolution. The presence of deeply grooved gill bars as in its contemporary Acanthostega suggest that Ichthyostega may have been more aquatically adapted than previously believed.

A Content Analysis of Unique Selling Propositions of Tobacco Print Ads

Science.gov (United States)

Shen, Megan Johnson; Banerjee, Smita C.; Greene, Kathryn; Carpenter, Amanda; Ostroff, Jamie S.

2017-01-01

Objectives The present study described the unique selling propositions (USPs) (propositions used to convince customers to use a particular brand/product by focusing on the unique benefit) of print tobacco ads. Methods A qualitative content analysis was conducted of print tobacco ads (N = 171) selected from August 2012-August 2013 for cigarettes, moist snuff, e-cigarettes, cigars, and snus to determine the content and themes of USPs for tobacco ads. Results Cigarette ad USP themes focused on portraying the product as attractive; moist snuff ads focused on portraying product as masculine; cigar ads focused on selling a “high end product;” and new and emerging tobacco products (e-cigarette, snus) focused on directly comparing these products to cigarettes. Conclusions Whereas traditional tobacco product ads used USPs focused on themes of enjoyment and pleasure (eg, attractive for cigarettes, “high end product” for cigars), new and emerging tobacco product ads offered the unique benefit (USP) of their product being a better and “safer” alternative to traditional tobacco products. Snuff’s USPs focused nearly exclusively on the masculinity of their products. Results of this study provide targets for potential tobacco regulatory actions that could be implemented to reduce demand for tobacco products by reducing their perceived unique benefits. PMID:28452697

Logic without unique readability - a study of semantic and syntactic ambiguity

DEFF Research Database (Denmark)

Bentzen, Martin Mose

One of the main reasons for introducing a formal language is to remove ambiguity, the possibility of assigning several meanings to a linguistic expression. Typically, this is achieved through ensuring unique readability of formulas by using brackets (or another convention, such as Polish notation...... not hold true universally. Whereas e.g. scope ambiguities in natural languages have been studied extensively, ambiguous formal languages have not been the focus of in depth research. Here, we lift the assumption of unique readability by omitting the brackets from propositional logic, making it possible...... to formally distinguish between syntactic and semantic ambiguity. A valuation then amounts to a semantic disambiguation, and rather than a unique valuation (truth value), there is a set of valuations corresponding to ways a formula could have been constructed. We show what happens to familiar concepts...

The Role of Visual Working Memory in Attentive Tracking of Unique Objects

Science.gov (United States)

Makovski, Tal; Jiang, Yuhong V.

2009-01-01

When tracking moving objects in space humans usually attend to the objects' spatial locations and update this information over time. To what extent do surface features assist attentive tracking? In this study we asked participants to track identical or uniquely colored objects. Tracking was enhanced when objects were unique in color. The benefit…

Non-unique factorizations algebraic, combinatorial and analytic theory

CERN Document Server

Geroldinger, Alfred

2006-01-01

From its origins in algebraic number theory, the theory of non-unique factorizations has emerged as an independent branch of algebra and number theory. Focused efforts over the past few decades have wrought a great number and variety of results. However, these remain dispersed throughout the vast literature. For the first time, Non-Unique Factorizations: Algebraic, Combinatorial, and Analytic Theory offers a look at the present state of the theory in a single, unified resource.Taking a broad look at the algebraic, combinatorial, and analytic fundamentals, this book derives factorization results and applies them in concrete arithmetical situations using appropriate transfer principles. It begins with a basic introduction that can be understood with knowledge of standard basic algebra. The authors then move to the algebraic theory of monoids, arithmetic theory of monoids, the structure of sets of lengths, additive group theory, arithmetical invariants, and the arithmetic of Krull monoids. They also provide a s...

Large anterior temporal Virchow-Robin spaces: unique MR imaging features

Energy Technology Data Exchange (ETDEWEB)

Lim, Anthony T. [Monash University, Neuroradiology Service, Monash Imaging, Monash Health, Melbourne, Victoria (Australia); Chandra, Ronil V. [Monash University, Neuroradiology Service, Monash Imaging, Monash Health, Melbourne, Victoria (Australia); Monash University, Department of Surgery, Faculty of Medicine, Nursing and Health Sciences, Melbourne (Australia); Trost, Nicholas M. [St Vincent' s Hospital, Neuroradiology Service, Melbourne (Australia); McKelvie, Penelope A. [St Vincent' s Hospital, Anatomical Pathology, Melbourne (Australia); Stuckey, Stephen L. [Monash University, Neuroradiology Service, Monash Imaging, Monash Health, Melbourne, Victoria (Australia); Monash University, Southern Clinical School, Faculty of Medicine, Nursing and Health Sciences, Melbourne (Australia)

2015-05-01

Large Virchow-Robin (VR) spaces may mimic cystic tumor. The anterior temporal subcortical white matter is a recently described preferential location, with only 18 reported cases. Our aim was to identify unique MR features that could increase prospective diagnostic confidence. Thirty-nine cases were identified between November 2003 and February 2014. Demographic, clinical data and the initial radiological report were retrospectively reviewed. Two neuroradiologists reviewed all MR imaging; a neuropathologist reviewed histological data. Median age was 58 years (range 24-86 years); the majority (69 %) was female. There were no clinical symptoms that could be directly referable to the lesion. Two thirds were considered to be VR spaces on the initial radiological report. Mean maximal size was 9 mm (range 5-17 mm); majority (79 %) had perilesional T2 or fluid-attenuated inversion recovery (FLAIR) hyperintensity. The following were identified as potential unique MR features: focal cortical distortion by an adjacent branch of the middle cerebral artery (92 %), smaller adjacent VR spaces (26 %), and a contiguous cerebrospinal fluid (CSF) intensity tract (21 %). Surgery was performed in three asymptomatic patients; histopathology confirmed VR spaces. Unique MR features were retrospectively identified in all three patients. Large anterior temporal lobe VR spaces commonly demonstrate perilesional T2 or FLAIR signal and can be misdiagnosed as cystic tumor. Potential unique MR features that could increase prospective diagnostic confidence include focal cortical distortion by an adjacent branch of the middle cerebral artery, smaller adjacent VR spaces, and a contiguous CSF intensity tract. (orig.)

Fish functional groups in a tropical wetland of the Yucatan Peninsula, Mexico

Directory of Open Access Journals (Sweden)

Fernando Córdova-Tapia

Full Text Available ABSTRACT The characterization of species' functional traits is a major step in the understanding and description of communities in natural habitats. The classification of species into functional groups is a useful tool to identify redundancy and uniqueness. We studied the fish community of a pristine freshwater wetland in the Sian Ka'an Biosphere Reserve by analysing two multidimensional functions: food acquisition and locomotion. We investigated changes in the functional group structure between habitats (permanent and temporary pools and seasons (dry and wet. Six functional groups with different ecological characteristics were detected, two of which had high functional redundancy and three of them were represented by single species with unique ecological functions. In permanent pools during the dry season, functional group richness and diversity were lower, while evenness was higher. During the wet season, all functional groups were detected and similar functional group structure was found between habitats. These results suggest an effect of environmental filtering during the dry season and niche complementarity during the wet season.

Comments on the locality in density-functional theory

International Nuclear Information System (INIS)

Lindgren, Ingvar; Salomonson, Sten

2003-01-01

The 'locality hypothesis' in density-functional theory (DFT), implying that the functional derivative is equivalent to a multiplicative local function, forms the basis of models of Kohn-Sham type. This has been generally accepted by the community since the advent of the model, and has later been formally proved for a large class of functionals. The hypothesis has recently been questioned by Nesbet [Phys. Rev. A 58, R12 (1998) and Phys. Rev. A 65, 010502 (2001)], who claims that it fails for the kinetic-energy functional for a system with more than two noninteracting electrons with a nondegenerate ground state. This conclusion has been questioned by Gal [Phys. Rev. A 62, 044501 (2000)] and by Holas and March [Phys. Rev. A 64, 016501 (2001)]. We claim that the arguments of Nesbet are incorrect, since the orbital functional used for the kinetic energy is not a unique functional of the total density in the domain of unnormalized orbitals. We have demonstrated that with a proper definition of the kinetic energy, which is a unique density functional also in the unnormalized region, the derivative can be represented by a single local multiplicative function for all v-representable densities. Therefore, we consider the controversy connected with the issue raised by Nesbet as resolved. We believe that the proof of the differentiability given here can be extended to larger groups of DFT functionals, and works along these lines are in progress

Protein nanoparticle: A unique system as drug delivery vehicles

African Journals Online (AJOL)

STORAGESEVER

2008-12-29

Dec 29, 2008 ... Nanobiotechnology Research Center, Faculty of Chemical Engineering, Babol University of Technology, Iran. ... as potential carriers with unique advantages including ..... for intracellular uptake in BT/20 human breast cancer.

