cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Regulation of the Transcriptional Activity of the IRF7 Promoter by a Pathway Independent of Interferon Signaling
Creators: name: Ning, Shunbin
name: Pagano, Joseph S.
name: Huye, Leslie E.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2005

description: Genes containing an interferon (IFN)-stimulated response element (ISRE) can be divided into two groups according to their inducibility by IFN and virus infection: one induced only by IFN and the other induced by both IFN and virus infection. Although it is now clear that IFN regulatory factor 7 (IRF7) is a multifunctional gene essential for induction of type I IFNs, regulation of the IRF7 promoter (IRF7p) is poorly understood. The IRF7 gene includes two IFN responsive elements, an IRF-binding element (IRFE) in the promoter region and an ISRE in the first intron, and is induced by the IFN-triggered Jak-STAT pathway by binding of the IFN-stimulated gene factor 3 (ISGF3) complex to the ISRE. In this study, we demonstrate that IRF3 and IRF7, which with the coactivators CREB-binding protein and P300 form the virus-activated factor (VAF) complex upon Sendai virus infection, bind to the IRF7 ISRE and IRFE and can directly activate IRF7 transcription. Promoter reporter assays show that both the ISRE and IRFE are responsive to activation by IRF7 and IRF3. In cells transiently expressing IRF7 or/and IRF3, the VAF level and binding of VAF are clearly increased after Sendai virus infection. Studies with Jak1 kinase inactive 293 cells that were stably transfected with a Jak1 kinase dead dominant negative construct, and the mutant cell lines SAN (IFNalpha-/beta-), U2A (IRF9-), U4A (Jak1-), and DKO (IRF1-/IRF2-) show that the IRF7 transcription activated directly by VAF is distinct from and independent of the IFN signaling pathway. Thus, IRF7 transcription is autoregulated by binding of the IRF7-containing VAF to its own ISRE and IRFE. The results show two distinct mechanisms for the activation of the IRF7 promoter, by IFN and by virus infection. A regulatory network between type I IFNs and IRF7 is proposed. The distinct pathways may reflect special roles for an efficient antiviral response at different stages of virus infection.
Le escursioni geologiche della Scuola Alpina di Morbegno: il fondovalle della Valtellina
Creators: name: Cameron, Enrico
Publisher: name: Zenodo
Year: 2025
Subjects: Geologia
Geomorfologia
Outdoor education
Scuola Alpina

description: Morbegno è il principale centro urbano della Bassa Valtellina ed è sede dell’Istituto Comprensivo 2 Damiani, che nel 2017 ha aderito al progetto Interreg Alpine Space – YOUrALPS, finalizzato a sviluppare un nuovo modello di scuola centrato sui processi ambientali e socioeconomici delle Alpi. Nel 2020 la scuola secondaria di primo grado dell’Istituto ha ottenuto la certificazione europea di Scuola Alpina, creando un vero e proprio indirizzo. L’obiettivo principale è riavvicinare gli studenti al proprio territorio, sensibilizzandoli verso le caratteristiche, le risorse e le opportunità dell’ambiente montano. Il testo descrive un'escursione a tema geologico e geomorfologico organizzata dalla Scuola Alpina, che riguarda l’osservazione di importanti fenomeni franosi, e dei loro effetti, lungo un itinerario che si snoda sul fondovalle della Valtellina. Una versione sintetica del testo è stata pubblicata su Geologicamente, magazine di attualità e cultura delle geoscienze della Società Geologica Italiana (n. 16, marzo 2025).
RGS12 Interacts with the SNARE-binding Region of the Ca v 2.2 Calcium Channel
Creators: name: Hains, Melinda D.
name: Diversé-Pierluissi, María
name: Strock, Jesse
name: Lau, King Kei
name: Siderovski, David P.
name: Cabanilla, Nory Jun
name: Richman, Ryan W.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2005

description: Activation of GABAB receptors in chick dorsal root ganglion (DRG) neurons inhibits the Cav2.2 calcium channel in both a voltage-dependent and voltage-independent manner. The voltage-independent inhibition requires activation of a tyrosine kinase that phosphorylates the alpha1 subunit of the channel and thereby recruits RGS12, a member of the "regulator of G protein signaling" (RGS) proteins. Here we report that RGS12 binds to the SNARE-binding or "synprint" region (amino acids 726-985) in loop II-III of the calcium channel alpha1 subunit. A recombinant protein encompassing the N-terminal PTB domain of RGS12 binds to the synprint region in protein overlay and surface plasmon resonance binding assays; this interaction is dependent on tyrosine phosphorylation and yet is within a sequence that differs from the canonical NPXY motif targeted by other PTB domains. In electrophysiological experiments, microinjection of DRG neurons with synprint-derived peptides containing the tyrosine residue Tyr-804 altered the rate of desensitization of neurotransmitter-mediated inhibition of the Cav2.2 calcium channel, whereas peptides centered about a second tyrosine residue, Tyr-815, were without effect. RGS12 from a DRG neuron lysate was precipitated using synprint peptides containing phosphorylated Tyr-804. The high degree of conservation of Tyr-804 in the SNARE-binding region of Cav2.1 and Cav2.2 calcium channels suggests that this region, in addition to the binding of SNARE proteins, is also important for determining the time course of the modulation of calcium current via tyrosine phosphorylation.
Ryanodine Receptors in Muscarinic Receptor-mediated Bronchoconstriction
Creators: name: Rosenberg, Paul B.
name: Eu, Jerry P.
name: Stiber, Jonathan A.
name: Du, Wanglei
name: Meissner, Gerhard
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2005

