gebhart/patrepeval huggingface dataset:
A Robust Error Model for iTRAQ Quantification Reveals Divergent Signaling between Oncogenic FLT3 Mutants in Acute Myeloid Leukemia (2009)

The FLT3 receptor tyrosine kinase plays an important role in normal hematopoietic development and leukemogenesis. Point mutations within the activation loop and in-frame tandem duplications of the juxtamembrane domain represent the most frequent molecular abnormalities observed in acute myeloid leukemia. Interestingly these gain-of-function mutations correlate with different clinical outcomes, suggesting that signals from constitutive FLT3 mutants activate different downstream targets. In principle, mass spectrometry offers a powerful means to quantify protein phosphorylation and identify signaling events associated with constitutively active kinases or other oncogenic events. However, regulation of individual phosphorylation sites presents a challenging case for proteomics studies whereby quantification is based on individual peptides rather than an average across different peptides derived from the same protein. Here we describe a robust experimental framework and associated error model for iTRAQ-based quantification on an Orbitrap mass spectrometer that relates variance of peptide ratios to mass spectral peak height and provides for assignment of p value, q value, and confidence interval to every peptide identification, all based on routine measurements, obviating the need for detailed characterization of individual ion peaks. Moreover, we demonstrate that our model is stable over time and can be applied in a manner directly analogous to ubiquitously used external mass calibration routines. Application of our error model to quantitative proteomics data for FLT3 signaling provides evidence that phosphorylation of tyrosine phosphatase SHP1 abrogates the transformative potential, but not overall kinase activity, of FLT3-D835Y in acute myeloid leukemia.
Determination of Coreceptor Usage of Human Immunodeficiency Virus Type 1 from Patient Plasma Samples by Using a Recombinant Phenotypic Assay (2001)

We developed a recombinant virus technique to determine the coreceptor usage of human immunodeficiency virus type 1 (HIV-1) from plasma samples, the source expected to represent the most actively replicating virus population in infected subjects. This method is not subject to selective bias associated with virus isolation in culture, a step required for conventional tropism determination procedures. The addition of a simple subcloning step allowed semiquantitative evaluation of virus populations with a different coreceptor (CCR5 or CXCR4) usage specificity present in each plasma sample. This procedure detected mixtures of CCR5- and CXCR4-exclusive virus populations as well as dualtropic viral variants, in variable proportions. Sequence analysis of dualtropic clones indicated that changes in the V3 loop are necessary for the use of CXCR4 as a coreceptor, but the overall context of the V1-V3 region is important to preserve the capacity to use CCR5. This convenient technique can greatly assist the study of virus evolution and compartmentalization in infected individuals.
Characterization of rat hypothalamic corticotropin-releasing factor. (1983)

A polypeptide was purified from rat hypothalamic extracts on the basis of its high intrinsic activity to release corticotropin (ACTH) from cultured rat anterior pituitary cells and its immunoactivity in a radioimmunoassay directed against the NH2 terminus (residues 4-20) of ovine hypothalamic corticotropin-releasing factor (CRF). Based on Edman degradation, peptide mapping, and amino acid analysis, the primary structure of this rat CRF was established to be: H-Ser-Glu-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu-Met-Glu-Ile-Ile-NH2. The hypophysiotropic potency of synthetic rat CRF did not deviate significantly from the potencies of the isolated native peptide or of synthetic ovine CRF. The close structural relationship between rat and ovine hypothalamic CRF is indicated by an 83% sequence homology.
Can CT Pulmonary Angiography Allow Assessment of Severity and Prognosis in Patients Presenting with Pulmonary Embolism? What the Radiologist Needs to Know (2006)