Partial covariance based functional connectivity computation using Ledoit-Wolf covariance regularization.

Science.gov (United States)

Brier, Matthew R; Mitra, Anish; McCarthy, John E; Ances, Beau M; Snyder, Abraham Z

2015-11-01

Functional connectivity refers to shared signals among brain regions and is typically assessed in a task free state. Functional connectivity commonly is quantified between signal pairs using Pearson correlation. However, resting-state fMRI is a multivariate process exhibiting a complicated covariance structure. Partial covariance assesses the unique variance shared between two brain regions excluding any widely shared variance, hence is appropriate for the analysis of multivariate fMRI datasets. However, calculation of partial covariance requires inversion of the covariance matrix, which, in most functional connectivity studies, is not invertible owing to rank deficiency. Here we apply Ledoit-Wolf shrinkage (L2 regularization) to invert the high dimensional BOLD covariance matrix. We investigate the network organization and brain-state dependence of partial covariance-based functional connectivity. Although RSNs are conventionally defined in terms of shared variance, removal of widely shared variance, surprisingly, improved the separation of RSNs in a spring embedded graphical model. This result suggests that pair-wise unique shared variance plays a heretofore unrecognized role in RSN covariance organization. In addition, application of partial correlation to fMRI data acquired in the eyes open vs. eyes closed states revealed focal changes in uniquely shared variance between the thalamus and visual cortices. This result suggests that partial correlation of resting state BOLD time series reflect functional processes in addition to structural connectivity. Copyright © 2015 Elsevier Inc. All rights reserved.

Disruption of endocytic trafficking in frontotemporal dementia with CHMP2B mutations

DEFF Research Database (Denmark)

Urwin, Hazel; Authier, Astrid; Nielsen, Jørgen Erik

2010-01-01

Mutations in CHMP2B cause frontotemporal dementia (FTD) in a large Danish pedigree, which is termed FTD linked to chromosome 3 (FTD-3), and also in an unrelated familial FTD patient. CHMP2B is a component of the ESCRT-III complex, which is required for function of the multivesicular body (MVB), a...

Unique features of space reactors

International Nuclear Information System (INIS)

Buden, D.

1990-01-01

This paper reports on space reactors that are designed to meet a unique set of requirements; they must be sufficiently compact to be launched in a rocket to their operational location, operate for many years without maintenance and servicing, operate in extreme environments, and reject heat by radiation to space. To meet these restrictions, operating temperatures are much greater than in terrestrial power plants, and the reactors tend to have a fast neutron spectrum. Currently, a new generation of space reactor power plants is being developed. The major effort is in the SP-100 program, where the power plant is being designed for seven years of full power, and no maintenance operation at a reactor outlet operating temperature of 1350 K

Dramatic pretend play games uniquely improve emotional control in young children.

Science.gov (United States)

Goldstein, Thalia R; Lerner, Matthew D

2017-09-15

Pretense is a naturally occurring, apparently universal activity for typically developing children. Yet its function and effects remain unclear. One theorized possibility is that pretense activities, such as dramatic pretend play games, are a possible causal path to improve children's emotional development. Social and emotional skills, particularly emotional control, are critically important for social development, as well as academic performance and later life success. However, the study of such approaches has been criticized for potential bias and lack of rigor, precluding the ability to make strong causal claims. We conducted a randomized, component control (dismantling) trial of dramatic pretend play games with a low-SES group of 4-year-old children (N = 97) to test whether such practice yields generalized improvements in multiple social and emotional outcomes. We found specific effects of dramatic play games only on emotional self-control. Results suggest that dramatic pretend play games involving physicalizing emotional states and traits, pretending to be animals and human characters, and engaging in pretend scenarios in a small group may improve children's emotional control. These findings have implications for the function of pretense and design of interventions to improve emotional control in typical and atypical populations. Further, they provide support for the unique role of dramatic pretend play games for young children, particularly those from low-income backgrounds. A video abstract of this article can be viewed at: https://youtu.be/2GVNcWKRHPk. © 2017 John Wiley & Sons Ltd.

Unique and analogous functions of aquaporin O for fiber cell architecture and ocular lens transparency

Energy Technology Data Exchange (ETDEWEB)

Kumari, S.S.; Eswaramoorthy, S.; Mathias, R. T.; Varadaraj, K.

2011-09-01

Aquaporin (AQP) 1 and AQP0 water channels are expressed in lens epithelial and fiber cells, respectively, facilitating fluid circulation for nourishing the avascular lens to maintain transparency. Even though AQP0 water permeability is 40-fold less than AQP1, AQP0 is selectively expressed in the fibers. Delimited AQP0 fiber expression is attributed to a unique structural role as an adhesion protein. To validate this notion, we determined if wild type (WT) lens ultrastructure and fibercell adhesion are different in AQP0{sup -/-}, and TgAQP1{sup +/+}/AQP0{sup -/-} mice that transgenically express AQP1 (TgAQP1) in fibercells without AQP0 (AQP0{sup -/-}). In WT, lenses were transparent with 'Y' sutures. Fibers contained opposite end curvature, lateral interdigitations, hexagonal shape, and were arranged as concentric growth shells. AQP0{sup -/-}lenses were cataractous, lacked 'Y' sutures, ordered packing and well-defined lateral interdigitations. TgAQP1{sup +/+}/AQP0{sup -/-} lenses showed improvement in transparency and lateral interdigitations in the outer cortex while inner cortex and nuclear fibers were severely disintegrated. Transmission electron micrographs exhibited tightly packed fibercells in WT whereas AQP0{sup -/-} and TgAQP1{sup +/+}/AQP0{sup -/-}lenses had wide extracellular spaces. Fibers were easily separable by teasing in AQP0{sup -/-} and TgAQP1{sup +/+}/AQP0{sup -/-}lenses compared to WT. Our data suggest that the increased water permeability through AQP1 does not compensate for loss of AQP0 expression in TgAQP1{sup +/+}/AQP0{sup -/-} mice. Fibercell AQP0 expression is required to maintain their organization, which is a requisite for lenstransparency. AQP0 appears necessary for cell-to-cell adhesion and thereby to minimize light scattering since in the AQP0{sup -/-} and TgAQP1{sup +/+}/AQP0{sup -/-} lenses, fiber cell disorganization was evident.

NHash: Randomized N-Gram Hashing for Distributed Generation of Validatable Unique Study Identifiers in Multicenter Research.

