gebhart/patrepeval huggingface dataset:
Decreased MUC1 expression induces E-cadherin-mediated cell adhesion of breast cancer cell lines. (1998)

Two breast cancer cell lines, YMB-S and ZR-75-1S, were established in our laboratory. They proliferated in suspension culture without aggregation in a complete liquid medium. We found that sodium butyrate (NaB) arrested the cells in the G0-G1 phase of the cell cycle, inhibited their proliferation, and induced cell-cell and cell-surface adhesion. In this study, we explored the mechanism of this adhesion. Adhesion was inhibited by an anti-E-cadherin antibody, suggesting a role for E-cadherin. However, there were no changes in the expression of E-cadherin, alpha-catenin, and beta-catenin. Northern blot analysis and cytofluorometry revealed that NaB-treated cells showed a lower expression of MUC1 than did untreated cells. To examine the possibility that the adhesion of these cells might be induced by decreased MUC1 expression, the level of MUCI expression was directly reduced using an antisense oligonucleotide. The MUC1 antisense oligonucleotide induced cell-cell and cell-surface adhesion of these breast cancer cells, just as NaB did. Our observations indicate that E-cadherin can be functionally suppressed by overexpression of MUC1 but resumes its activity after suppression of MUC1 expression. Thus, regulation of MUC1 might be a new strategy for cancer therapy.
Holoprotein formation of human chorionic gonadotropin: differential trace labeling with acetic anhydride. (1994)

The effects of holoprotein formation in human CG (hCG) on the reactivities of several of the individual amino groups of each subunit were investigated by differential trace labeling with [3H]acetic anhydride. The alpha- and beta-subunits were labeled separately, as was hCG, under conditions chosen to ensure that an average of less than one amino group was modified per molecule. Although the beta-subunit contains fewer amino groups than the alpha-subunit, most of the 3H incorporation occurred in beta at the N-terminal region. Chemical and enzymatic cleavage of the subunits enabled us to identify several individual amino groups and, from measurements of the incorporated radioactivity of the free subunits and intact hormone, determine their protection factor, which is a measure of the reactivity and thus of the local environment and changes thereof upon holoprotein formation. Lys51 and Lys91 of alpha were approximately 2-fold more reactive and less reactive, respectively, in the alpha beta complex than in the free subunit. The alpha-amino group of alpha was characterized by comparable reactivities in the heterodimer and free subunit, as was Lys44/Lys45 when analyzed as a pair; the reactivity of alpha-Lys44 was slightly less in the holoprotein than in the free subunit. The alpha-amino group and Lys2 of beta could not be resolved by available cleavage procedures; consequently they were analyzed as a pair and found to be some 2-fold less reactive in the heterodimer than in the free subunit, as was Lys104 of beta. From these results, we can conclude that subunit assembly produces changes in the microenvironments of several amino groups, attributable to steric effects, specific intermolecular interactions, and localized conformational changes. Analysis of these data with reference to the recently determined crystal structure of hydrogen fluoride-treated hCG enabled a distinction to be made of these possibilities for several of the amino groups.
Developmental Self-Assembly of a DNA Tetrahedron (2014)

Kinetically controlled isothermal growth is fundamental to biological development, yet it remains challenging to rationally design molecular systems that self-assemble isothermally into complex geometries via prescribed assembly and disassembly pathways. By exploiting the programmable chemistry of base pairing, sophisticated spatial and temporal control have been demonstrated in DNA self-assembly, but largely as separate pursuits. By integrating temporal with spatial control, here we demonstrate the "developmental" self-assembly of a DNA tetrahedron, where a prescriptive molecular program orchestrates the kinetic pathways by which DNA molecules isothermally self-assemble into a well-defined three-dimensional wireframe geometry. In this reaction, nine DNA reactants initially coexist metastably, but upon catalysis by a DNA initiator molecule, navigate 24 individually characterizable intermediate states via prescribed assembly pathways, organized both in series and in parallel, to arrive at the tetrahedral final product. In contrast to previous work on dynamic DNA nanotechnology, this developmental program coordinates growth of ringed substructures into a three-dimensional wireframe superstructure, taking a step toward the goal of kinetically controlled isothermal growth of complex three-dimensional geometries.
Theory for the observed isotope effects on the formation of multiple products by different kinetic mechanisms of cytochrome P450 enzymes (1994)