description: Ryanodine receptors (RyRs), intracellular calcium release channels essential for skeletal and cardiac muscle contraction, are also expressed in various types of smooth muscle cells. In particular, recent studies have suggested that in airway smooth muscle cells (ASMCs) provoked by spasmogens, stored calcium release by the cardiac isoform of RyR (RyR2) contributes to the calcium response that leads to airway constriction (bronchoconstriction). Here we report that mouse ASMCs also express the skeletal muscle and brain isoforms of RyRs (RyR1 and RyR3, respectively). In these cells, RyR1 is localized to the periphery near the cell membrane, whereas RyR3 is more centrally localized. Moreover, RyR1 and/or RyR3 in mouse airway smooth muscle also appear to mediate bronchoconstriction caused by the muscarinic receptor agonist carbachol. Inhibiting all RyR isoforms with > or = 200 microM ryanodine attenuated the graded carbachol-induced contractile responses of mouse bronchial rings and calcium responses of ASMCs throughout the range of carbachol used (50 nM to > or = 3 microM). In contrast, inhibiting only RyR1 and RyR3 with 25 microM dantrolene attenuated these responses caused by high (>500 nM) but not by low concentrations of carbachol. These data suggest that, as the stimulation of muscarinic receptor in the airway smooth muscle increases, RyR1 and/or RyR3 also mediate the calcium response and thus bronchoconstriction. Our findings provide new insights into the complex calcium signaling in ASMCs and suggest that RyRs are potential therapeutic targets in bronchospastic disorders such as asthma.
SMAD and p38 MAPK Signaling Pathways Independently Regulate α1(I) Collagen Gene Expression in Unstimulated and Transforming Growth Factor-β-stimulated Hepatic Stellate Cells
Creators: name: Westwick, John K.
name: Sato, Nobuhiro
name: Rippe, Richard A.
name: Ikejima, Kenichi
name: Tsukada, Shigeki
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2005

description: The hepatic stellate cell (HSC) is the predominant cell type responsible for excess collagen deposition during liver fibrosis. Both transforming growth factor-beta (TGF-beta), the most potent fibrogenic cytokine for HSCs, which classically activates Smad signaling, and p38 MAPK signaling have been shown to influence collagen gene expression; however, the relative contribution and mechanisms that these two signaling pathways have in regulating collagen gene expression have not been investigated. The aim of this study was to investigate the relative roles and mechanisms of both Smad and p38 MAPK signaling in alpha1(I) collagen gene expression in HSCs. Inhibiting either p38 MAPK or Smad signaling reduced alpha1(I) collagen mRNA expression in untreated or TGF-beta-treated HSCs, and when both signaling pathways were simultaneously inhibited, alpha1(I) collagen gene expression was essentially blocked. Both signaling pathways were found to independently and additively increase alpha1(I) collagen gene expression by transcriptional mechanisms. TGF-beta treatment increased alpha1(I) collagen mRNA half-life, mediated by increased stability of alpha1(I) collagen mRNA through p38 MAPK signaling but not through Smad signaling. In conclusion, both p38 MAPK and Smad signaling independently and additively regulate alpha1(I) collagen gene expression by transcriptional activation, whereas p38 MAPK and not Smad signaling increased alpha1(I) collagen mRNA stability.
Nexus and Dirac lines in topological materials
Creators: name: Heikkila, T. T.
name: Volovik, G. E.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Mesoscale and Nanoscale Physics (cond-mat.mes-hall)
subject: FOS: Physical sciences

description: We consider the $Z_2$ topology of the Dirac lines, i.e., lines of band contacts, on an example of graphite. Four lines --- three with topological charge $N_1=1$ each and one with $N_1=-1$ --- merge together near the H-point and annihilate due to summation law $1+1+1-1=0$. The merging point is similar to the real-space nexus, an analog of the Dirac monopole at which the $Z_2$ strings terminate.
description: 7 pages, 3 figures; some minor corrections, added references
title: Bi-directional grid constrained stochastic processes and their applications in mathematical finance
Creators: name: Taranto, Dr. Aldo
Publisher: name: University of Southern Queensland
Year: 2022
Subjects: classificationCode: 490510
subject: Stochastic analysis and modelling
valueUri: https://www.abs.gov.au/statistics/classifications/australian-and-new-zealand-standard-research-classification-anzsrc/latest-release
classificationCode: 490106
subject: Financial mathematics
valueUri: https://www.abs.gov.au/statistics/classifications/australian-and-new-zealand-standard-research-classification-anzsrc/latest-release
classificationCode: 490506
subject: Probability theory
valueUri: https://www.abs.gov.au/statistics/classifications/australian-and-new-zealand-standard-research-classification-anzsrc/latest-release

