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Dartmouth College

1997

Articles 1 - 20 of 20

Full-Text Articles in Medicine and Health Sciences

A Dichotomous Role For Nitric Oxide During Acute Toxoplasma Gondii Infection In Mice, Imtiaz A. Khan, Joseph D. Schwartzman, Tadashi Matsuura, Lloyd H. Kasper Dec 1997

A Dichotomous Role For Nitric Oxide During Acute Toxoplasma Gondii Infection In Mice, Imtiaz A. Khan, Joseph D. Schwartzman, Tadashi Matsuura, Lloyd H. Kasper

Dartmouth Scholarship

Production of nitric oxide by macrophages is believed to be an important microbicidal mechanism for a variety of intracellular pathogens, including Toxoplasma gondii. Mice with a targeted disruption of the inducible nitric oxide synthase gene (iNOS) were infected orally with T. gondii tissue cysts. Time to death was prolonged compared with parental controls. Histologic analysis of tissue from infected mice showed scattered small foci of inflammation with parasites in various tissues of iNOS−/− mice, whereas tissue from the parental C57BL/6 mice had more extensive tissue inflammation with few visible parasites. In particular, extensive ulceration and necrosis of distal small …

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Mitotic Spindle Poles Are Organized By Structural And Motor Proteins In Addition To Centrosomes, Tirso Gaglio, Mary A. Dionne, Duane A. Duane A. Compton Sep 1997

Mitotic Spindle Poles Are Organized By Structural And Motor Proteins In Addition To Centrosomes, Tirso Gaglio, Mary A. Dionne, Duane A. Duane A. Compton

Dartmouth Scholarship

The focusing of microtubules into mitotic spindle poles in vertebrate somatic cells has been assumed to be the consequence of their nucleation from centrosomes. Contrary to this simple view, in this article we show that an antibody recognizing the light intermediate chain of cytoplasmic dynein (70.1) disrupts both the focused organization of microtubule minus ends and the localization of the nuclear mitotic apparatus protein at spindle poles when injected into cultured cells during metaphase, despite the presence of centrosomes. Examination of the effects of this dynein-specific antibody both in vitro using a cell-free system for mitotic aster assembly and in …

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A Novel Polymorphism Of Fcgammariiia (Cd16) Alters Receptor Function And Predisposes To Autoimmune Disease, Jianming Wu, Jeffrey C. Edberg, Patricia B. Redecha, Vipin Bansal, Paul M. Guyre, Kimberly Coleman, Jane E. Salmon, Robert P. Kimberly Sep 1997

A Novel Polymorphism Of Fcgammariiia (Cd16) Alters Receptor Function And Predisposes To Autoimmune Disease, Jianming Wu, Jeffrey C. Edberg, Patricia B. Redecha, Vipin Bansal, Paul M. Guyre, Kimberly Coleman, Jane E. Salmon, Robert P. Kimberly

Dartmouth Scholarship

A novel polymorphism in the extracellular domain 2 (EC2) of FcgammaRIIIA affects ligand binding by natural killer (NK) cells and monocytes from genotyped homozygous normal donors independently of receptor expression. The nonconservative T to G substitution at nucleotide 559 predicts a change of phenylalanine (F) to valine (V) at amino acid position 176. Compared with F/F homozygotes, FcgammaRIIIa expressed on NK cells and monocytes in V/V homozygotes bound more IgG1 and IgG3 despite identical levels of receptor expression. In response to a standard aggregated human IgG stimulus, FcgammaRIIIa engagement on NK cells from V/V (high-binding) homozygotes led to a larger …

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Cell Signaling Pathways Elicited By Asbestos, B T. Mossman, S Faux, Y Janssen, L A. Jimenez, Cynthia Timblin, Christine Zanella, Jonathan Goldberg, Eric Walsh, Aaron Barchowsky, Kevin Driscoll Sep 1997