Cytochrome P450 systems are unusual in that many of them can convert a substrate to a number of different metabolites. Several kinetic mechanisms may be envisioned by which the metabolites may be formed. In each of the mechanisms, the substrate combines with the enzyme in different orientations to form a set of (ES) complexes that then are activated to a set of (EOS) complexes. The fate of these (EOS) complexes determines the kinetic mechanism. In the "parallel pathway" mechanism, the (EOS) complexes are so stable and rigid they cannot be converted either directly or indirectly to complexes with different orientations; the orientation of the (ES) complexes thus determines which metabolite will be formed. In the "nondissociative" mechanisms, the complexes are not rigid; instead they undergo interconversion while the substrate remains in the active site of the enzyme. In the "dissociative" mechanisms, the (EOS) complexes dissociate to (EO) and (S), but recombine to form (EOS) complexes with either the same or different orientations. Steady-state equations describing the deuterium isotope effects for these kinetics mechanisms have been derived and solved for competitive experiments, in which equal concentrations of both deuterated and nondeuterated substrates are present in incubation mixtures, and for noncompetitive experiments, in which only one of the substrates is present. The equations reveal that comparisons of the isotope effects on the formation of a metabolite by a pathway that does not involve the abstraction of a deuterium from a deuterated substrate (the non-deuterium abstraction pathway) in both experiments can differentiate between the kinetic mechanisms. A value of 1.0 for (v)H/(v)D in the competitive experiment, but < 1.0 to > 1.0 for the value of (Vmax/Km)H/(Vmax/Km)D in the noncompetitive experiment, is diagnostic for the "dissociative" mechanisms. Values of 1.0 in both kinds of experiments are diagnostic for the "parallel pathway" mechanism. Values of < 1.0 in both types of experiments are diagnostic for the "nondissociative" mechanisms. The equations also predict possible unusual substrate-inhibitor interactions when the "dissociative" mechanism is operative.
An Introduction to Chemical Kinetics (2017)

This book is intended to give a relatively concise introduction to the main principles of chemical kinetics at a level suitable for any undergraduate chemistry student. Elementary reactions and their rates are introduced and explained using Simple Collision Theory. Rate laws and reaction mechanisms are covered in some detail, as are experimental methods and data analysis techniques for obtaining kinetic information across a broad range of timescales. More advanced topics are touched on very brieﬂy at various points in the text, but for the most part, is left for the reader to explore in more comprehensive texts.
A decision support tool for antibiotic therapy. (1995)

We developed a decision support tool to assist physicians anticipating the need for antibiotic therapy. The initial screen alerts physicians of pertinent patient information, provides direct access to other essential medical information, and stimulates clinical judgment by suggesting an antibiotic regimen. The decision support tool also suggests the dose and interval for any ordered antibiotics selected by the physicians. During a 7-month pilot study, all antibiotics for patients admitted to the Shock/Trauma/Respiratory Intensive Care Unit (STRICU) were ordered using the decision support tool. Clinical data from the study period and a 12-month control period (the previous year) were collected and compared. The decision support tool was used to order antibiotics 588 times during the study period and the suggested antibiotics were used 218 (37%) times. The computer suggested dosages were used over 90% of the time. The mean cost of antibiotics was $87.00 (p < 0.04) less per patient during the study period as compared to the control period. Prospective assessment revealed only 3 antibiotic adverse drug events (ADEs) (0.9%) among 336 study patients as compared to 15 ADEs (2.4%) among 626 control patients (p = 0.164).
The Molecular Basis of the Sparse Fur Mouse Mutation (1987)

The ornithine transcarbamylase-deficient sparse fur mouse is an excellent model to study the most common human urea cycle disorder. The mutation has been well characterized by both biochemical and enzymological methods, but its exact nature has not been revealed. A single base substitution in the complementary DNA for ornithine transcarbamylase from the sparse fur mouse has been identified by means of a combination of two recently described techniques for rapid mutational analysis. This strategy is simpler than conventional complementary DNA library construction, screening, and sequencing, which has often been used to find a new mutation. The ornithine transcarbamylase gene in the sparse fur mouse contains a C to A transversion that alters a histidine residue to an asparagine residue at amino acid 117.
Evaluation of Immunomodulators, Interferons and Known in Vitro SARS-CoV Inhibitors for Inhibition of SARS-Cov Replication in BALB/c Mice (2006)