description: A statement of the research problem can be expressed, simply as, can bi-directional grid trading (BGT) be distilled into a mathematical model that can then be used to demonstrate that the corresponding grid trading problem (GTP) leads to ruin at a much slower rate than the well known gambler's ruin problem (GRP)? The methods and procedures utilized in this thesis examine various probability theory and stochastic process concepts and techniques, and apply them to mathematical finance, in particular to model the BGT strategies of algorithmic trading. My original contribution to knowledge is to take Ito diffusions and constrain them via various geometric schemes so as to keep them bounded within two (bi-directional) hidden barriers per distance dimension. I have called this novel research 'bi-directional grid constrained' (BGC) stochastic processes (BGCSPs). The BGCSP research is related to and compliments the Langevin, Ornstein-Ulhenbeck and multi-skew Brownian motion (M-SBM) stochastic differential equations (SDEs). A summary of findings includes the publishing of three research papers in applied probability theory for BGCSPs. The research also contributes to knowledge by implementing the theory into algorithms, which allow one to undertake extensive simulations which help visualise the resulting geometry. Armed with the insights of this theory, the GTP has been stated and modelled mathematically, allowing one to better simulate the stochastic dynamics of grid trading and its parallels with dynamic portfolio management and optimization. This has resulted in additional four published research papers in applied mathematical finance. The thesis concludes by examining a number of related areas that provide additional avenues for further research in this field.
Structural and Biochemical Characterization of CIB1 Delineates a New Family of EF-hand-containing Proteins
Creators: name: Ferrara, Joseph D.
name: Parise, Leslie V.
name: Yang, Cheng
name: Singer, Alex U.
name: Sondek, John
name: Betts, Laurie
name: Gentry, Holly R.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2005

description: CIB1 (CIB) is an EF-hand-containing protein that binds multiple effector proteins, including the platelet alphaIIbbeta3 integrin and several serine/threonine kinases and potentially modulates their function. The crystal structure for Ca(2+)-bound CIB1 has been determined at 2.0 A resolution and reveals a compact alpha-helical protein containing four EF-hands, the last two of which bind calcium ions in the standard fashion seen in many other EF-hand proteins. CIB1 shares high structural similarity with calcineurin B and the neuronal calcium sensor (NCS) family of EF-hand-containing proteins. Most importantly, like calcineurin B and NCS proteins, which possess a large hydrophobic pocket necessary for ligand binding, CIB1 contains a hydrophobic pocket that has been implicated in ligand binding by previous mutational analysis. However, unlike several NCS proteins, Ca(2+)-bound CIB1 is largely monomeric whether bound to a relevant peptide ligand or ligand-free. Differences in structure, oligomeric state, and phylogeny define a new family of CIB1-related proteins that extends from arthropods to humans.
Superoxide Anion Radical Modulates the Activity of Ras and Ras-related GTPases by a Radical-based Mechanism Similar to That of Nitric Oxide
Creators: name: Campbell, Sharon L.
name: Heo, Jongyun
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2005

description: Ras GTPases cycle between inactive GDP-bound and active GTP-bound states to modulate a diverse array of processes involved in cellular growth control. The activity of Ras is up-regulated by cellular agents, including both protein (guanine nucleotide exchange factors) and redox-active agents (nitric oxide (NO) and superoxide anion radical (O2*). We have recently elucidated the mechanism by which NO promotes guanine nucleotide dissociation of redox-active NKCD motif-containing Ras and Ras-related GTPases. In this study, we show that guanine nucleotide dissociation is enhanced upon exposure of the redox-active GTPases, Ras and Rap1A, to O2* and provide evidence for the efficient guanine nucleotide reassociation in the presence of the radical quenching agent ascorbate to complete guanine nucleotide exchange. In vivo, guanine nucleotide reassociation is necessary to populate Ras in its biologically active GTP-bound form after the dissociation of GDP. We further show that treatment of the redox-active GTPases with O2* releases GDP in form of an unstable the oxygenated GDP adduct, putatively assigned as 5-oxo-GDP. 5-Oxo-GDP was not produced from either the C118S or the F28L Ras variants upon the treatment of O2*, supporting the involvement of residues Cys118 and Phe28 in O2*-mediated Ras guanine nucleotide dissociation. These results indicate that the mechanism of O2*-mediated Ras guanine nucleotide dissociation is similar to that of NO/O2-mediated Ras guanine nucleotide dissociation.
The Chemical Composition of τ Ceti and Possible Effects on Terrestrial Planets
Creators: name: Pagano, Michael
name: Truitt, Amanda
name: Young, Patrick A.
name: Shim, Sang-Heon
Publisher: name: arXiv
Year: 2015
Subjects: subject: Earth and Planetary Astrophysics (astro-ph.EP)
subject: FOS: Physical sciences