Cell Signaling Pathways Elicited By Asbestos, B T. Mossman, S Faux, Y Janssen, L A. Jimenez, Cynthia Timblin, Christine Zanella, Jonathan Goldberg, Eric Walsh, Aaron Barchowsky, Kevin Driscoll

Dartmouth Scholarship

In recent years, it has become apparent that minerals can trigger alterations in gene expression by initiating signaling events upstream of gene transactivation. These cascades may be initiated at the cell surface after interaction of minerals with the plasma membrane either through receptorlike mechanisms or integrins. Alternatively, signaling pathways may be stimulated by active oxygen species generated both during phagocytosis of minerals and by redox reactions on the mineral surface. At least two signaling cascades linked to activation of transcription factors, i.e., DNA-binding proteins involved in modulating gene expression and DNA replication, are stimulated after exposure of lung cells to …

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Increased Focal Adhesion Kinase- And Urokinase-Type Plasminogen Activator Receptor-Associated Cell Signaling In Endothelial Cells Exposed To Asbestos, A Barchowsky, B M. Lannon, L C. Elmore, M D. Treadwell Sep 1997

Increased Focal Adhesion Kinase- And Urokinase-Type Plasminogen Activator Receptor-Associated Cell Signaling In Endothelial Cells Exposed To Asbestos, A Barchowsky, B M. Lannon, L C. Elmore, M D. Treadwell

Dartmouth Scholarship

Exposure of low-passage endothelial cells in culture to nonlethal amounts of asbestos, but not refractory ceramic fiber-1, increases cell motility and gene expression. These changes may be initiated by the fibers mimicking matrix proteins as ligands for receptors on the cell surface. In the present study, 1- to 3-hr exposures of endothelial cells to 5 mg/cm2 of chrysotile asbestos caused marked cell elongation and motility. However, little morphological change was seen when chrysotile was added to cells pretreated with either mannosamine to prevent assembly of glycophosphatidylinositol (GPI)-anchored receptors or with herbimycin A to inhibit tyrosine kinase activity. Affinity purification of …

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Sqt1, Which Encodes An Essential Wd Domain Protein Of Saccharomyces Cerevisiae, Suppresses Dominant-Negative Mutations Of The Ribosomal Protein Gene Qsr1., Dominic P. Eisinger, Frederick A. Dick, Elke Denke, Bernard L. Trumpower Sep 1997

Sqt1, Which Encodes An Essential Wd Domain Protein Of Saccharomyces Cerevisiae, Suppresses Dominant-Negative Mutations Of The Ribosomal Protein Gene Qsr1., Dominic P. Eisinger, Frederick A. Dick, Elke Denke, Bernard L. Trumpower

Dartmouth Scholarship

QSR1 is an essential Saccharomyces cerevisiae gene, which encodes a 60S ribosomal subunit protein required for joining of 40S and 60S subunits. Truncations of QSR1 predicted to encode C-terminally truncated forms of Qsr1p do not substitute for QSR1 but do act as dominant negative mutations, inhibiting the growth of yeast when expressed from an inducible promoter. The dominant negative mutants exhibit a polysome profile characterized by 'half-mer' polysomes, indicative of a subunit joining defect like that seen in other qsr1 mutants (D. P. Eisinger, F. A. Dick, and B. L. Trumpower, Mol. Cell. Biol. 17:5136-5145, 1997.) By screening a high-copy …

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Qsr1p, A 60s Ribosomal Subunit Protein, Is Required For Joining Of 40s And 60s Subunits., Dominic P. Eisinger, Frederick A. Dick, Bernard L. Trumpower Sep 1997

Qsr1p, A 60s Ribosomal Subunit Protein, Is Required For Joining Of 40s And 60s Subunits., Dominic P. Eisinger, Frederick A. Dick, Bernard L. Trumpower