Science.gov (United States)

Zhang, Guo-Qiang; Tao, Shiqiang; Xing, Guangming; Mozes, Jeno; Zonjy, Bilal; Lhatoo, Samden D; Cui, Licong

2015-11-10

A unique study identifier serves as a key for linking research data about a study subject without revealing protected health information in the identifier. While sufficient for single-site and limited-scale studies, the use of common unique study identifiers has several drawbacks for large multicenter studies, where thousands of research participants may be recruited from multiple sites. An important property of study identifiers is error tolerance (or validatable), in that inadvertent editing mistakes during their transmission and use will most likely result in invalid study identifiers. This paper introduces a novel method called "Randomized N-gram Hashing (NHash)," for generating unique study identifiers in a distributed and validatable fashion, in multicenter research. NHash has a unique set of properties: (1) it is a pseudonym serving the purpose of linking research data about a study participant for research purposes; (2) it can be generated automatically in a completely distributed fashion with virtually no risk for identifier collision; (3) it incorporates a set of cryptographic hash functions based on N-grams, with a combination of additional encryption techniques such as a shift cipher; (d) it is validatable (error tolerant) in the sense that inadvertent edit errors will mostly result in invalid identifiers. NHash consists of 2 phases. First, an intermediate string using randomized N-gram hashing is generated. This string consists of a collection of N-gram hashes f1, f2, ..., fk. The input for each function fi has 3 components: a random number r, an integer n, and input data m. The result, fi(r, n, m), is an n-gram of m with a starting position s, which is computed as (r mod |m|), where |m| represents the length of m. The output for Step 1 is the concatenation of the sequence f1(r1, n1, m1), f2(r2, n2, m2), ..., fk(rk, nk, mk). In the second phase, the intermediate string generated in Phase 1 is encrypted using techniques such as shift cipher. The result

A Unique Case of Muscle Invasive Metastatic Breast Cancer Mimicking Myositis

Science.gov (United States)

2017-06-28

TYPE 08/ 03/20 17 Publ ication/Journal 4. TITLE AND SUBTITLE A unique case of muscle-invasive metastatic breast cancer mimicking myositis 6...Rev. 8/98) Prescnbed by ANSI Std Z39. 18 Adobe Profes11on11 7.0 Title: A Unique Case of M uscle-Invasive Metastatic Breast Cancer M imicking...an 84-year-old female who presented with neck swelling and upper airway obstruction due to metastatic breast cancer invading the sternocleidomastoid

Exposure to the BPA-Substitute Bisphenol S Causes Unique Alterations of Germline Function.

Directory of Open Access Journals (Sweden)

Yichang Chen

2016-07-01

Full Text Available Concerns about the safety of Bisphenol A, a chemical found in plastics, receipts, food packaging and more, have led to its replacement with substitutes now found in a multitude of consumer products. However, several popular BPA-free alternatives, such as Bisphenol S, share a high degree of structural similarity with BPA, suggesting that these substitutes may disrupt similar developmental and reproductive pathways. We compared the effects of BPA and BPS on germline and reproductive functions using the genetic model system Caenorhabditis elegans. We found that, similarly to BPA, BPS caused severe reproductive defects including germline apoptosis and embryonic lethality. However, meiotic recombination, targeted gene expression, whole transcriptome and ontology analyses as well as ToxCast data mining all indicate that these effects are partly achieved via mechanisms distinct from BPAs. These findings therefore raise new concerns about the safety of BPA alternatives and the risk associated with human exposure to mixtures.

Recovery of the Dirac system from the rectangular Weyl matrix function

International Nuclear Information System (INIS)

Fritzsche, B; Kirstein, B; Roitberg, I Ya; Sakhnovich, A L

2012-01-01

Weyl theory for Dirac systems with rectangular matrix potentials is non-classical. The corresponding Weyl functions are rectangular matrix functions. Furthermore, they are non-expansive in the upper semi-plane. Inverse problems are studied for such Weyl functions, and some results are new even for the square Weyl functions. High-energy asymptotics of Weyl functions and Borg–Marchenko-type uniqueness results are derived too. (paper)

Examination of brain function using PET and SPECT

Energy Technology Data Exchange (ETDEWEB)

Sasaki, Yasuhito; Momose, Toshinitsu; Watanabe, Toshiaki; Oku, Shinya; Nishikawa, Junichi [Tokyo Univ. (Japan). Faculty of Medicine

1996-12-31

The purpose of the presentation is to elucidate the unique role of PET (positron emission computed tomography) and SPECT (single photon emission computed tomography) in assessing physiological and biochemical functions of the brain.

Nanosized complexation assemblies housed inside reverse micelles churn out monocytic delivery cores for bendamustine hydrochloride.

Science.gov (United States)

Singh, Yuvraj; Chandrashekhar, Anumandla; Meher, Jaya Gopal; Durga Rao Viswanadham, K K; Pawar, Vivek K; Raval, Kavit; Sharma, Komal; Singh, Pankaj K; Kumar, Animesh; Chourasia, Manish K

2017-04-01

We explore a plausible method of targeting bendamustine hydrochloride (BM) to circulatory monocytes by exploiting their intrinsic endocytic/phagocytic capability. We do so by complexation of sodium alginate and chitosan inside dioctyl sulfo succinate sodium (AOT) reverse micelles to form bendamustine hydrochloride loaded nanoparticles (CANPs). Dynamic light scattering, electrophoretic mobility and UV spectroscopy were used to detail intra-micellar complexation dynamics and to prove that drug was co-captured during interaction of carbohydrate polymers. A fluorescent conjugate of drug (RBM) was used to trace its intracellular fate after its loading into nanoparticles. CANPs were sized below 150nm, had 75% drug entrapment and negative zeta potential (-30mV). Confocal microscopy demonstrated that developed chitosan alginate nanoparticles had the unique capability to carry BM specifically to its site of action. Quantitative and mechanism based cell uptake studies revealed that monocytes had voracious capacity to internalize CANPs via simultaneous scavenger receptor based endocytic and phagocytic mechanism. Comparative in vitro pharmacokinetic studies revealed obtainment of significantly greater intracellular drug levels when cells were treated with CANPs. This caused reduction in IC 50 (22.5±2.1μg/mL), enhancement in G 2 M cell cycle arrest, greater intracellular reactive oxygen species generation, and increased apopotic potential of bendamustine hydrochloride in THP-1 cells. Selective monocytic targeting of bendamustine hydrochloride using carbohydrate constructs can prove advantageous in case of leukemic disorders displaying overabundance of such cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Uniqueness and numerical methods in inverse obstacle scattering

International Nuclear Information System (INIS)

Kress, Rainer

2007-01-01

The inverse problem we consider in this tutorial is to determine the shape of an obstacle from the knowledge of the far field pattern for scattering of time-harmonic plane waves. In the first part we will concentrate on the issue of uniqueness, i.e., we will investigate under what conditions an obstacle and its boundary condition can be identified from a knowledge of its far field pattern for incident plane waves. We will review some classical and some recent results and draw attention to open problems. In the second part we will survey on numerical methods for solving inverse obstacle scattering problems. Roughly speaking, these methods can be classified into three groups. Iterative methods interpret the inverse obstacle scattering problem as a nonlinear ill-posed operator equation and apply iterative schemes such as regularized Newton methods, Landweber iterations or conjugate gradient methods for its solution. Decomposition methods, in principle, separate the inverse scattering problem into an ill-posed linear problem to reconstruct the scattered wave from its far field and the subsequent determination of the boundary of the scatterer from the boundary condition. Finally, the third group consists of the more recently developed sampling methods. These are based on the numerical evaluation of criteria in terms of indicator functions that decide whether a point lies inside or outside the scatterer. The tutorial will give a survey by describing one or two representatives of each group including a discussion on the various advantages and disadvantages

Counting with symmetric functions

CERN Document Server

Mendes, Anthony

2015-01-01

This monograph provides a self-contained introduction to symmetric functions and their use in enumerative combinatorics.  It is the first book to explore many of the methods and results that the authors present. Numerous exercises are included throughout, along with full solutions, to illustrate concepts and also highlight many interesting mathematical ideas. The text begins by introducing fundamental combinatorial objects such as permutations and integer partitions, as well as generating functions.  Symmetric functions are considered in the next chapter, with a unique emphasis on the combinatorics of the transition matrices between bases of symmetric functions.  Chapter 3 uses this introductory material to describe how to find an assortment of generating functions for permutation statistics, and then these techniques are extended to find generating functions for a variety of objects in Chapter 4.  The next two chapters present the Robinson-Schensted-Knuth algorithm and a method for proving Pólya’s enu...