Computed tomographic (CT) pulmonary angiography has been established as a first-line diagnostic technique in patients suspected of having pulmonary embolism. Risk stratification is important in patients with pulmonary embolism because optimal management, monitoring, and therapeutic strategies depend on the prognosis. Acute right-sided heart failure is known to be responsible for circulatory collapse and death in patients with severe pulmonary embolism. Acute right-sided heart failure can be assessed at CT pulmonary angiography by measuring the dimensions of right-sided heart cavities or upstream venous structures, such as the superior vena cava or azygos vein. The magnitude of pulmonary embolism can be calculated at CT pulmonary angiography by applying angiographic scores adapted for CT (Miller and Walsh scores) or dedicated CT scores (Qanadli and Mastora scores). The advent of CT pulmonary angiography performed with electrocardiographic gating permits new advances in assessment of acute right-sided heart failure, such as measurement of the ventricular ejection fraction. Although such findings may be useful for assessment of treatment effectiveness, their effect on prognosis in patients with severe pulmonary embolism is debated in the literature.
Side Population Cells in the Mouse Thyroid Exhibit Stem/Progenitor Cell-Like Characteristics (2007)

Side population (SP) cells are characterized by their ability to efflux the vital dye Hoechst 33342 (Sigma-Aldrich, St. Louis, MO) due to expression of the ATP binding cassette (ABC)-dependent transporter ABCG2, and are highly enriched for stem/progenitor cell activity. In this study we identified SP cells in murine thyroid, which are composed of two populations of cells: CD45(-)/c-kit(-)/Sca1(+) and CD45(-)/c-kit(-)/Sca1(-) cells. Quantitative RT-PCR analysis revealed that SP cells highly express ABCG2 and the stem cell marker genes encoding nucleostemin and Oct4, whereas the expression of genes encoding the thyroid differentiation markers, thyroid peroxidase, thyroglobulin (TG), and TSH receptor, and two transcription factors, thyroid transcription factor 1 (TITF1) and paired PAX8, critical for thyroid specific gene expression, are low in SP cells as compared with the main population cells. In situ hybridization and double immunofluorescence demonstrated that cells expressing Abcg2 gene reside in the interfollicular space of the thyroid gland. Approximately half and a small percentage of the ABCG2-positive cells were also positive for vimentin and calcitonin, respectively. After 9 wk under three-dimensional thyroid primary culture conditions, main population cells formed an epithelial arrangement and follicle-like structures that are immunoreactive for TITF1 and TG. In contrast, SP cells demonstrated very few morphological changes without any epithelial or follicle-like structure and negative immunostaining for TITF1 and TG. These results demonstrate that thyroid possesses SP cells that may represent stem/progenitor cells.
Mutations within Potential Glycosylation Sites in the Capsid Protein of Hepatitis E Virus Prevent the Formation of Infectious Virus Particles (2007)

Hepatitis E virus is a nonenveloped RNA virus. However, the single capsid protein resembles a typical glycoprotein in that it contains a signal sequence and potential glycosylation sites that are utilized when recombinant capsid protein is overexpressed in cell culture. In order to determine whether these unexpected observations were biologically relevant or were artifacts of overexpression, we analyzed capsid protein produced during a normal viral replication cycle. In vitro transcripts from an infectious cDNA clone mutated to eliminate potential glycosylation sites were transfected into cultured Huh-7 cells and into the livers of rhesus macaques. The mutations did not detectably affect genome replication or capsid protein synthesis in cell culture. However, none of the mutants infected rhesus macaques. Velocity sedimentation analyses of transfected cell lysates revealed that mutation of the first two glycosylation sites prevented virion assembly, whereas mutation of the third site permitted particle formation and RNA encapsidation, but the particles were not infectious. However, conservative mutations that did not destroy glycosylation motifs also prevented infection. Overall, the data suggested that the mutations were lethal because they perturbed protein structure rather than because they eliminated glycosylation.
Longitudinal Study of Cerebral Metabolic Asymmetries and Associated Neuropsychological Patterns in Early Dementia of the Alzheimer Type (1990)