Compounds approved for therapeutic use and in vitro inhibitors of severe acute respiratory syndrome coronavirus (SARS-CoV) were evaluated for inhibition in the mouse SARS-CoV replication model. A hybrid interferon, interferon alpha (IFN-alpha) B/D, and a mismatched double-stranded (ds) RNA interferon (IFN) inducer, Ampligen (poly I:poly C124), were the only compounds that potently inhibited virus titres in the lungs of infected mice as assessed by CPE titration assays. When mice were dosed intraperitoneally (i.p.) with IFN-alpha B/D once daily for 3 days beginning 4 h after virus exposure, SARS-CoV replication in the lungs of infected mice was reduced by 1 log10 at 10,000 and 32,000 IU; at the highest dose of 100,000 IU, virus lung titres were below detectable limits. Ampligen used i.p. at 10 mg/kg 4 h prior to virus exposure also reduced virus lung titres to below detectable limits. Nelfinavir, beta-D-N4-hydroxycytidine, calpain inhibitor VI, 3-deazaneplanocin A and Alferon (human leukocyte IFN-alpha-n3) did not significantly reduce lung virus titres in mice. Anti-inflammatory agents, chloroquine, amodiaquin and pentoxifylline, were also inactive in vivo, suggesting that although they may be useful in ameliorating the hyperinflammatory response induced by the virus infection, they will not significantly reduce the replication of the virus, the inducer of inflammatory response. Thus, anti-inflammatory agents may only be useful in treating virus lung infections if used in combination with agents that inhibit virus replication. In summary, the data suggest that induction of IFN by mismatched dsRNA or actual treatment with exogenous IFN-alpha can inhibit SARS-CoV replication in the lungs of mice.
Internalization and intracellular processing of an anti B‐cell lymphoma monoclonal antibody, ll2 (1994)

The successful clinical experience with antibody LL2 (an IgG2a, anti-B-cell lymphoma antibody) in radioimmunodetection and radioimmunotherapy suggests that this antibody may have potential as a carrier of cytotoxic agents. The internalization, cellular trafficking, and catabolism of this antibody in target human Burkitt lymphoma cells (Raji) were investigated. Internalization of intact antibody as well as of the F(ab')2 and Fab' fragments was detected by an FITC-labeled anti-mouse second antibody probe, and evaluated by fluorescence microscopy. Internalization of intact IgG (or the fragments) was observed as early as 5 min after incubation at 37 degrees C. Initially, the internalized antibodies were present as micro-particles inside the cell membrane, and were translocated to the lysosomal compartment within 2 hr. The anatomic location of the internalized antibody, before translocation to the lysosomal compartment, was deduced by comparing the fluorescence images obtained with the antibody to those obtained with fluorescent probes with known cellular distribution in a co-internalization study. A Golgi-like compartment was found to be involved in the translocation of the antibody. Cellular catabolism of the bound antibody was studied by using 125I-labeled antibody on the target cells. At 21 h, 40% of the radioactivity was released into the supernatant as degraded fragments. The observation suggested that the antibody was degraded mainly in the lysosomes, since the degradation was significantly inhibited in the presence of lysosomal inhibitors such as ammonium chloride or leupeptin. Subcellular fractionation of Raji cells after the binding of 125I-labeled LL2 indicated that the antibody was translocated to lysosomes as evidenced by SDS-PAGE. The rate of internalization (Ke) of LL2, and the re-expression of the antigen were determined. The rapid internalization of LL2 and the re-expression of the antigen suggest that this antibody may have potential as a therapeutic immunoconjugate, since it could deliver a higher accumulation of cytotoxic agents into lymphoma cells.
Treatment of Pemphigus Vulgaris with Protein A Immunoadsorption: Case Report of Long-Term History Showing Favorable Outcome (2005)