Evolutionary theory, human uniqueness and the image of God

Directory of Open Access Journals (Sweden)

Gijsbert van den Brink

2012-10-01

Full Text Available In this article, I examined what might be called the evolutionary argument against human uniqueness and human dignity. After having rehearsed briefly the roots of the classical Judeo- Christian view on human uniqueness and human dignity in the first chapters of Genesis, I went on to explore and delineate the nature of the evolutionary argument against this view. Next, I examined whether Christian theology might widen the concept of imago Dei so as to include other beings as well as humans, thus giving up the idea of human uniqueness. I concluded, however, that this move is deeply problematic. Therefore, I turned to a discussion of some recent attempts to define both human uniqueness and the image of God in theological rather than empirical terms. One of these, which is based on the concept of incarnation, is found wanting, but another one is construed in such a way that it enables us to reconcile the idea of human uniqueness as encapsulated in the doctrine of the imago Dei with contemporary evolutionary theory. Thus, this article can be seen as an exercise in bringing classical Christian theology to terms with evolution, further highlighting this theology’s ongoing vitality. Evolusieteorie, menslike uniekheid and die beeld van God. In hierdie artikel ondersoek ek die sogenaamde evolusionêre argument teen menslike uniekheid en menswaardigheid. Na ‘n kort oorsig oor die oorsprong van die klassieke Joods-Christelike siening van menslike uniekheid en menswaardigheid soos uit die eerste vyf hoofstukke van Genesis blyk, ondersoek en beeld ek die aard van die evolusionêre argument hierteenoor uit. Vervolgens word die vraag ondersoek of die Christelike teologie die konsep van imago Dei sodanig kan verbreed dat dit ook ander wesens behalwe mense kan insluit, waardeur die idee van menslike uniekheid dus prysgegee word. Ek kom egter tot die slotsom dat hierdie skuif hoogs problematies is. Daarom wend ek my tot ’n bespreking van onlangse pogings om

Target Choice and Unique Synergies in Global Mobile Telephony

DEFF Research Database (Denmark)

Claussen, Jörg; Köhler, Rebecca; Kretschmer, Tobias

2018-01-01

their foresight to select specific targets: First, they lower integration costs by selecting geographically close targets. This effect is stronger when buyer and target are in the same country, but only if the market is not so concentrated that it provokes regulatory interventions. Second, they select targets......The success of acquisitions rests on detecting and realizing unique synergies between buyer and target through their dyadic relationships. We study the role of unique dyad-specific synergies in the selection of takeover targets in the global mobile telecommunications industry. Firms use...... that can be acquired at a modest bid premium because they have asymmetric bargaining power. Finally, they select targets which can generate significant synergies due to technological synergies. Our work expands the existing target selection literature by studying dyad-specific factors within a single...

Unique Outcomes in the Narratives of Young Adults Who Experienced Dating Violence as Adolescents.

Science.gov (United States)

Draucker, Claire Burke; Smith, Carolyn; Mazurczyk, Jill; Thomas, Destini; Ramirez, Patricia; McNealy, Kim; Thomas, Jade; Martsolf, Donna S

2016-01-01

Narrative therapy, an approach based on the reauthoring of life narratives, may be a useful psychotherapeutic strategy for youth who have experienced dating violence. A cornerstone of narrative therapy is the concept of unique outcomes, which are moments that stand in contrast to a client's otherwise problem-saturated narratives. The purpose of this study was to identify and categorize unique outcomes embedded in narratives about adolescent dating violence. Text units representing unique outcomes were extracted from transcripts of interviews with 88 young adults who had experienced dating violence and were categorized using standard content analytic techniques. Six categories of unique outcome stories were identified: facing-facts stories, standing-up-for-myself stories, cutting-it-off stories, cutting-'em-loose stories, getting-back-on-track stories, and changing-it-up stories. This typology of unique outcomes can inform clinicians who work with clients who have a history of adolescent dating violence. © The Author(s) 2015.

Constructing a unique two-phase compressibility factor model for lean gas condensates

Energy Technology Data Exchange (ETDEWEB)

Moayyedi, Mahmood; Gharesheikhlou, Aliashghar [Research Institute of Petroleum Industry (RIPI), Tehran (Iran, Islamic Republic of); Azamifard, Arash; Mosaferi, Emadoddin [Amirkabir University of Technology (AUT), Tehran (Iran, Islamic Republic of)

2015-02-15

Generating a reliable experimental model for two-phase compressibility factor in lean gas condensate reservoirs has always been demanding, but it was neglected due to lack of required experimental data. This study presents the main results of constructing the first two-phase compressibility factor model that is completely valid for Iranian lean gas condensate reservoirs. Based on a wide range of experimental data bank for Iranian lean gas condensate reservoirs, a unique two-phase compressibility factor model was generated using design of experiments (DOE) method and neural network technique (ANN). Using DOE, a swift cubic response surface model was generated for two-phase compressibility factor as a function of some selected fluid parameters for lean gas condensate fluids. The proposed DOE and ANN models were finally validated using four new independent data series. The results showed that there is a good agreement between experimental data and the proposed models. In the end, a detailed comparison was made between the results of proposed models.

Constructing a unique two-phase compressibility factor model for lean gas condensates

International Nuclear Information System (INIS)

Moayyedi, Mahmood; Gharesheikhlou, Aliashghar; Azamifard, Arash; Mosaferi, Emadoddin

2015-01-01

Generating a reliable experimental model for two-phase compressibility factor in lean gas condensate reservoirs has always been demanding, but it was neglected due to lack of required experimental data. This study presents the main results of constructing the first two-phase compressibility factor model that is completely valid for Iranian lean gas condensate reservoirs. Based on a wide range of experimental data bank for Iranian lean gas condensate reservoirs, a unique two-phase compressibility factor model was generated using design of experiments (DOE) method and neural network technique (ANN). Using DOE, a swift cubic response surface model was generated for two-phase compressibility factor as a function of some selected fluid parameters for lean gas condensate fluids. The proposed DOE and ANN models were finally validated using four new independent data series. The results showed that there is a good agreement between experimental data and the proposed models. In the end, a detailed comparison was made between the results of proposed models

Mechanics of advanced functional materials

CERN Document Server

Wang, Biao

2013-01-01

Mechanics of Advanced Functional Materials emphasizes the coupling effect between the electric and mechanical field in the piezoelectric, ferroelectric and other functional materials. It also discusses the size effect on the ferroelectric domain instability and phase transition behaviors using the continuum micro-structural evolution models. Functional materials usually have a very wide application in engineering due to their unique thermal, electric, magnetic, optoelectronic, etc., functions. Almost all the applications demand that the material should have reasonable stiffness, strength, fracture toughness and the other mechanical properties. Furthermore, usually the stress and strain fields on the functional materials and devices have some important coupling effect on the functionality of the materials. Much progress has been made concerning the coupling electric and mechanical behaviors such as the coupled electric and stress field distribution in piezoelectric solids, ferroelectric domain patterns in ferr...

Uniqueness of the joint measurement and the structure of the set of compatible quantum measurements

Science.gov (United States)

Guerini, Leonardo; Terra Cunha, Marcelo

2018-04-01

We address the problem of characterising the compatible tuples of measurements that admit a unique joint measurement. We derive a uniqueness criterion based on the method of perturbations and apply it to show that extremal points of the set of compatible tuples admit a unique joint measurement, while all tuples that admit a unique joint measurement lie in the boundary of such a set. We also provide counter-examples showing that none of these properties are both necessary and sufficient, thus completely describing the relation between the joint measurement uniqueness and the structure of the compatible set. As a by-product of our investigations, we completely characterise the extremal and boundary points of the set of general tuples of measurements and of the subset of compatible tuples.

Parental Expressivity and Parenting Styles in Chinese Families: Prospective and Unique Relations to Children’s Psychological Adjustment

Science.gov (United States)

Chen, Stephen H.; Zhou, Qing; Eisenberg, Nancy; Valiente, Carlos; Wang, Yun

2012-01-01

SYNOPSIS Objectives Parents from different cultures differ in how frequently they express emotions. However, the generalizability of the relations between parental expressivity and child adjustment in non-Western cultures has not been extensively studied. The goal of the present study was to investigate prospective relations between parental expressivity within the family (positive, negative dominant, and negative submissive expressivity) and Chinese children’s psychological adjustment, above and beyond parenting styles. Design The study used two waves (3.8 years apart) of longitudinal data from a sample (n= 425) of children in Beijing (mean ages = 7.7 years at T1 and 11.6 years at T2). Parental expressivity and parenting styles were self-reported. To reduce the potential measurement overlap, items that tap parental expression of emotions toward the child were removed from the parenting style measure. Children’s adjustment was measured with parents’, teachers’, and peers’ or children’s reports. Results Consistent with findings with European American samples, parental negative dominant expressivity uniquely and positively predicted Chinese children’s externalizing problems controlling for prior externalizing problems, parenting styles, and family SES. Neither parental expressivity nor parenting styles uniquely predicted social competence. Conclusions Despite previously reported cultural differences in the mean levels of parental expressivity, some of the socialization functions of parental expressivity found in Western countries can be generalized to Chinese families. Although parental expressivity and parenting styles are related constructs, their unique relations to child’s adjustment suggest that they should be examined as distinct processes. PMID:23226715

Secondary metabolites from the unique bamboo, Melocanna baccifera.