Regional cerebral metabolic rates for glucose (rCMRglc), as measured with positron emission tomography, and neuropsychological function were studied longitudinally (range, 15 to 48 months) in 11 mildly impaired patients with dementia of the Alzheimer type (DAT) and compared with results from patients with moderate and severe DAT and from controls. At initial evaluation, association cortex metabolic asymmetries were greater in patients with DAT than in controls for all dementia severities and correlated significantly with neuropsychological discrepancies between visuospatial and language abilities in patients with moderate dementia. In mildly impaired patients, right-left metabolic asymmetries in the association cortices were directionally stable and became more pronounced over time. At initial evaluation, these patients had significant impairment, relative to controls, on tests of memory and attention to complex tasks but not on tests of language and visuospatial function. Memory, attention, language, and visuospatial impairments, however, all worsened significantly over time. In mildly impaired patients, correlations between right-left metabolic asymmetries and neuropsychological discrepancies were insignificant initially but were significant at last evaluation. These results demonstrate that heterogeneous nonmemory language and visuospatial impairments in early DAT are related to and predicted by the earlier-appearing distribution of metabolic reductions in the association neocortex.
The Growth of Auditory Sensation (1947)

The integration of sensation with respect to time was studied experimentally by means of tones of short duration. Loudness tests were made on sounds persisting from 0.005 to 0.2 second and covering a wide range of levels. The observed increase in magnitude of a sensation as the duration time is increased is attributed to the integration characteristic of the central nervous system, and an equivalent electrical circuit is derived. The circuit analogy is then used in the computation of loudness as a function of the duration of the stimulus.
Highly nonlinear Ge-As-Se and Ge-As-S-Se glasses for all-optical switching (2002)

We have synthesized Ge-As-Se and Ge-As-S-Se chalcogenide glasses designed to have large optical nonlinearities. Measurements reveal that these glasses offer optical Kerr nonlinearities greater than 500 times that of fused silica and figures of merit for all-optical switching >5 at 1.25 and 1.55 μm.
Nanoporous three-dimensional networks topologically related to Cooperite from the self-assembly of copper(I) centres and the "‘square-planar’' building block 1,2,4,5-tetracyanobenzene (1999)

The deliberate assembly of a CuI 3D coordination network with the Cooperite (PtS) topology, namely [Cu(µ4-TCNB)][PF6] 1, has been accomplished by using the pseudo-square-planar building block 1,2,4,5-tetracyanobenzene (TCNB). It has been obtained by reacting [Cu(NCMe)4][PF6] with TCNB (in molar ratio 1:1) in solvent mixtures of CH2Cl2 and of a poorly basic solvent, like ethanol, isopropanol, benzyl alcohol or acetone. The crystals are orthorhombic, space group Cccm, with a=8.157(1), b=18.634(2), c=11.613(1) Å, Z=4. The framework is based on tetrahedral CuI centres and tetradentate µ4-TCNB ligands and presents cavities containing guest solvent molecules. On performing the same reaction in CH2Cl2–THF a 3D three-connected polymeric species, [Cu(µ3-TCNB)(THF)][PF6] 2, is obtained. Compound 2 gives monoclinic crystals, space group P21/c, with a=21.617(2), b=11.127(3), c=16.294(2) Å, β=111.61(2)°, Z=8. In 2 the TCNB ligands are tridentate and the copper centres achieve a tetrahedral coordination on forming a bond with a THF molecule. The network presents an unprecedented topology, (8210)-b, and the crystals undergo, by thermal activation, an unusual crystal-to-crystal transformation, losing the THF molecules to give the same frame as 1.
Disruption and mapping of IDI1, the gene for isopentenyl diphosphate isomerase in Saccharomyces cerevisiae (1992)

Isopentenyl diphosphate isomerase catalyses an essential activation step in the isoprene biosynthetic pathway. The Saccharomyces cerevisiae gene for isomerase, IDI1, was recently isolated and characterized (Anderson et al. J. Biol. Chem. 1989a, 264, 19169-19175). Wild-type IDI1 was disrupted with a LEU2 marker, and the resulting DNA was used to transform a yeast leucine auxotroph. Southern blots of EcoRI fragments of chromosomal DNA from the diploid strain showed the expected fragments for intact and disrupted IDI1. Dissection and analysis of tetrads demonstrated that IDI1 is an essential single-copy gene. A CHEF gel and clone grid filter analysis, followed by chromosomal mapping indicated that the gene is located on chromosome XVI approximately 55 kb centromere proximal to PEP4.
Prediction and verification of power/ground plane edge radiation excited by through-hole signal via based on balanced TLM and via coupling model (2003)