Dartmouth Scholarship

QSR1 is a recently discovered, essential Saccharomyces cerevisiae gene, which encodes a 60S ribosomal subunit protein. Thirty-one unique temperature-sensitive alleles of QSR1 were generated by regional codon randomization within a conserved 20-amino-acid sequence of the QSR1-encoded protein. The temperature-sensitive mutants arrest as viable, large, unbudded cells 24 to 48 h after a shift to 37 degrees C. Polysome and ribosomal subunit analysis by velocity gradient centrifugation of lysates from temperature-sensitive qsr1 mutants and from cells in which Qsr1p was depleted by down regulation of an inducible promoter revealed the presence of half-mer polysomes and a large pool of free 60S …

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The Type 2 Iodothyronine Deiodinase Is Expressed Primarily In Glial Cells In The Neonatal Rat Brain, Ana Guadaño-Ferraz, Maria Jesus Obregón, Donald L. St. Germain, Juan Bernal Sep 1997

The Type 2 Iodothyronine Deiodinase Is Expressed Primarily In Glial Cells In The Neonatal Rat Brain, Ana Guadaño-Ferraz, Maria Jesus Obregón, Donald L. St. Germain, Juan Bernal

Dartmouth Scholarship

Thyroid hormone plays an essential role in mammalian brain maturation and function, in large part by regulating the expression of specific neuronal genes. In this tissue, the type 2 deiodinase (D2) appears to be essential for providing adequate levels of the active thyroid hormone 3,5,3′-triiodothyronine (T3) during the developmental period. We have studied the regional and cellular localization of D2 mRNA in the brain of 15-day-old neonatal rats. D2 is expressed in the cerebral cortex, olfactory bulb, hippocampus, caudate, thalamus, hypothalamus, and cerebellum and was absent from the white matter. At the cellular level, D2 is expressed predominantly, if not …

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Assembly And Regulation Of The Cd40 Receptor Complex In Human B Cells, Michelle R. Kuhné, Michael Robbins, John E. Hambor, Matthew F. Mackey, Yoko Kosaka, Toshihide Nishimura, Jason P. Gigley, Randolph J. Noelle, David M. Calderhead Jul 1997

Assembly And Regulation Of The Cd40 Receptor Complex In Human B Cells, Michelle R. Kuhné, Michael Robbins, John E. Hambor, Matthew F. Mackey, Yoko Kosaka, Toshihide Nishimura, Jason P. Gigley, Randolph J. Noelle, David M. Calderhead

Dartmouth Scholarship

CD40 is a member of the tumor necrosis factor (TNF) receptor superfamily. Studies with human B cells show that the binding of CD154 (gp39, CD40L) to CD40 recruits TNF receptor– associated factor 2 (TRAF2) and TRAF3 to the receptor complex, induces the downregulation of the nonreceptor-associated TRAFs in the cell and induces an increased expression of Fas on the cell surface. Combined signaling through the interluekin 4 receptor and CD40 induces an increased expression of Fas with a commensurate increase in the level of TRAF2, but not TRAF3, that is recruited to the receptor complex. In contrast, engagement of the …

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Analysis Of Enhancer Function Of The Hs-40 Core Sequence Of The Human Alpha-Globin Cluster, Hsiaoli Chen, Christopher H. Lowrey, George Stamatoyannopoulos Jul 1997

Analysis Of Enhancer Function Of The Hs-40 Core Sequence Of The Human Alpha-Globin Cluster, Hsiaoli Chen, Christopher H. Lowrey, George Stamatoyannopoulos

Dartmouth Scholarship

HS-40 is the major regulatory element of the human α-globin locus, located 40 kb upstream of the ζ-globin gene. To test for potential interactions between HS-40 and the β- or the γ-globin gene promoters in stable transfection assays, the HS-40 core sequence was cloned upstream of either the β promoter or the γ promoter driving the neomycin phosphotransferase gene and enhancer activity was measured using a colony assay. In K562 or in MEL cells, enhancer activity of HS-40 was higher than that of the individual core sequences of the DNase I hypersensitive sites (HS) of the β-globin locus control region …

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The Glucose Transporter Glut4 And The Aminopeptidase Vp165 Colocalise In Tubulo-Vesicular Elements In Adipocytes And Cardiomyocytes, Sally Martin, Jacqueline E. Rice, Gwyn W. Gould, Susanna R. Keller Jun 1997