description: τ Ceti (HD10700), a G8 dwarf with solar mass of 0.78, is a close (3.65 pc) sun-like star where 5 possibly terrestrial planet candidates (minimum masses of 2, 3.1, 3.5, 4.3, and 6.7 Earth masses) have recently been discovered. We report abundances of 23 elements using spectra from the MIKE spectrograph on Magellan. Using stellar models with the abundances determined here, we calculate the position of the classical habitable zone with time. At the current best fit age, 7.63 Gy, up to two planets (e and f) may be in the habitable zone, depending on atmospheric properties. The Mg/Si ratio of the star is found to be 1.78, which is much greater than for Earth (about 1.2). With a system that has such an excess of Mg to Si ratio it is possible that the mineralogical make-up of planets around τ Ceti could be significantly different from that of Earth, with possible oversaturation of MgO, resulting in an increase in the content of olivine and ferropericlase compared with Earth. The increase in MgO would have a drastic impact on the rheology of the mantles of the planets around τ Ceti.
description: 17 pages, 1 figure, supplemental table, Astrophysical Journal
The Apical Targeting Signal of the P2Y 2 Receptor Is Located in Its First Extracellular Loop
Creators: name: Wolff, Samuel C.
name: Qi, Ai Dong
name: Nicholas, Robert A.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2005

description: P2Y2 and P2Y4 receptors, which have 52% sequence identity, are both expressed at the apical membrane of Madin-Darby canine kidney cells, but the locations of their apical targeting signals are distinctly different. The targeting signal of the P2Y2 receptor is located between the N terminus and 7TM, whereas that of the P2Y4 receptor is present in its C-terminal tail. To identify the apical targeting signal in the P2Y2 receptor, regions of the P2Y2 receptor were progressively substituted with the corresponding regions of the P2Y4 receptor lacking its targeting signal. Characterization of these chimeras and subsequent mutational analysis revealed that four amino acids (Arg95, Gly96, Asp97, and Leu108) in the first extracellular loop play a major role in apical targeting of the P2Y2 receptor. Mutation of RGD to RGE had no effect on P2Y2 receptor targeting, indicating that receptor-integrin interactions are not involved in apical targeting. P2Y2 receptor mutants were localized in a similar manner in Caco-2 colon epithelial cells. This is the first identification of an extracellular protein-based targeting signal in a seven-transmembrane receptor.
The Co-chaperone Carboxyl Terminus of Hsp70-interacting Protein (CHIP) Mediates α-Synuclein Degradation Decisions between Proteasomal and Lysosomal Pathways
Creators: name: Shin, Youngah
name: McLean, Pamela J.
name: Hyman, Bradley T.
name: Klucken, Jochen
name: Patterson, Cam
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2005

description: Alpha-synuclein is a major component of Lewy bodies, the pathological hallmark of Parkinson disease, dementia with Lewy bodies, and related disorders. Misfolding and aggregation of alpha-synuclein is thought to be a critical cofactor in the pathogenesis of certain neurodegenerative diseases. In the current study, we investigate the role of the carboxyl terminus of Hsp70-interacting protein (CHIP) in alpha-synuclein aggregation. We demonstrate that CHIP is a component of Lewy bodies in the human brain, where it colocalizes with alpha-synuclein and Hsp70. In a cell culture model, endogenous CHIP colocalizes with alpha-synuclein and Hsp70 in intracellular inclusions, and overexpression of CHIP inhibits alpha-synuclein inclusion formation and reduces alpha-synuclein protein levels. We demonstrate that CHIP can mediate alpha-synuclein degradation by two discrete mechanisms that can be dissected using deletion mutants; the tetratricopeptide repeat domain is critical for proteasomal degradation, whereas the U-box domain is sufficient to direct alpha-synuclein toward the lysosomal degradation pathway. Furthermore, alpha-synuclein, synphilin-1, and Hsp70 all coimmunoprecipitate with CHIP, raising the possibility of a direct alpha-synuclein-CHIP interaction. The fact that the tetratricopeptide repeat domain is required for the effects of CHIP on alpha-synuclein inclusion morphology, number of inclusions, and proteasomal degradation as well as the direct interaction of CHIP with Hsp70 implicates a cooperation of CHIP and Hsp70 in these processes. Taken together, these data suggest that CHIP acts a molecular switch between proteasomal and lysosomal degradation pathways.
Figure S6b from Expansion in geographical and morphological space drives continued lineage diversification in a global passerine radiation
Creators: name: Kennedy, Jonathan D.
name: Borregaard, Michael K.
name: Marki, Petter Z.
name: Machac, Antonin
name: Fjeldså, Jon
name: Rahbek, Carsten
Publisher: name: The Royal Society
Year: 2018
Subjects: subject: Evolutionary Biology
subject: FOS: Biological sciences
subject: Ecology

description: Why diversification rates vary so extensively across the tree of life remains an important yet unresolved issue in biology. Two prominent and potentially independent factors proposed to explain these trends reflect the capacity of lineages to expand into new areas of (i) geographical or (ii) ecological space. Here, we present the first global assessment of how diversification rates vary as a consequence of geographical and ecological expansion, studying these trends among 15 speciose passerine families (together approximately 750 species) using phylogenetic path analysis. We find that relative slowdowns in diversification rates characterize families that have accumulated large numbers of co-occurring species (at the 1° scale) within restricted geographical areas. Conversely, more constant diversification through time is prevalent among families in which species show limited range overlap. Relative co-occurrence is itself also a strong predictor of ecological divergence (here approximated by morphological divergence among species); however, once the relationship between co-occurrence and diversification rates have been accounted for, increased ecological divergence is an additional explanatory factor accounting for why some lineages continue to diversify towards the present. We conclude that opportunities for prolonged diversification are predominantly determined by continued geographical range expansion and to a lesser degree by ecological divergence among lineages.
Transport in indium-decorated graphene
Creators: name: Chandni, U.
name: Henriksen, Erik A.
name: Eisenstein, J. P.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Mesoscale and Nanoscale Physics (cond-mat.mes-hall)
subject: FOS: Physical sciences