We introduce a modeling and simulation method to predict power/ground plane resonance and edge radiation coupled from the broken return current path of a through-hole signal via, and analyze the coupling and radiation mechanism. The approach is successfully verified with a series of measurements with various plane conditions.
Synthetic sulpholipopolysaccharides: novel adjuvants for humoral immune responses. (1987)

Referring to the strong immunostimulating activity of combinations of lipophilic agents and dextran sulphate, conjugates with chemical determinants of both types of adjuvants were synthesized and then examined for immunostimulatory capabilities in mice. Saturated fatty acids with varying chain lengths and sulphate groups were coupled covalently at defined ratios to the polysaccharide Ficoll (MW 400,000). Chemical analysis of 60 of the sulpholipopolysaccharides synthesized revealed that the number of sulphate groups per monosaccharide unit varied from 0 to 1.6, and the number of lipid groups from 0 to 0.8. Adjuvanticity of these conjugates for the humoral immune response was determined using sheep red blood cells (SRBC) and dinitrophenyl-haptenated bovine serum albumin (DNP-BSA) as antigens. Five days after intraperitoneal injection of adjuvant and antigen, the numbers of direct anti-SRBC plaque-forming cells (PFC) in the spleen were determined. Anti-DNP antibody titres were measured from 1 to 4 weeks after immunization. PFC responses to 2 X 10(6) SRBC were augmented up to a 100-fold by conjugates of Ficoll and sulphate (sulphopolysaccharides: SPs) or lipid groups (lipopolysaccharides: LPs). Introduction of low or moderate numbers of lipid groups in SPs reduced adjuvanticity. Adjuvant activity of sulpholipopolysaccharides (SLPs) with varying sulphate and high lipid content depended on the sulphate contents and the chain length of the lipids. Sulphate reduced adjuvanticity of the SLPs, and the number of sulphate groups required for complete annihilation increased with the chain length of the lipid. LPs and SLPs, including conjugates that did not enhance anti-SRBC PFC responses, augmented serum antibody responses to DNP-BSA while SPs were hardly effective.
Adhesion to E-selectin promotes growth inhibition and apoptosis of human and murine hematopoietic progenitor cells independent of PSGL-1 (2003)

Although both P- and E-selectin are constitutively expressed on bone marrow endothelial cells, their role in the regulation of hematopoiesis has only recently been investigated. We have previously shown that P-selectin glycoprotein ligand-l (PSGL-1/CD162) is expressed by primitive human bone marrow CD34+ cells, mediates their adhesion to P-selectin, and, more importantly, inhibits their proliferation. We now demonstrate that adhesion to E-selectin inhibits the proliferation of human CD34+ cells isolated either from human umbilical cord blood, adult mobilized blood, or steady-state bone marrow. Furthermore, a subpopulation, which does not contain the most primitive hematopoietic progenitor cells, undergoes apoptosis following E-selectin-mediated adhesion. The same phenomenon was observed in cells isolated from mouse bone marrow. Using lineage-negative Sca-1+ c-KIT+ bone marrow cells from PSGL-1(-/-) and wild-type mice, we establish that PSGL-1 is not the ligand involved in E-selectin-mediated growth inhibition and apoptosis. Moreover, stable transfection of the human myeloid cell line K562 (which does not express PSGL-1) with alpha(1,3) fucosyltransferase VII alone was sufficient to recapitulate the E-selectin-mediated growth inhibition and apoptosis observed in hematopoietic progenitor cells. These data demonstrate that an E-selectin ligand(s) other than PSGL-1 transduces growth inhibitory and proapoptotic signals and requires posttranslational fucosylation to be functional.
Effects of Transglutaminase on SDS‐PAGE Patterns of Wheat, Soy, and Barley Proteins and their Blends (2002)