The Glucose Transporter Glut4 And The Aminopeptidase Vp165 Colocalise In Tubulo-Vesicular Elements In Adipocytes And Cardiomyocytes, Sally Martin, Jacqueline E. Rice, Gwyn W. Gould, Susanna R. Keller

Dartmouth Scholarship

The aminopeptidase vp165 is one of the major polypeptides enriched in GLUT4-containing vesicles immuno-isolated from adipocytes. In the present study we have confirmed and quantified the high degree of colocalisation between GLUT4 and vp165 using double label immuno-electron microscopy on vesicles isolated from adipocytes and heart. The percentage of vp165-containing vesicles that also contained GLUT4 was 91%, 76%, and 86% in rat adipocytes, 3T3-L1 adipocytes, and rat heart, respectively. Internalisation of a transferrin/HRP (Tf/HRP) conjugate by 3T3-L1 adipocytes, followed by diaminobenzidine treatment in intact cells, resulted in ablation of only 41% and 45% of GLUT4 and vp165, respectively, whereas endosomal …

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Identification Of A Novel Antiapoptotic Functional Domain In Simian Virus 40 Large T Antigen., Suzanne D. Conzen, Christine A. Snay, Charles N. Cole Jun 1997

Identification Of A Novel Antiapoptotic Functional Domain In Simian Virus 40 Large T Antigen., Suzanne D. Conzen, Christine A. Snay, Charles N. Cole

Dartmouth Scholarship

The ability of DNA tumor virus proteins to trigger apoptosis in mammalian cells is well established. For example, transgenic expression of a simian virus 40 (SV40) T-antigen N-terminal fragment (N-termTag) is known to induce apoptosis in choroid plexus epithelial cells. SV40 T-antigen-induced apoptosis has generally been considered to be a p53-dependent event because cell death in the brain is greatly diminished in a p53-/- background strain and is abrogated by expression of wild-type (p53-binding) SV40 T antigen. We now show that while N-termTags triggered apoptosis in rat embryo fibroblasts cultured in low serum, expression of full-length T antigens unable to …

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Human Immunodeficiency Virus Type 1 Infection Of Cells And Tissues From The Upper And Lower Human Female Reproductive Tract, Alexandra L. Howell, Robert D. Edkins, Sherry E. Rier, Grant R. Yeaman, Judy E. Stern, Michael W. Fanger, Charles R. Wira May 1997

Human Immunodeficiency Virus Type 1 Infection Of Cells And Tissues From The Upper And Lower Human Female Reproductive Tract, Alexandra L. Howell, Robert D. Edkins, Sherry E. Rier, Grant R. Yeaman, Judy E. Stern, Michael W. Fanger, Charles R. Wira

Dartmouth Scholarship

Viable tissue sections and isolated cell cultures from the human fallopian tube, uterus, cervix, and vaginal mucosa were examined for susceptibility to infection with human immunodeficiency virus type 1 (HIV-1). We examined infectivity by using the monocytotropic strain HIV-1JR-FLand several primary isolates of HIV-1 obtained from infected neonates. HIV-1 infection was measured by p24 production in short-term culture and by immunofluorescence detection of HIV-1 Nef and p24 proteins by laser scanning confocal microscopy. Three-color immunofluorescence was used to phenotype HIV-infected cells within tissue sections from each site. Our findings indicate that epithelial, stromal, and dendritic cells and cells …

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Dissection Of A Circadian Oscillation Into Discrete Domains, Martha W. Merrow, Norman Y. Garceau, Jay C. Dunlap Apr 1997

Dissection Of A Circadian Oscillation Into Discrete Domains, Martha W. Merrow, Norman Y. Garceau, Jay C. Dunlap