description: The electronic transport properties of single layer graphene having a dilute coating of indium adatoms has been investigated. Our studies establish that isolated indium atoms donate electrons to graphene and become a source of charged impurity scattering, affecting the conductivity as well as magnetotransport properties of the pristine graphene. Notably, a positive magnetoresistance is observed over a wide density range after In doping. The low field magnetoresistance carries signatures of quantum interference effects which are significantly altered by the adatoms.
description: 8 pages, 6 figures
(1618) Henry Solly
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
Figure S6a from Expansion in geographical and morphological space drives continued lineage diversification in a global passerine radiation.
Creators: name: Kennedy, Jonathan D.
name: Borregaard, Michael K.
name: Marki, Petter Z.
name: Machac, Antonin
name: Fjeldså, Jon
name: Rahbek, Carsten
Publisher: name: The Royal Society
Year: 2018
Subjects: subject: Evolutionary Biology
subject: FOS: Biological sciences
subject: Ecology

description: Why diversification rates vary so extensively across the tree of life remains an important yet unresolved issue in biology. Two prominent and potentially independent factors proposed to explain these trends reflect the capacity of lineages to expand into new areas of (i) geographical or (ii) ecological space. Here, we present the first global assessment of how diversification rates vary as a consequence of geographical and ecological expansion, studying these trends among 15 speciose passerine families (together approximately 750 species) using phylogenetic path analysis. We find that relative slowdowns in diversification rates characterize families that have accumulated large numbers of co-occurring species (at the 1° scale) within restricted geographical areas. Conversely, more constant diversification through time is prevalent among families in which species show limited range overlap. Relative co-occurrence is itself also a strong predictor of ecological divergence (here approximated by morphological divergence among species); however, once the relationship between co-occurrence and diversification rates have been accounted for, increased ecological divergence is an additional explanatory factor accounting for why some lineages continue to diversify towards the present. We conclude that opportunities for prolonged diversification are predominantly determined by continued geographical range expansion and to a lesser degree by ecological divergence among lineages.
The Cystic Fibrosis Transmembrane Conductance Regulator Is Regulated by a Direct Interaction with the Protein Phosphatase 2A
Creators: name: Thelin, William R.
name: Kesimer, Mehmet
name: Milgram, Sharon L.
name: Sheehan, John K.
name: Tarran, Robert
name: Kreda, Silvia M.
name: Grubb, Barbara R.
name: Stutts, M. Jackson
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2005

description: The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel expressed at the apical surface of epithelia. Although the regulation of CFTR by protein kinases is well documented, channel deactivation by phosphatases is not well understood. We find that the serine/threonine phosphatase PP2A can physically associate with the CFTR COOH terminus. PP2A is a heterotrimeric phosphatase composed of a catalytic subunit and two divergent regulatory subunits (A and B). The cellular localization and substrate specificity of PP2A is determined by the unique combination of A and B regulatory subunits, which can give rise to at least 75 different enzymes. By mass spectrometry, we identified the exact PP2A regulatory subunits associated with CFTR as Aalpha and B'epsilon and find that the B'epsilon subunit binds CFTR directly. PP2A subunits localize to the apical surface of airway epithelia and PP2A phosphatase activity co-purifies with CFTR in Calu-3 cells. In functional assays, inhibitors of PP2A block rundown of basal CFTR currents and increase channel activity in excised patches of airway epithelia and in intact mouse jejunum. Moreover, PP2A inhibition in well differentiated human bronchial epithelial cells results in a CFTR-dependent increase in the airway surface liquid. Our data demonstrate that PP2A is a relevant CFTR phosphatase in epithelial tissues. Our results may help reconcile differences in phosphatase-mediated channel regulation observed for different tissues and cells. Furthermore, PP2A may be a clinically relevant drug target for CF, which should be considered in future studies.
The Role of p70 S6K in Hepatic Stellate Cell Collagen Gene Expression and Cell Proliferation
Creators: name: Tsukada, Shigeki
name: Gäbele, Erwin
name: Schrum, Laura W.
name: Brenner, David A.
name: Bataller, Ramon
name: Yata, Yutaka
name: Morris, Terry
name: Rippe, Richard A.
name: Reif, Shimon
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2005