ABSTRACT: Transglutaminase (TG) catalyzes the formation of nondisulfide covalent crosslinks between pep‐tide‐bound glutaminyl residues and ε‐amino groups of lysine residues in proteins. TG can be used for polymerizing proteins from 1 or more sources through formation of intermolecular crosslinks. This study investigated, by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis, polymers created by the action of TG on proteins of wheat, soy, barley, wheat‐soy, and wheat‐barley blends. Electrophoretic results showed that with increasing incubation time, the crosslinking reaction is substantially increased, with progressive decrease or disappearance of some protein monomers. Densitometric results showed that soy proteins were the best substrates of TG while barley and wheat proteins were similar in reactivity.
Kinetics and mechanism of interpolyelectrolyte exchange and addition reactions (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTKinetics and mechanism of interpolyelectrolyte exchange and addition reactionsK. N. Bakeev, V. A. Izumrudov, S. I. Kuchanov, A. B. Zezin, and V. A. KabanovCite this: Macromolecules 1992, 25, 17, 4249–4254Publication Date (Print):August 1, 1992Publication History Published online1 May 2002Published inissue 1 August 1992https://pubs.acs.org/doi/10.1021/ma00043a003https://doi.org/10.1021/ma00043a003research-articleACS PublicationsRequest reuse permissionsArticle Views654Altmetric-Citations142LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
A small-molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC delays leukemia in mice (2015)

Acute myeloid leukemia (AML) is the most common form of adult leukemia. The transcription factor fusion CBFβ-SMMHC (core binding factor β and the smooth-muscle myosin heavy chain), expressed in AML with the chromosome inversion inv(16)(p13q22), outcompetes wild-type CBFβ for binding to the transcription factor RUNX1, deregulates RUNX1 activity in hematopoiesis, and induces AML. Current inv(16) AML treatment with nonselective cytotoxic chemotherapy results in a good initial response but limited long-term survival. Here, we report the development of a protein-protein interaction inhibitor, AI-10-49, that selectively binds to CBFβ-SMMHC and disrupts its binding to RUNX1. AI-10-49 restores RUNX1 transcriptional activity, displays favorable pharmacokinetics, and delays leukemia progression in mice. Treatment of primary inv(16) AML patient blasts with AI-10-49 triggers selective cell death. These data suggest that direct inhibition of the oncogenic CBFβ-SMMHC fusion protein may be an effective therapeutic approach for inv(16) AML, and they provide support for transcription factor targeted therapy in other cancers.
Generation of a dominant 8-MDa deletion at the left terminus of vaccinia virus DNA. (1985)

Vaccinia virus mutants were obtained in high frequency from mouse Friend erythroleukemia (FEL) cells persistently infected with this virus, which contains a large (122-MDa) DNA. During long-term cell passages viral particles with deletions of the DNA are generated in FEL cells. These mutants have a major 8-MDa deletion starting between 2.2 and 3.2 MDa from the left terminus of the viral genome. More than half of the left end terminal repetition is deleted. These mutants have reduced infectivity compared to wild-type virus. The ease with which vaccinia virus mutants are obtained in FEL cells should provide a suitable system for generating mutants with other poxvirus and permit study of the genetic basis of virulence for this group of viruses.
The Amazing Transglycosylation Activity of Endo-β-N-Acetylglucosaminidases (2011)

Major advances have been made in exploring the transglycosylation activity of endo-β-N-acetylglucosaminidases (ENGases) for synthetic purpose. The exploration of synthetic sugar oxazolines as donor substrates for the ENGase-catalyzed transglycosylation has expanded the substrate availability and significantly enhanced the overall transglycosylation efficiency. On the other hand, site-directed mutagenesis in combination with activity screening has led to the discovery of the first generation ENGase-based glycosynthases that can use highly active sugar oxazolines as substrates for transglycosylation but lack hydrolytic activity on the ground-state products. ENGases have shown amazing flexibility in transglycosylation and possess much broader substrate specificity than previously thought. Now the ENGase-based chemoenzymatic method has been extended to the synthesis of a range of complex carbohydrates, including homogeneous glycopeptides, glycoproteins carrying well-defined glycans, novel oligosaccharide clusters, unusually glycosylated natural products, and even polysaccharides. This article highlights recent advances related to ENGase-catalyzed transglycosylation with a focus on their synthetic potential.