Science.gov (United States)

Govindan, Balaji; Johnson, Anil John; Viswanathan, Gayathri; Ramaswamy, Venkataraman; Koshy, Konnath Chacko; Baby, Sabulal

2018-02-15

Phytochemistry of fruits and leaves of the unique bamboo Melocanna baccifera resulted in the isolation of 27 secondary metabolites, including 4-Oxabicyclo[3.2.2]nona-1(7),5,8-triene and Verbacine. Biological activity studies of Verbacine revealed it as an inhibitor of acetylcholinesterase and as cytotoxic against C6 cancer cells.

Klf15 Is Critical for the Development and Differentiation of Drosophila Nephrocytes.

Directory of Open Access Journals (Sweden)

Jessica R Ivy

Full Text Available Insect nephrocytes are highly endocytic scavenger cells that represent the only invertebrate model for the study of human kidney podocytes. Despite their importance, nephrocyte development is largely uncharacterised. This work tested whether the insect ortholog of mammalian Kidney Krüppel-Like Factor (Klf15, a transcription factor required for mammalian podocyte differentiation, was required for insect nephrocyte development. It was found that expression of Drosophila Klf15 (dKlf15, previously known as Bteb2 was restricted to the only two nephrocyte populations in Drosophila, the garland cells and pericardial nephrocytes. Loss of dKlf15 function led to attrition of both nephrocyte populations and sensitised larvae to the xenotoxin silver nitrate. Although pericardial nephrocytes in dKlf15 loss of function mutants were specified during embryogenesis, they failed to express the slit diaphragm gene sticks and stones and did not form slit diaphragms. Conditional silencing of dKlf15 in adults led to reduced surface expression of the endocytic receptor Amnionless and loss of in vivo scavenger function. Over-expression of dKlf15 increased nephrocyte numbers and rescued age-dependent decline in nephrocyte function. The data place dKlf15 upstream of sns and Amnionless in a nephrocyte-restricted differentiation pathway and suggest dKlf15 expression is both necessary and sufficient to sustain nephrocyte differentiation. These findings explain the physiological relevance of dKlf15 in Drosophila and imply that the role of KLF15 in human podocytes is evolutionarily conserved.

Determining hydraulic parameters of a karst aquifer using unique ...

African Journals Online (AJOL)

2014-07-15

Jul 15, 2014 ... 1 Faculty of Natural Sciences, Potchefstroom Campus, North-West University, ... a first-ever attempt to utilise various sets of unique historical data ..... Even though the aquifer shows characteristics of all major ...... Earth Sci.

Symmetry breaking and uniqueness for the incompressible Navier-Stokes equations

International Nuclear Information System (INIS)

Dascaliuc, Radu; Thomann, Enrique; Waymire, Edward C.; Michalowski, Nicholas

2015-01-01

The present article establishes connections between the structure of the deterministic Navier-Stokes equations and the structure of (similarity) equations that govern self-similar solutions as expected values of certain naturally associated stochastic cascades. A principle result is that explosion criteria for the stochastic cascades involved in the probabilistic representations of solutions to the respective equations coincide. While the uniqueness problem itself remains unresolved, these connections provide interesting problems and possible methods for investigating symmetry breaking and the uniqueness problem for Navier-Stokes equations. In particular, new branching Markov chains, including a dilogarithmic branching random walk on the multiplicative group (0, ∞), naturally arise as a result of this investigation

Symmetry breaking and uniqueness for the incompressible Navier-Stokes equations.

Science.gov (United States)

Dascaliuc, Radu; Michalowski, Nicholas; Thomann, Enrique; Waymire, Edward C

2015-07-01

The present article establishes connections between the structure of the deterministic Navier-Stokes equations and the structure of (similarity) equations that govern self-similar solutions as expected values of certain naturally associated stochastic cascades. A principle result is that explosion criteria for the stochastic cascades involved in the probabilistic representations of solutions to the respective equations coincide. While the uniqueness problem itself remains unresolved, these connections provide interesting problems and possible methods for investigating symmetry breaking and the uniqueness problem for Navier-Stokes equations. In particular, new branching Markov chains, including a dilogarithmic branching random walk on the multiplicative group (0, ∞), naturally arise as a result of this investigation.

Stationary Black Holes: Uniqueness and Beyond

Directory of Open Access Journals (Sweden)

Heusler Markus

1998-01-01

Full Text Available The spectrum of known black hole solutions to the stationary Einstein equations has increased in an unexpected way during the last decade. In particular, it has turned out that not all black hole equilibrium configurations are characterized by their mass, angular momentum and global charges. Moreover, the high degree of symmetry displayed by vacuum and electro-vacuum black hole space-times ceases to exist in self-gravitating non-linear field theories. This text aims to review some of the recent developments and to discuss them in the light of the uniqueness theorem for the Einstein-Maxwell system.

Stationary Black Holes: Uniqueness and Beyond

Directory of Open Access Journals (Sweden)

Piotr T. Chruściel

2012-05-01

Full Text Available The spectrum of known black-hole solutions to the stationary Einstein equations has been steadily increasing, sometimes in unexpected ways. In particular, it has turned out that not all black-hole-equilibrium configurations are characterized by their mass, angular momentum and global charges. Moreover, the high degree of symmetry displayed by vacuum and electro vacuum black-hole spacetimes ceases to exist in self-gravitating non-linear field theories. This text aims to review some developments in the subject and to discuss them in light of the uniqueness theorem for the Einstein-Maxwell system.

Generalized Functions for the Fractional Calculus

Science.gov (United States)

Lorenzo, Carl F.; Hartley, Tom T.

1999-01-01

Previous papers have used two important functions for the solution of fractional order differential equations, the Mittag-Leffler functionE(sub q)[at(exp q)](1903a, 1903b, 1905), and the F-function F(sub q)[a,t] of Hartley & Lorenzo (1998). These functions provided direct solution and important understanding for the fundamental linear fractional order differential equation and for the related initial value problem (Hartley and Lorenzo, 1999). This paper examines related functions and their Laplace transforms. Presented for consideration are two generalized functions, the R-function and the G-function, useful in analysis and as a basis for computation in the fractional calculus. The R-function is unique in that it contains all of the derivatives and integrals of the F-function. The R-function also returns itself on qth order differ-integration. An example application of the R-function is provided. A further generalization of the R-function, called the G-function brings in the effects of repeated and partially repeated fractional poles.

Child Functional Independence and Maternal Psychosocial Stress as Risk Factors Threatening Adaptation in Mothers of Physically or Sensorially Handicapped Children.

Science.gov (United States)

Wallander, Jan L; And Others

1990-01-01

Investigated contribution of child functional independence and maternal psychosocial stress to adaptation of 119 mothers of physically or sensorially handicapped children between the ages of 2 and 18. Child functional independence did not uniquely explain variation in mothers' adaptation. Maternal stress was uniquely associated with maternal…

Functional Properties of Microorganisms in Fermented Foods

Directory of Open Access Journals (Sweden)

Jyoti Prakash Tamang

2016-04-01

Full Text Available Fermented foods have unique functional properties imparting some health benefits to consumers due to presence of functional microorganisms, which possess probiotics properties, antimicrobial, antioxidant, peptide production, etc. Health benefits of some global fermented foods are synthesis of nutrients, prevention of cardiovascular disease, prevention of cancer, gastrointestinal disorders, allergic reactions, diabetes, among others. The present paper is aimed to review the information on some functional properties of the microorganisms associated with fermented foods and beverages, and their health-promoting benefits to consumers.

Linear measure functional differential equations with infinite delay

OpenAIRE

Monteiro, G. (Giselle Antunes); Slavík, A.