description: During fibrosis the hepatic stellate cell (HSC) undergoes a complex activation process characterized by increased proliferation and extracellular matrix deposition. The 70-kDa ribosomal S6 kinase (p70S6K) is activated by mitogens, growth factors, and hormones in a phosphatidylinositol 3-kinase-dependent manner. p70S6K regulates protein synthesis, proliferation, and cell cycle control. Because these processes are involved in HSC activation, we investigated the role of p70S6K in HSC proliferation, cell cycle control, and type I collagen expression. Platelet-derived growth factor (PDGF) stimulated p70S6K phosphorylation, which was blocked by LY294002, an inhibitor of phosphatidylinositol 3-kinase. Rapamycin blocked phosphorylation of p70S6K but had no affect on PDGF-induced Akt phosphorylation, positioning p70S6K downstream of Akt. Transforming growth factor-beta, which inhibits HSC proliferation, did not affect PDGF-induced p70S6K phosphorylation. Rapamycin treatment did not affect alpha1(I) collagen mRNA but reduced type I collagen protein secretion. Expression of smooth muscle alpha-actin was not affected by rapamycin treatment, indicating that HSC activation was not altered. Rapamycin inhibited serum-induced DNA synthesis approximately 2-fold. Moreover, rapamycin decreased expression of cyclins D1, D3, and E but not cyclin D2, Rb-Ser780, and Rb-Ser795. Together, p70S6K plays a crucial role in HSC proliferation, collagen expression, and cell cycle control, thus representing a potential therapeutic target for liver fibrosis.
Figure S6c from Expansion in geographical and morphological space drives continued lineage diversification in a global passerine radiation.
Creators: name: Kennedy, Jonathan D.
name: Borregaard, Michael K.
name: Marki, Petter Z.
name: Machac, Antonin
name: Fjeldså, Jon
name: Rahbek, Carsten
Publisher: name: The Royal Society
Year: 2018
Subjects: subject: Evolutionary Biology
subject: FOS: Biological sciences
subject: Ecology

description: Why diversification rates vary so extensively across the tree of life remains an important yet unresolved issue in biology. Two prominent and potentially independent factors proposed to explain these trends reflect the capacity of lineages to expand into new areas of (i) geographical or (ii) ecological space. Here, we present the first global assessment of how diversification rates vary as a consequence of geographical and ecological expansion, studying these trends among 15 speciose passerine families (together approximately 750 species) using phylogenetic path analysis. We find that relative slowdowns in diversification rates characterize families that have accumulated large numbers of co-occurring species (at the 1° scale) within restricted geographical areas. Conversely, more constant diversification through time is prevalent among families in which species show limited range overlap. Relative co-occurrence is itself also a strong predictor of ecological divergence (here approximated by morphological divergence among species); however, once the relationship between co-occurrence and diversification rates have been accounted for, increased ecological divergence is an additional explanatory factor accounting for why some lineages continue to diversify towards the present. We conclude that opportunities for prolonged diversification are predominantly determined by continued geographical range expansion and to a lesser degree by ecological divergence among lineages.
Local zeta regularization and the scalar Casimir effect IV. The case of a rectangular box
Creators: name: Fermi, Davide
name: Pizzocchero, Livio
Publisher: name: arXiv
Year: 2015
Subjects: subject: Mathematical Physics (math-ph)
subject: High Energy Physics - Theory (hep-th)
subject: Quantum Physics (quant-ph)
subject: FOS: Physical sciences
subject: 81T55, 83C47

description: Applying the general framework for local zeta regularization proposed in Part I of this series of papers, we compute the renormalized vacuum expectation value of several observables (in particular, of the stress-energy tensor and of the total energy) for a massless scalar field confined within a rectangular box of arbitrary dimension.
description: Some overlaps with our works arXiv:1104.4330, arXiv:1505.00711, arXiv:1505.01044, arXiv:1505.01651. These overlaps aim to make the present paper self-contained, and do not involve the main results. In comparison with version v3, reference [26] added
Figure S6a from Expansion in geographical and morphological space drives continued lineage diversification in a global passerine radiation
Creators: name: Kennedy, Jonathan D.
name: Borregaard, Michael K.
name: Marki, Petter Z.
name: Machac, Antonin
name: Fjeldså, Jon
name: Rahbek, Carsten
Publisher: name: The Royal Society
Year: 2018
Subjects: subject: Evolutionary Biology
subject: FOS: Biological sciences
subject: Ecology

description: Why diversification rates vary so extensively across the tree of life remains an important yet unresolved issue in biology. Two prominent and potentially independent factors proposed to explain these trends reflect the capacity of lineages to expand into new areas of (i) geographical or (ii) ecological space. Here, we present the first global assessment of how diversification rates vary as a consequence of geographical and ecological expansion, studying these trends among 15 speciose passerine families (together approximately 750 species) using phylogenetic path analysis. We find that relative slowdowns in diversification rates characterize families that have accumulated large numbers of co-occurring species (at the 1° scale) within restricted geographical areas. Conversely, more constant diversification through time is prevalent among families in which species show limited range overlap. Relative co-occurrence is itself also a strong predictor of ecological divergence (here approximated by morphological divergence among species); however, once the relationship between co-occurrence and diversification rates have been accounted for, increased ecological divergence is an additional explanatory factor accounting for why some lineages continue to diversify towards the present. We conclude that opportunities for prolonged diversification are predominantly determined by continued geographical range expansion and to a lesser degree by ecological divergence among lineages.
Photoionization analysis of chemo-dynamical dwarf galaxies simulations
Creators: name: Melekh, B.
name: Recchi, S.
name: Hensler, G.
name: Buhajenko, O.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Astrophysics of Galaxies (astro-ph.GA)
subject: FOS: Physical sciences