A pemphigus vulgaris (PV) patient with a 14-year history of severe and painful blistering of skin and mucous membranes as well as side effects from corticosteroids and concomitant immunosuppressive drug treatment was managed successfully by protein A immunoadsorption (IA). After 19 sessions of protein A IA, the patient showed remission of PV and healing of mucocutaneous lesions and the skin. The level of the pathogenic autoantibodies to the adhesion proteins desmoglein 1 (Dsg-1) and desmoglein 3 (Dsg-3) measured by ELISA and immunofluorescence microscopy revealed a significant removal of autoantibodies after each IA therapy. There was a weak rebound of anti-Dsg-1 and anti-Dsg-3 antibodies between IA sessions but an overall decrease over the period of IA therapy. This case demonstrates the effective use of protein A IA as an adjuvant and corticosteroid-sparing therapy in severe pemphigus refractory to standard immunosuppressive therapy and underscores the need for careful monitoring of autoantibodies.
The MYB46 Transcription Factor Is a Direct Target of SND1 and Regulates Secondary Wall Biosynthesis in Arabidopsis (2007)

We demonstrate that the Arabidopsis thaliana MYB46 transcription factor is a direct target of SECONDARY WALL-ASSOCIATED NAC DOMAIN PROTEIN1 (SND1), which is a key transcriptional activator regulating the developmental program of secondary wall biosynthesis. The MYB46 gene is expressed predominantly in fibers and vessels in stems, and its encoded protein is targeted to the nucleus and can activate transcription. MYB46 gene expression was shown to be regulated by SND1, and transactivation analysis demonstrated that SND1 as well as its close homologs were able to activate the MYB46 promoter. Electrophoretic mobility shift assays and chromatin immunoprecipitation experiments revealed that SND1 binds to the MYB46 promoter. Dominant repression of MYB46 caused a drastic reduction in the secondary wall thickening of fibers and vessels. Overexpression of MYB46 resulted in an activation of the biosynthetic pathways of cellulose, xylan, and lignin and concomitantly led to ectopic deposition of secondary walls in cells that are normally nonsclerenchymatous. In addition, the expression of two secondary wall-associated transcription factors, MYB85 and KNAT7, was highly upregulated by MYB46 overexpression. These results demonstrate that MYB46 is a direct target of SND1 and is another key player in the transcriptional network involved in the regulation of secondary wall biosynthesis in Arabidopsis.
Allocation of ATP to synthesis of cells and hydrolytic enzymes in cellulolytic fermentative microorganisms: Bioenergetics, kinetics, and bioprocessing (1998)

Under anaerobic, carbon limited conditions, celluloytic fermentative microorganisms face a metabolic choice with respect to the allocation of relatively scarce ATP: to invest it in cells or in hydrolytic enzymes. A model is proposed that defines an allocation parameter reflecting the fractional expenditure of ATP on cell synthesis relative to the total ATP available (gross ATP synthesized less maintenance). This parameter is then incorporated into an ATP-centered model of anaerobic cellulose fermentation based on the ethanol fermentation of yeast and the cellulase system of Trichoderma reesei. Results indicate that high processing rates are possible via a consolidated bioprocessing strategy, especially at high cellulase specific activities, and that cell/cellulase allocation represents an interesting system in which to study, and perhaps exploit, microbial evolution and metabolic control. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 58:316–320, 1998.
Correlation of Cellular Immune Responses with Protection against Culture-Confirmed Influenza Virus in Young Children (2008)

The highly sensitive gamma interferon (IFN-gamma) enzyme-linked immunosorbent spot (ELISPOT) assay permits the investigation of the role of cell-mediated immunity (CMI) in the protection of young children against influenza. Preliminary studies of young children confirmed that the IFN-gamma ELISPOT assay was a more sensitive measure of influenza memory immune responses than serum antibody and that among seronegative children aged 6 to <36 months, an intranasal dose of 10(7) fluorescent focus units (FFU) of a live attenuated influenza virus vaccine (CAIV-T) elicited substantial CMI responses. A commercial inactivated influenza virus vaccine elicited CMI responses only in children with some previous exposure to related influenza viruses as determined by detectable antibody levels prevaccination. The role of CMI in actual protection against community-acquired, culture-confirmed clinical influenza by CAIV-T was investigated in a large randomized, double-blind, placebo-controlled dose-ranging efficacy trial with 2,172 children aged 6 to <36 months in the Philippines and Thailand. The estimated protection curve indicated that the majority of infants and young children with >or=100 spot-forming cells/10(6) peripheral blood mononuclear cells were protected against clinical influenza, establishing a possible target level of CMI for future influenza vaccine development. The ELISPOT assay for IFN-gamma is a sensitive and reproducible measure of CMI and memory immune responses and contributes to establishing requirements for the future development of vaccines against influenza, especially those used for children.
Reconstitution of a functional interleukin (IL)‐7 receptor demonstrates that the IL‐2 receptor γ chain is required for IL‐7 signal transduction (1995)