2014-01-01

We use the theory of generalized linear ordinary differential equations in Banach spaces to study linear measure functional differential equations with infinite delay. We obtain new results concerning the existence, uniqueness, and continuous dependence of solutions. Even for equations with a finite delay, our results are stronger than the existing ones. Finally, we present an application to functional differential equations with impulses.

Self-Amplifying Replicon RNA Vaccine Delivery to Dendritic Cells by Synthetic Nanoparticles

Directory of Open Access Journals (Sweden)

Kenneth C. McCullough

2014-10-01

Full Text Available Dendritic cells (DC play essential roles determining efficacy of vaccine delivery with respect to immune defence development and regulation. This renders DCs important targets for vaccine delivery, particularly RNA vaccines. While delivery of interfering RNA oligonucleotides to the appropriate intracellular sites for RNA-interference has proven successful, the methodologies are identical for RNA vaccines, which require delivery to RNA translation sites. Delivery of mRNA has benefitted from application of cationic entities; these offer value following endocytosis of RNA, when cationic or amphipathic properties can promote endocytic vesicle membrane perturbation to facilitate cytosolic translocation. The present review presents how such advances are being applied to the delivery of a new form of RNA vaccine, replicons (RepRNA carrying inserted foreign genes of interest encoding vaccine antigens. Approaches have been developed for delivery to DCs, leading to the translation of the RepRNA and encoded vaccine antigens both in vitro and in vivo. Potential mechanisms favouring efficient delivery leading to translation are discussed with respect to the DC endocytic machinery, showing the importance of cytosolic translocation from acidifying endocytic structures. The review relates the DC endocytic pathways to immune response induction, and the potential advantages for these self-replicating RNA vaccines in the near future.

STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma membrane, ER, and ERC

DEFF Research Database (Denmark)

Garbarino, J.; Pan, M. H.; Chin, H. F.

2012-01-01

small hairpin RNA knockdown technology to reduce STARD4 expression in HepG2 cells. In a cholesterol-poor environment, we found that a reduction in STARD4 expression leads to retention of cholesterol at the plasma membrane, reduction of endoplasmic reticulum-associated cholesterol, and decreased ACAT...... synthesized cholesteryl esters. Furthermore, D4 KD cells exhibited a reduced rate of sterol transport to the endocytic recycling compartment after cholesterol repletion. Although these cells displayed normal endocytic trafficking in cholesterol-poor and replete conditions, cell surface low density lipoprotein...... membrane and the endocytic recycling compartment to the endoplasmic reticulum and perhaps other intracellular compartments as well. -Garbarino, J., M. Pan, H.F. Chin, F.W. Lund, F.R. Maxfield, and J.L. Breslow. STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma...

Unique Case Reports Associated with Ovarian Failure: Necessity of Two Intact X Chromosomes

Directory of Open Access Journals (Sweden)

Lakshmi Rao Kandukuri

2012-01-01

Full Text Available Premature ovarian failure is defined as the loss of functional follicles below the age of 40 years and the incidence of this abnormality is 0.1% among the 30–40 years age group. Unexplained POF is clinically recognized as amenorrhoea (>6 months with low level of oestrogen and raised level of Luteinizing Hormone (LH and Follicle Stimulating Hormone (FSH > 20 IU/l occurring before the age of 40. It has been studied earlier that chromosomal defects can impair ovarian development and its function. Since there is paucity of data on chromosomal defects in Indian women, an attempt is made to carry out cytogenetic evaluation in patients with ovarian failure. Cytogenetic analysis of women with ovarian defects revealed the chromosome abnormalities to be associated with 14% of the cases analyzed. Interestingly, majority of the abnormalities involved the X-chromosome and we report two unique abnormalities, (46,XXdel(Xq21-22 and q28 and (mos,45XO/46,X+ringX involving X chromosome in association with ovarian failure. This study revealed novel X chromosome abnormalities associated with ovarian defects and these observations would be helpful in genetic counseling and apart from, infertility clinics using the information to decide suitable strategies to help such patients.

Comparative analyses identified species-specific functional roles in oral microbial genomes

Science.gov (United States)

Chen, Tsute; Gajare, Prasad; Olsen, Ingar; Dewhirst, Floyd E.

2017-01-01

ABSTRACT The advent of next generation sequencing is producing more genomic sequences for various strains of many human oral microbial species and allows for insightful functional comparisons at both intra- and inter-species levels. This study performed in-silico functional comparisons for currently available genomic sequences of major species associated with periodontitis including Aggregatibacter actinomycetemcomitans (AA), Porphyromonas gingivalis (PG), Treponema denticola (TD), and Tannerella forsythia (TF), as well as several cariogenic and commensal streptococcal species. Complete or draft sequences were annotated with the RAST to infer structured functional subsystems for each genome. The subsystems profiles were clustered to groups of functions with similar patterns. Functional enrichment and depletion were evaluated based on hypergeometric distribution to identify subsystems that are unique or missing between two groups of genomes. Unique or missing metabolic pathways and biological functions were identified in different species. For example, components involved in flagellar motility were found only in the motile species TD, as expected, with few exceptions scattered in several streptococcal species, likely associated with chemotaxis. Transposable elements were only found in the two Bacteroidales species PG and TF, and half of the AA genomes. Genes involved in CRISPR were prevalent in most oral species. Furthermore, prophage related subsystems were also commonly found in most species except for PG and Streptococcus mutans, in which very few genomes contain prophage components. Comparisons between pathogenic (P) and nonpathogenic (NP) genomes also identified genes potentially important for virulence. Two such comparisons were performed between AA (P) and several A. aphrophilus (NP) strains, and between S. mutans + S. sobrinus (P) and other oral streptococcal species (NP). This comparative genomics approach can be readily used to identify functions unique to

Fuzzy Analogues of Sets and Functions Can Be Uniquely Determined from the Corresponding Ordered Category: A Theorem

Directory of Open Access Journals (Sweden)

Christian Servin

2018-01-01

Full Text Available In modern mathematics, many concepts and ideas are described in terms of category theory. From this viewpoint, it is desirable to analyze what can be determined if, instead of the basic category of sets, we consider a similar category of fuzzy sets. In this paper, we describe a natural fuzzy analog of the category of sets and functions, and we show that, in this category, fuzzy relations (a natural fuzzy analogue of functions can be determined in category terms—of course, modulo 1-1 mapping of the corresponding universe of discourse and 1-1 re-scaling of fuzzy degrees.

Classical Solutions of Path-Dependent PDEs and Functional Forward-Backward Stochastic Systems

Directory of Open Access Journals (Sweden)

Shaolin Ji

2013-01-01

Full Text Available In this paper we study the relationship between functional forward-backward stochastic systems and path-dependent PDEs. In the framework of functional Itô calculus, we introduce a path-dependent PDE and prove that its solution is uniquely determined by a functional forward-backward stochastic system.

[Reactance proneness, collectivism, uniqueness, and resistance to persuasion].

Science.gov (United States)

Imajo, Shuzo

2002-10-01

This study examined the reliability and validity of Japanese psychological reactance scales. A total of 167 undergraduates completed a questionnaire of Therapeutic Reactance Scale (TRS), the Hong Reactance Scale (HRS), the Uniqueness Scale, and the Collectivism Scale. They also received messages involving three persuasion situations that were either high or low in terms of threat, and were asked to describe their reactions to them. The author categorized the reactions into three: acceptance, indirect resistance, and direct resistance. Reliabilities of the reactance scales were satisfactory. Their scores positively correlated with uniqueness scores, and negatively with collectivism scores. Those high on reactance proneness were less persuaded in two of the three situations. But in the third, an HRS by threat interaction was observed, indicating that only those who were high on reactance proneness under the high-threat condition showed resistance to persuasion. These results suggest that the Japanese versions of reactance scale were reliable and valid. However, the assertiveness aspect of TRS may not be appropriate for the definition of reactance. The influence of culture on psychological reactance was also discussed.