description: Photoionization modelling allows to follow the transport, the emergence, and the absorption of photons taking into account all important processes in nebular plasmas. Such modelling needs the spatial distribution of density, chemical abundances and temperature, that can be provided by chemo-dynamical simulations (ChDS) of dwarf galaxies. We perform multicomponent photoionization modelling (MPhM) of the ionized gas using 2-D ChDSs of dwarf galaxies. We calculate emissivity maps for important nebular emission lines. Their intensities are used to derive the chemical abundance of oxygen by the so-called Te- and R23-methods. Some disagreements are found between oxygen abundances calculated with these methods and the ones coming from the ChDSs. We investigate the fraction of ionizing radiation emitted in the star-forming region which is able to leak out the galaxy. The time- and direction-averaged escape fraction in our simulation is 0.35-0.4. Finally, we have calculated the total Halpha lumi- nosity of our model galaxy using Kennicutt's calibration to derive the star-formation rate. This value has been compared to the 'true' rate in the ChDSs. The Halpha-based star-formation rate agrees with the true one only at the beginning of the simulation. Minor deviations arise later on and are due in part to the production of high-energy photons in the warm-hot gas, in part to the leakage of energetic photons out of the galaxy. The effect of artificially introduced thin dense shells (with thicknesses smaller than the ChDSs spatial resolution) is investigated, as well.
description: 17 pages, 14 figures. Accepted for publication in Monthly Notices of the Royal Astronomical Society
(1613) Philip Henry Wicksteed
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
On the Lorentz-breaking theory with higher derivatives in spinor sector
Creators: name: Nascimento, J. R.
name: Petrov, A. Yu.
name: Reyes, C. Marat
Publisher: name: arXiv
Year: 2015
Subjects: subject: High Energy Physics - Theory (hep-th)
subject: FOS: Physical sciences

description: We consider the two-point function of the gauge field in Lorentz-breaking theories with higher-derivative extension of the Dirac Lagrangian. We show that the Carroll-Field-Jackiw term naturally arises in this theory as a quantum correction being perfectly finite and thus displaying no ambiguities. Also, the finiteness of this term at low energy limit and the absence of large Lorentz violating corrections allows to avoid the fine-tuning problem.
description: 14 pages, version accepted to PRD
The Type I Hsp40 Zinc Finger-like Region Is Required for Hsp70 to Capture Non-native Polypeptides from Ydj1
Creators: name: Cyr, Douglas M.
name: Caplan, Avrom J.
name: Fan, Chun Yang
name: Lee, Paul
name: Ren, Hong Yu
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2005

description: The cytosolic yeast Hsp40 Ydj1 contains a conserved zinc finger-like region (ZFLR), which has two zinc-binding domains (ZBD), that helps regulate and specify Hsp70 function. To investigate the mechanism for Ydj1 ZFLR action, ZBDI and ZBDII mutants were constructed and characterized. ZBDII mutants exhibited temperature-sensitive growth defects, but yeast tolerated mutation of ZBDI. However, ZBDI and ZBDII mutants were defective at facilitating androgen receptor (AR) folding. Defective AR folding was associated with the accumulation of complexes between AR and Ydj1 ZFLR mutants and a reduction in Hsp70.AR complex formation. Purified Ydj1 ZBDI and ZBDII mutants could bind non-native polypeptides but could not deliver luciferase to Hsp70 and were defective at luciferase refolding. Interestingly, the ability of Ydj1 to synergize with Hsp70 to suppress thermally induced protein aggregation was blocked by mutation of ZBDII, but not ZBDI. Hence, ZBDII is required for yeast to survive heat stress because it is essential for Ydj1 to cooperate with Hsp70 to suppress protein aggregation. On the other hand, protein folding is dependent upon the action of both ZBDI and ZBDII because each is required for Hsp70 to capture non-native polypeptides from Ydj1.
Neutralino Dark Matter and Other LHC Predictions from Quasi Yukawa Unification
Creators: name: Shafi, Qaisar
name: Tanyildizi, Sukru Hanif
name: Un, Cem Salih
Publisher: name: arXiv
Year: 2015
Subjects: subject: High Energy Physics - Phenomenology (hep-ph)
subject: FOS: Physical sciences

description: We explore the dark matter and LHC implications of t-b-tau quasi Yukawa unification in the framework of supersymmetric models based on the gauge symmetry G=SU(4)_{c}\times SU(2)_{L}\times SU(2)_{R}. The deviation from exact Yukawa unification is quantified by a dimensionless parameter C (|C| ~ 2 TeV, while the first two family squarks and sleptons are of order 4-5 TeV and 3 TeV respectively.
Imaging Microwave and DC Magnetic Fields in a Vapor-Cell Rb Atomic Clock
Creators: name: Affolderbach, Christoph
name: Du, Guan-Xiang
name: Bandi, Thejesh
name: Horsley, Andrew
name: Treutlein, Philipp
name: Mileti, Gaetano
Publisher: name: arXiv
Year: 2015
Subjects: subject: Atomic Physics (physics.atom-ph)
subject: FOS: Physical sciences