Dartmouth Scholarship

The circadian oscillator in Neurospora is a negative feedback loop involving as principal players the products of the frequency (frq) locus. frq encodes multiple forms of its protein product FRQ, which act to depress the amounts of frq transcript. In this scheme there are two discrete and separable steps to the circadian cycle, negative feedback itself (repression) in which FRQ acts to decrease the levels of its own transcript, and recovery from repression (derepression) in which frq transcript levels return to peak amounts. By introducing an exogenously regulatable frq transgene into a frq loss-of-function strain (frq9 …

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Sch 48973: A Potent, Broad-Spectrum, Antienterovirus Compound., Peter J. Buontempo, Stuart Cox, Jacquelyn Wright-Minogue, Jason L. Demartino, Angela M. Skelton, Eric Ferrari, Randi Albin, Edward J. Rozhon, V. Girijavallabhan, John F. Modlin, John F. O'Connell Mar 1997

Sch 48973: A Potent, Broad-Spectrum, Antienterovirus Compound., Peter J. Buontempo, Stuart Cox, Jacquelyn Wright-Minogue, Jason L. Demartino, Angela M. Skelton, Eric Ferrari, Randi Albin, Edward J. Rozhon, V. Girijavallabhan, John F. Modlin, John F. O'Connell

Dartmouth Scholarship

SCH 48973 is a novel molecule with potent, selective, antienterovirus activity. In assays of the cytopathic effect against five picornaviruses, SCH 48973 had antiviral activity (50% inhibitory concentrations [IC50s]) of 0.02 to 0.11 microg/ml, with no detectable cytotoxicity at 50 microg/ml. SCH 48973 inhibited 80% of 154 recent human enterovirus isolates at an IC50 of 0.9 microg/ml. The antiviral activity of SCH 48973 is derived from its specific interaction with viral capsid, as confirmed by competition binding studies. The affinity constant (Ki) for SCH 48973 binding to poliovirus was 8.85 x 10(-8) M. In kinetic studies, a maximum of approximately …

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Where Do Elderly Veterans Obtain Care For Acute Myocardial Infarction: Department Of Veterans Affairs Or Medicare?, S M. Wright, J Daley, E S. Fisher, G E. Thibault Feb 1997

Where Do Elderly Veterans Obtain Care For Acute Myocardial Infarction: Department Of Veterans Affairs Or Medicare?, S M. Wright, J Daley, E S. Fisher, G E. Thibault

Dartmouth Scholarship

To examine Department of Veterans Affairs (VA) and Medicare hospitalizations for elderly veterans with acute myocardial infarction (AMI), their use of cardiac procedures in both systems, and patient mortality. DATA SOURCES: Merging of inpatient discharge abstracts obtained from VA Patient Treatment Files (PTF) and Medicare MedPAR Part A files. A retrospective cohort study of male veterans 65 years or older who were prior users of the VA medical system (veteran-users) and who were initially admitted to a VA or Medicare hospital with a primary diagnosis of AMI at some time from January 1, 1988 through December 31, 1990 (N = …

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C-Terminal Truncations Of The Yeast Nucleoporin Nup145p Produce A Rapid Temperature-Conditional Mrna Export Defect And Alterations To Nuclear Structure., Thomas C. Dockendorff, Catherine V. Heath, Alan L. Goldstein, Christine A. Snay, C N. Cole Feb 1997

C-Terminal Truncations Of The Yeast Nucleoporin Nup145p Produce A Rapid Temperature-Conditional Mrna Export Defect And Alterations To Nuclear Structure., Thomas C. Dockendorff, Catherine V. Heath, Alan L. Goldstein, Christine A. Snay, C N. Cole

Dartmouth Scholarship

A screen for temperature-sensitive mutants of Saccharomyces cerevisiae defective in nucleocytoplasmic trafficking of poly(A)+ RNA has identified an allele of the NUP145 gene, which encodes an essential nucleoporin. NUP145 was previously identified by using a genetic synthetic lethal screen (E. Fabre, W. C. Boelens, C. Wimmer, I. W. Mattaj, and E. C. Hurt, Cell 78:275-289, 1994) and by using a monoclonal antibody which recognizes the GLFG family of vertebrate and yeast nucleoporins (S. R. Wente and G. Blobel, J. Cell Biol. 125:955-969, 1994). Cells carrying the new allele, nup145-10, grew at 23 and 30 degrees C but were unable to …