Uniqueness of human running coordination: The integration of modern and ancient evolutionary innovations

Directory of Open Access Journals (Sweden)

John eKiely

2016-04-01

Full Text Available Running is a pervasive activity across human cultures and a cornerstone of contemporary health, fitness and sporting activities. Yet for the overwhelming predominance of human existence running was an essential prerequisite for survival. A means to hunt, and a means to escape when hunted. In a very real sense humans have evolved to run. Yet curiously, perhaps due to running’s cultural ubiquity and the natural ease with which we learn to run, we rarely consider the uniqueness of human bipedal running within the animal kingdom. Our unique upright, single stance, bouncing running gait imposes a unique set of coordinative difficulties. Challenges demanding we precariously balance our fragile brains in the very position where they are most vulnerable to falling injury while simultaneously retaining stability, steering direction of travel, and powering the upcoming stride: all within the abbreviated time-frames afforded by short, violent ground contacts separated by long flight times. These running coordination challenges are solved through the tightly-integrated blending of primitive evolutionary legacies, conserved from reptilian and vertebrate lineages, and comparatively modern, more exclusively human, innovations. The integrated unification of these top-down and bottom-up control processes bestows humans with an agile control system, enabling us to readily modulate speeds, change direction, negotiate varied terrains and to instantaneously adapt to changing surface conditions. The seamless integration of these evolutionary processes is facilitated by pervasive, neural and biological, activity-dependent adaptive plasticity. Over time, and with progressive exposure, this adaptive plasticity shapes neural and biological structures to best cope with regularly imposed movement challenges. This pervasive plasticity enables the gradual construction of a robust system of distributed coordinated control, comprised of processes that are so deeply

Unique solvability of some two-point boundary value problems for linear functional differential equations with singularities

Czech Academy of Sciences Publication Activity Database

Rontó, András; Samoilenko, A. M.

2007-01-01

Roč. 41, - (2007), s. 115-136 ISSN 1512-0015 R&D Projects: GA ČR(CZ) GA201/06/0254 Institutional research plan: CEZ:AV0Z10190503 Keywords : two-point problem * functional differential equation * singular boundary problem Subject RIV: BA - General Mathematics

Unique identification code for medical fundus images using blood vessel pattern for tele-ophthalmology applications.

Science.gov (United States)

Singh, Anushikha; Dutta, Malay Kishore; Sharma, Dilip Kumar

2016-10-01

Identification of fundus images during transmission and storage in database for tele-ophthalmology applications is an important issue in modern era. The proposed work presents a novel accurate method for generation of unique identification code for identification of fundus images for tele-ophthalmology applications and storage in databases. Unlike existing methods of steganography and watermarking, this method does not tamper the medical image as nothing is embedded in this approach and there is no loss of medical information. Strategic combination of unique blood vessel pattern and patient ID is considered for generation of unique identification code for the digital fundus images. Segmented blood vessel pattern near the optic disc is strategically combined with patient ID for generation of a unique identification code for the image. The proposed method of medical image identification is tested on the publically available DRIVE and MESSIDOR database of fundus image and results are encouraging. Experimental results indicate the uniqueness of identification code and lossless recovery of patient identity from unique identification code for integrity verification of fundus images. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Left ventricular functional, structural and energetic effects of normal aging: Comparison with hypertension.

Directory of Open Access Journals (Sweden)

Jehill D Parikh

Full Text Available Both aging and hypertension are significant risk factors for heart failure in the elderly. The purpose of this study was to determine how aging, with and without hypertension, affects left ventricular function.Cross-sectional study of magnetic resonance imaging and 31P spectroscopy-based measurements of left ventricular structure, global function, strains, pulse wave velocity, high energy phosphate metabolism in 48 normal subjects and 40 treated hypertensive patients (though no other cardiovascular disease or diabetes stratified into 3 age deciles from 50-79 years.Normal aging was associated with significant increases in systolic blood pressure, vascular stiffness, torsion, and impaired diastolic function (all P<0.05. Age-matched hypertension exacerbated the effects of aging on systolic pressure, and diastolic function. Hypertension alone, and not aging, was associated with increased left ventricular mass index, reduced energetic reserve, reduced longitudinal shortening and increased endocardial circumferential shortening (all P<0.05. Multiple linear regression analysis showed that these unique hypertensive features were significantly related to systolic blood pressure (P<0.05.1 Hypertension adds to the age-related changes in systolic blood pressure and diastolic function; 2 hypertension is uniquely associated with changes in several aspects of left ventricular structure, function, systolic strains, and energetics; and 3 these uniquely hypertensive-associated parameters are related to the level of systolic blood pressure and so are potentially modifiable.

Comparing Unique Title Coverage of Web of Science and Scopus in Earth and Atmospheric Sciences

Science.gov (United States)

Barnett, Philip; Lascar, Claudia

2012-01-01

The current journal titles in earth and atmospheric sciences, that are unique to each of two databases, Web of Science and Scopus, were identified using different methods. Comparing by subject category shows that Scopus has hundreds of unique titles, and Web of Science just 16. The titles unique to each database have low SCImago Journal Rank…

Somatic cell nuclear transfer: Infinite reproduction of a unique diploid genome

International Nuclear Information System (INIS)

Kishigami, Satoshi; Wakayama, Sayaka; Hosoi, Yoshihiko; Iritani, Akira; Wakayama, Teruhiko

2008-01-01

In mammals, a diploid genome of an individual following fertilization of an egg and a spermatozoon is unique and irreproducible. This implies that the generated unique diploid genome is doomed with the individual ending. Even as cultured cells from the individual, they cannot normally proliferate in perpetuity because of the 'Hayflick limit'. However, Dolly, the sheep cloned from an adult mammary gland cell, changes this scenario. Somatic cell nuclear transfer (SCNT) enables us to produce offspring without germ cells, that is, to 'passage' a unique diploid genome. Animal cloning has also proven to be a powerful research tool for reprogramming in many mammals, notably mouse and cow. The mechanism underlying reprogramming, however, remains largely unknown and, animal cloning has been inefficient as a result. More momentously, in addition to abortion and fetal mortality, some cloned animals display possible premature aging phenotypes including early death and short telomere lengths. Under these inauspicious conditions, is it really possible for SCNT to preserve a diploid genome? Delightfully, in mouse and recently in primate, using SCNT we can produce nuclear transfer ES cells (ntES) more efficiently, which can preserve the eternal lifespan for the 'passage' of a unique diploid genome. Further, new somatic cloning technique using histone-deacetylase inhibitors has been developed which can significantly increase the previous cloning rates two to six times. Here, we introduce SCNT and its value as a preservation tool for a diploid genome while reviewing aging of cloned animals on cellular and individual levels

Somatic cell nuclear transfer: infinite reproduction of a unique diploid genome.

Science.gov (United States)

Kishigami, Satoshi; Wakayama, Sayaka; Hosoi, Yoshihiko; Iritani, Akira; Wakayama, Teruhiko

2008-06-10

In mammals, a diploid genome of an individual following fertilization of an egg and a spermatozoon is unique and irreproducible. This implies that the generated unique diploid genome is doomed with the individual ending. Even as cultured cells from the individual, they cannot normally proliferate in perpetuity because of the "Hayflick limit". However, Dolly, the sheep cloned from an adult mammary gland cell, changes this scenario. Somatic cell nuclear transfer (SCNT) enables us to produce offspring without germ cells, that is, to "passage" a unique diploid genome. Animal cloning has also proven to be a powerful research tool for reprogramming in many mammals, notably mouse and cow. The mechanism underlying reprogramming, however, remains largely unknown and, animal cloning has been inefficient as a result. More momentously, in addition to abortion and fetal mortality, some cloned animals display possible premature aging phenotypes including early death and short telomere lengths. Under these inauspicious conditions, is it really possible for SCNT to preserve a diploid genome? Delightfully, in mouse and recently in primate, using SCNT we can produce nuclear transfer ES cells (ntES) more efficiently, which can preserve the eternal lifespan for the "passage" of a unique diploid genome. Further, new somatic cloning technique using histone-deacetylase inhibitors has been developed which can significantly increase the previous cloning rates two to six times. Here, we introduce SCNT and its value as a preservation tool for a diploid genome while reviewing aging of cloned animals on cellular and individual levels.

Loss of uniqueness in poro-mechanical model with enhanced media

International Nuclear Information System (INIS)

Sieffert, Y.; Marinelli, F.; Chambon, R.