description: We report on the experimental measurement of the DC and microwave magnetic field distributions inside a recently-developed compact magnetron-type microwave cavity, mounted inside the physics package of a high-performance vapor-cell atomic frequency standard. Images of the microwave field distribution with sub-100 $μ$m lateral spatial resolution are obtained by pulsed optical-microwave Rabi measurements, using the Rb atoms inside the cell as field probes and detecting with a CCD camera. Asymmetries observed in the microwave field images can be attributed to the precise practical realization of the cavity and the Rb vapor cell. Similar spatially-resolved images of the DC magnetic field distribution are obtained by Ramsey-type measurements. The T2 relaxation time in the Rb vapor cell is found to be position dependent, and correlates with the gradient of the DC magnetic field. The presented method is highly useful for experimental in-situ characterization of DC magnetic fields and resonant microwave structures, for atomic clocks or other atom-based sensors and instrumentation.
description: 23 pages, 9 Figures in IEEE Transactions on Instrumentation and Measurement, 2015
Einband für die Briefe von Alphonse Henri Sinn (1869-?) an seinen Bruder Jules Sinn
Creators: name: Sinn, Alphonse Henri
Publisher: name: [s.n.]
Year: 1910

description: Deckel für Vorder- und Rückseite. Vorderdeckel mit Goldprägung: Alphonse Sinn, Ingénieur de Mines. Son 3ième voyage en Bolivie 1904-1905. Emblem.
Aus konservatorischen Gründen im 21. Jahrhundert von den Originalen getrennt
(1610) Joseph Hartley Wicksteed
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
Exploring new models in all detail with SARAH
Creators: name: Staub, Florian
Publisher: name: arXiv
Year: 2015
Subjects: subject: High Energy Physics - Phenomenology (hep-ph)
subject: High Energy Physics - Experiment (hep-ex)
subject: FOS: Physical sciences

description: I give an overview about the features the Mathematica package SARAH provides to study new models. In general, SARAH can handle a wide range of models beyond the MSSM coming with additional chiral superfields, extra gauge groups, or distinctive features like Dirac gaugino masses. All of these models can be implemented in a compact form in SARAH and are easy to use: SARAH extracts all analytical properties of the given model like two-loop renormalization group equations, tadpole equations, mass matrices and vertices. Also one- and two-loop corrections to tadpoles and self-energies can be obtained. For numerical calculations SARAH can be interfaced to other tools to get the mass spectrum, to check flavour or dark matter constraints, and to test the vacuum stability, or to perform collider studies. In particular, the interface to SPheno allows a precise prediction of the Higgs mass in a given model comparable to MSSM precision by incorporating the important two-loop corrections. I show in great detail at the example of the B-L-SSM how SARAH together with SPheno, HiggsBounds/HiggsSignals, FlavorKit, Vevacious, CalcHep, MicrOmegas, WHIZARD, and MadGraph can be used to study all phenomenological aspects of a model. Even if I concentrate in this manuscript on the analysis of supersymmetric models most features are also available in the non-supersymmetric case.
description: 169 pages, 14 figures; pedagogical summary of 0806.0538, 0909.2863, 1002.0840, 1109.5147, 1207.0906, 1307.1477, 1309.7223, 1405.1434, 1411.0675 and 1503.03098 prepared for "Supersymmetry, Supergravity, and Superstring Phenomenology"
Transforming Activity of the Rho Family GTPase, Wrch-1, a Wnt-regulated Cdc42 Homolog, Is Dependent on a Novel Carboxyl-terminal Palmitoylation Motif
Creators: name: Buss, Janice E.
name: Berzat, Anastacia C.
name: Minden, Audrey
name: Shutes, Adam
name: Cox, Adrienne D.
name: Weinbaum, Carolyn A.
name: Der, Charming J.
name: Chenette, Emily J.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2005

description: Wrch-1 is a Rho family GTPase that shares strong sequence and functional similarity with Cdc42. Like Cdc42, Wrch-1 can promote anchorage-independent growth transformation. We determined that activated Wrch-1 also promoted anchorage-dependent growth transformation of NIH 3T3 fibroblasts. Wrch-1 contains a distinct carboxyl-terminal extension not found in Cdc42, suggesting potential differences in subcellular location and function. Consistent with this, we found that Wrch-1 associated extensively with plasma membrane and endosomes, rather than with cytosol and perinuclear membranes like Cdc42. Like Cdc42, Wrch-1 terminates in a CAAX tetrapeptide (where C is cysteine, A is aliphatic amino acid, and X is any amino acid) motif (CCFV), suggesting that Wrch-1 may be prenylated similarly to Cdc42. Most surprisingly, unlike Cdc42, Wrch-1 did not incorporate isoprenoid moieties, and Wrch-1 membrane localization was not altered by inhibitors of protein prenylation. Instead, we showed that Wrch-1 is modified by the fatty acid palmitate, and pharmacologic inhibition of protein palmitoylation caused mislocalization of Wrch-1. Most interestingly, mutation of the second cysteine of the CCFV motif (CCFV > CSFV), but not the first, abrogated both Wrch-1 membrane localization and transformation. These results suggest that Wrch-1 membrane association, subcellular localization, and biological activity are mediated by a novel membrane-targeting mechanism distinct from that of Cdc42 and other isoprenylated Rho family GTPases.