The interleukin (IL)-2 receptor gamma chain has recently been shown to be a component of the IL-7 and IL-4 receptors. Using a transient transfection assay and the trans-activation of reporter gene constructs which are under the control of cytokine-responsive promoter elements, we have studied signal transduction through the IL-7 receptor (IL-7R). The reporter gene expression was not stimulated by receptors that contained the cytoplasmic domain of the IL-7R, either as intact IL-7R or as part of a chimeric receptor. However, co-expression of the IL-7R with the IL-2 receptor gamma chain was able to stimulate gene activation. For maximal stimulation the intact cytoplasmic domains of each chain was required.
The combinatorial synthesis and chemical and biological evaluation of a 1,4-benzodiazepine library. (1994)

A library of 192 structurally diverse 1,4-benzodiazepine derivatives containing a variety of chemical functionalities including amides, carboxylic acids, amines, phenols, and indoles was constructed from three components, 2-aminobenzophenones, amino acids, and alkylating agents, by employing Geysen's pin apparatus [Geysen, H. M., Rodda, S. J., Mason, T. J., Tribbick, G. & Schoofs, P. G. (1987) J. Immunol. Methods 102, 259-274]. Rigorous analytical verification of the chemical integrity and yield of a representative collection of the diverse derivatives was carried out. In addition, the library of derivatives was evaluated for binding to the cholecystokinin A receptor by employing a competitive radio-ligand binding assay. This provided detailed structure versus activity relationships that were confirmed by independent large-scale synthesis and evaluation of several of the 1,4-benzodiazepine derivatives.
Targeted next-generation sequencing of a cancer transcriptome enhances detection of sequence variants and novel fusion transcripts (2009)

Targeted RNA-Seq combines next-generation sequencing with capture of sequences from a relevant subset of a transcriptome. When testing by capturing sequences from a tumor cDNA library by hybridization to oligonucleotide probes specific for 467 cancer-related genes, this method showed high selectivity, improved mutation detection enabling discovery of novel chimeric transcripts, and provided RNA expression data. Thus, targeted RNA-Seq produces an enhanced view of the molecular state of a set of "high interest" genes.
[Thieno[2,3-d]pyrimidines as antagonists of the glutamate receptors]. (2008)

Although the function of the kainate receptors in the brain is still not clear, they are increasingly defined as targets in the development of new classes of anti-epileptics. The thienopyrimidines described in this report were tested for their antagonistic effect at the kainate receptor subtypes GluR5 and GluR6. The highest effectiveness was obtained by a 4-ethoxy-thieno[2,3-d]pyrimidin with an IC50 = 68 microM at the GluR6 receptor.
Functional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients (2016)

This work demonstrates the feasibility of a prognostic and/or diagnostic platform combining the direct identification of AR mutants from patients' serum, and the functional characterization of these mutants in order to provide personalized recommendations regarding the best future therapy.
Sophorolipids, Microbial Glycolipids with Anti-Human Immunodeficiency Virus and Sperm-Immobilizing Activities (2005)

The increased incidence of human immunodeficiency virus (HIV)/AIDS disease in women aged 15 to 49 years has identified the urgent need for a female-controlled, efficacious, and safe vaginal topical microbicide. To meet this challenge, sophorolipid (SL) produced by Candida bombicola and its structural analogs have been studied in this report for their spermicidal, anti-HIV, and cytotoxic activities. The sophorolipid diacetate ethyl ester derivative is the most potent spermicidal and virucidal agent of the series of SLs studied. Its virucidal activity against HIV and sperm-immobilizing activity against human semen are similar to those of nonoxynol-9. However, it also induced enough vaginal cell toxicity to raise concerns about its applicability for long-term microbicidal contraception. Its structure-activity relationship has been established for creating new analogs with less cytotoxicity and higher activity.