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A Heterodimer Of Thioredoxin And Ib2 Cooperates With Sec18p (Nsf) To Promote Yeast Vacuole Inheritance, Zuoyu Xu, Andreas Mayer, Eric Muller, William Wickner Jan 1997

A Heterodimer Of Thioredoxin And Ib2 Cooperates With Sec18p (Nsf) To Promote Yeast Vacuole Inheritance, Zuoyu Xu, Andreas Mayer, Eric Muller, William Wickner

Dartmouth Scholarship

Early in S phase, the vacuole (lysosome) of Saccharomyces cerevisiae projects a stream of vesicles and membranous tubules into the bud where they fuse and establish the daughter vacuole. This inheritance reaction can be studied in vitro with isolated vacuoles. Rapid and efficient homotypic fusion between saltwashed vacuoles requires the addition of only two purified soluble proteins, Sec18p (NSF) and LMA1, a novel heterodimer with a thioredoxin subunit. We now report the identity of the second subunit of LMA1 as IB2, a previously identified cytosolic inhibitor of vacuolar proteinase B. Both subunits are needed for efficient vacuole inheritance in vivo …

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Analysis Of Mutant Platelet-Derived Growth Factor Receptors Expressed In Pc12 Cells Identifies Signals Governing Sodium Channel Induction During Neuronal Differentiation., Gary R. Fanger, Richard R. Vaillancourt, Lynn E. Heasley, Jean-Pierre P. Montmayeur, Gary L. Johnson, Robert A. Maue Jan 1997

Analysis Of Mutant Platelet-Derived Growth Factor Receptors Expressed In Pc12 Cells Identifies Signals Governing Sodium Channel Induction During Neuronal Differentiation., Gary R. Fanger, Richard R. Vaillancourt, Lynn E. Heasley, Jean-Pierre P. Montmayeur, Gary L. Johnson, Robert A. Maue

Dartmouth Scholarship

The mechanisms governing neuronal differentiation, including the signals underlying the induction of voltage-dependent sodium (Na+) channel expression by neurotrophic factors, which occurs independent of Ras activity, are not well understood. Therefore, Na+ channel induction was analyzed in sublines of PC12 cells stably expressing platelet-derived growth factor (PDGF) beta receptors with mutations that eliminate activation of specific signalling molecules. Mutations eliminating activation of phosphatidylinositol 3-kinase (PI3K), phospholipase C gamma (PLC gamma), the GTPase-activating protein (GAP), and Syp phosphatase failed to diminish the induction of type II Na+ channel alpha-subunit mRNA and functional Na+ channel expression by PDGF, as determined by RNase …

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Cyclic Amp And Its Receptor Protein Negatively Regulate The Coordinate Expression Of Cholera Toxin And Toxin-Coregulated Pilus In Vibrio Cholerae, Karen Skorupski, Ronald K. Taylor Jan 1997

Cyclic Amp And Its Receptor Protein Negatively Regulate The Coordinate Expression Of Cholera Toxin And Toxin-Coregulated Pilus In Vibrio Cholerae, Karen Skorupski, Ronald K. Taylor

Dartmouth Scholarship

Insertion mutations in two Vibrio cholerae genes, cya and crp, which encode adenylate cyclase and the cyclic AMP (cAMP) receptor protein (CRP), respectively, derepressed the expression of a chromosomal cholera toxin (CT) promoter-lacZ fusion at the nonpermissive temperature of 37 degrees C. In the classical biotype strain O395, the crp mutation increased the production of both CT and toxin-coregulated pilus (TCP) in vitro under a variety of growth conditions not normally permissive for their expression. The most dramatic increase in CT and TCP was observed with the crp mutant in Luria-Bertani (LB) medium pH 8.5, at 30 degrees C. El …

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