2010-01-01

Document available in extended abstract form only. These paper deals with the problem of uniqueness in simulation the behavior of geo-materials with enhanced media to controlled the widths of bands. In the last 10 years, the loss of uniqueness has been clearly demonstrated in some initial boundary value problems involving constitutive equations modeling the degradation of the strength of materials. First in theoretical aspect with a simple test for a one dimensional problem of traction in a bar where the analytical solutions can be developed. In this article, It was also demonstrated that it is possible to retrieve all the analytical solutions in numerical simulations, only by using different starting guesses in the Newton's method. Then thanks to some classical numerical and experimental tests in geomechanical the non uniqueness is proved: the biaxial test and the borehole problem. However in all theses study, the geo-material is assumed to be monophasic. That's why is relevant to investigated the problem of uniqueness in taken into account the fluid part in the media. We deals in the framework of poro-mechanical model where the mechanical part is obeying a second gradient theory (not local) to ensure a regularization of the localisation pattern. This work is realized within the framework of the European Project TIMODAZ (Thermal Impact on the Damaged Zone Around a Radioactive Waste Disposal in Clay Host Rocks, http:// www.timodaz.eu/). As one benchmark in this project, the classical mechanical part is a Druecker-Prager model with a softening in the cohesion and a hardening in the frictional angle. It is a non-associated plasticity model for limited dilatancy. The parameters of this model are the same of this benchmark to simulated the Boom Clay material. Finally this paper demonstrates that several numerical solutions could be obtained as monophasic for the biaxial test modelling. (authors)

An Association of Unique microRNA Turnover Machinery with Prostate Cancer Progression

Science.gov (United States)

2017-10-01

targeting of critical androgen receptor -604 coregulator interactions in prostate cancer . Nature communications 4, 1923, 605 doi:10.1038/ncomms2912 (2013...AWARD NUMBER: W81XWH-16-1-0474 TITLE: An Association of Unique microRNA Turnover Machinery with Prostate Cancer Progression PRINCIPAL INVESTIGATOR...14 Sep 2017 4. Title An Association of Unique microRNA Turnover Machinery with Prostate Cancer Progression 5a. CONTRACT NUMBER 5b. GRANT NUMBER

Unmanned Aerial Vehicles unique cost estimating requirements

Science.gov (United States)

Malone, P.; Apgar, H.; Stukes, S.; Sterk, S.

Unmanned Aerial Vehicles (UAVs), also referred to as drones, are aerial platforms that fly without a human pilot onboard. UAVs are controlled autonomously by a computer in the vehicle or under the remote control of a pilot stationed at a fixed ground location. There are a wide variety of drone shapes, sizes, configurations, complexities, and characteristics. Use of these devices by the Department of Defense (DoD), NASA, civil and commercial organizations continues to grow. UAVs are commonly used for intelligence, surveillance, reconnaissance (ISR). They are also use for combat operations, and civil applications, such as firefighting, non-military security work, surveillance of infrastructure (e.g. pipelines, power lines and country borders). UAVs are often preferred for missions that require sustained persistence (over 4 hours in duration), or are “ too dangerous, dull or dirty” for manned aircraft. Moreover, they can offer significant acquisition and operations cost savings over traditional manned aircraft. Because of these unique characteristics and missions, UAV estimates require some unique estimating methods. This paper describes a framework for estimating UAV systems total ownership cost including hardware components, software design, and operations. The challenge of collecting data, testing the sensitivities of cost drivers, and creating cost estimating relationships (CERs) for each key work breakdown structure (WBS) element is discussed. The autonomous operation of UAVs is especially challenging from a software perspective.

Unique Features of Mobile Commerce

Institute of Scientific and Technical Information of China (English)

DING Xiaojun; IIJIMA Junichi; HO Sho

2004-01-01

While the market potentials and impacts of web-based e-commerce are still in the ascendant, the advances in wireless technologies and mobile networks have brought about a new business opportunity and research attention, what is termed mobile commerce. Commonly, mobile commerce is considered to be another new application of existing web-based e-commerce onto wireless networks, but as an independent business area, mobile commerce has its own advantages and challenges as opposed to traditional e-commerce applications. This paper focuses on exploring the unique features of mobile commerce as. Compared with traditional e-commerce. Also, there are still some limitations arisen in m-commerce in contrast to web-based e-commerce. Finally, current state of mobile commerce in Japan is presented in brief, with an introduction of several cases involving mobile commerce applications in today 's marketplace.

The Uniqueness of Islamic Culture

Directory of Open Access Journals (Sweden)

Sinan YILMAZ

2014-12-01

Full Text Available Abstract This paper examines the main reasons behind why Islamic culture is different than other cultures. In the introduction part of the paper, the usage area of the words culture and civilization were tackled. In the first part of the paper, an evaluation of the uniqueness of Islamic culture was made and examples about this were given. In the second part of the paper, evaluations about how Islamic culture has struggled with modernization and secularization and how it has shaped itself as a result of this were made. In the third part of the paper, the situation in which Islamic civilization has regressed against the Western civilization causing emerging arguments and the current situation in Islamic civilization have been addressed by making evaluations on culture and civilization. In the final part, evaluations on thesis this paper has used were made.

Regional cluster policy between best practices and cultural uniqueness

NARCIS (Netherlands)

Hospers, Gerrit J.; Beugelsdijk, S.; Boneschansker, E.; van Dijk, J.; Jansma, L.G.J.; Verhaar, K.H.A.

2004-01-01

This chapter deals with an intriguing paradox in current regional economic policy: whereas unique local factors are increasingly seen as the determinants of regional economic success, more and more governments simultaneously try to copy policy experiences that have proved successful in a particular

A unique structure for the multiplexer in quantum-dot cellular automata to create a revolution in design of nanostructures

Energy Technology Data Exchange (ETDEWEB)

Naji Asfestani, Mazaher; Rasouli Heikalabad, Saeed, E-mail: s.rasouli@iaut.ac.ir

2017-05-01

Quantum-dot cellular automata (QCA) is the advent of technology and suitable replacement for semiconductor transistor technology. In this paper, a unique structure for the 2:1 multiplexer is presented in QCA. The structure of this component is simple, ultra-efficient and very useful to implement the various logical functions. The proposed structure does not follow any Boolean function. It takes advantage of the inherent characteristics of quantum technology to produce the desired output. Based on these principles, we design the new and efficient structures for the 4:1 multiplexer and 8:1 multiplexer in the QCA technology. These structures are designed with QCADesigner simulator and simulation results are examined. Investigation results indicate the amazing performance of proposed structure compared to existing structures in terms of area, complexity, power consumption and latency.

Ontogeny and function of murine epidermal Langerhans cells.

Science.gov (United States)

Kaplan, Daniel H

2017-09-19

Langerhans cells (LCs) are epidermis-resident antigen-presenting cells that share a common ontogeny with macrophages but function as dendritic cells (DCs). Their development, recruitment and retention in the epidermis is orchestrated by interactions with keratinocytes through multiple mechanisms. LC and dermal DC subsets often show functional redundancy, but LCs are required for specific types of adaptive immune responses when antigen is concentrated in the epidermis. This Review will focus on those developmental and functional properties that are unique to LCs.

Unique Migraine Subtypes, Rare Headache Disorders, and Other Disturbances.

Science.gov (United States)

Goadsby, Peter J

2015-08-01

The medical aphorism that common things happen commonly makes unique (and less common) migraine subtypes especially appropriate to review for the general neurologist. This article also identifies some rare headache disorders and other disturbances, and offers strategies to manage them. This article discusses migraine with brainstem aura, which is troublesome clinically and has had a change in terminology in the International Classification of Headache Disorders, Third Edition, beta version (ICHD-3 beta), and hemiplegic migraine, which is also troublesome in practice. The rare headache disorder hypnic headache and the exploding head syndrome are also discussed. When hypnic headache is recognized, it is eminently treatable, while exploding head syndrome is a benign condition with no reported consequences. Unique migraine subtypes, rare headache disorders, and other disturbances present to neurologists. When recognized, they can often be managed very well, which offers significant benefits to patients and practice satisfaction to neurologists.