gebhart/patrepeval huggingface dataset:
Comparison of ccd of F, parDE of RP4, and parD of R1 using a novel conditional replication control system of plasmid R1 (1995)

A number of plasmid-encoded gene systems are thought to stabilize plasmids by killing plasmid-free cells (also termed post-segregational killing or plasmid addiction). Here we analyse the mechanisms of plasmid stabilization by ccd of F, parDE of RP4 and parD of R1, and compare them to hok/sok of R1. To induce synchronous plasmid loss we constructed a novel plasmid replication-arrest system, which possesses the advantage that plasmid replication can be completely arrested by the addition of IPTG, a non-metabolizable inducer. Using isogenic plasmid constructions we have found, for the first time, consistent correlation between the effect on steady-state loss rates and the effect on cell proliferation in the plasmid replication-arrest assay for all three systems. The parDE system had the most pronounced effect both on plasmid stabilization and on plasmid retention after replication arrest. In contrast, ccd and parD both exhibited weaker effects than anticipated from previously published results. Thus, our results indicate that the function and efficiencies of some of the systems should be reconsidered. Our results are consistent with the previously postulated hypothesis that ccd and parDE act by killing plasmid-free segregants, whereas parD seems to act by inhibiting cell division of plasmid-free segregants.
Comparative Activity of Melarsoprol and Arsenic Trioxide in Chronic B-Cell Leukemia Lines (1997)

Inorganic arsenic trioxide (As2O3 ) was recently shown to induce apoptosis in NB4 promyelocytic leukemic cells. We have investigated the effects of the organic arsenical, melarsoprol (a drug used for treatment of trypanosomiasis), upon induction of apoptosis in cell lines representative of chronic B-cell lymphoproliferative disorders. An Epstein-Barr virus (EBV)-transformed B-prolymphocytic cell line (JVM-2), an EBV-transformed B-cell chronic lymphocytic leukemia (B-CLL) cell line (I83CLL), and one non–EBV-transformed B-CLL cell line (WSU-CLL) were used as targets. Dose-response experiments with melarsoprol (10−7 to 10−9 mol/L) were performed over 96 hours. Unexpectedly, we found that melarsoprol caused a dose- and time-dependent inhibition of survival and growth in all three cell lines. In contrast, As2O3 at similar concentrations had no effect on either viability or growth. After 24 hours, all three cell lines treated with melarsoprol (10−7 mol/L) exhibited morphologic characteristics of apoptosis. We also observed prominent concentration-dependent downregulation of bcl-2 mRNA after 24 hours of exposure to melarsoprol in WSU-CLL, I83CLL, and JVM-2 cells. Decrease of bcl-2 protein expression was also observed in all three cell lines, whereas As2O3 had no effect on this parameter. We conclude that melarsoprol may inhibit the growth of lymphoid leukemic cell by promoting programmed cell death. Results of these studies suggest that melarsoprol shows promising therapeutic activity in these diseases, and a study to evaluate clinical effects of this drug has been initiated.
Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance (2016)

In patients with and without statin intolerance, daily treatment with ETC-1002 120 mg and 180 mg alone or with EZE reduced LDL-C more than EZE alone and had a similar tolerability profile (NCT01941836).
Distinct Transcription Profiles of Primary and Secondary Glioblastoma Subgroups (2006)

Glioblastomas are invasive and aggressive tumors of the brain, generally considered to arise from glial cells. A subset of these cancers develops from lower-grade gliomas and can thus be clinically classified as "secondary," whereas some glioblastomas occur with no prior evidence of a lower-grade tumor and can be clinically classified as "primary." Substantial genetic differences between these groups of glioblastomas have been identified previously. We used large-scale expression analyses to identify glioblastoma-associated genes (GAG) that are associated with a more malignant phenotype via comparison with lower-grade astrocytomas. We have further defined gene expression differences that distinguish primary and secondary glioblastomas. GAGs distinct to primary or secondary tumors provided information on the heterogeneous properties and apparently distinct oncogenic mechanisms of these tumors. Secondary GAGs primarily include mitotic cell cycle components, suggesting the loss of function in prominent cell cycle regulators, whereas primary GAGs highlight genes typical of a stromal response, suggesting the importance of extracellular signaling. Immunohistochemical staining of glioblastoma tissue arrays confirmed expression differences. These data highlight that the development of gene pathway-targeted therapies may need to be specifically tailored to each subtype of glioblastoma.
Characteristics of the operon for a putrescine transport system that maps at 19 minutes on the Escherichia coli chromosome. (1993)

The nucleotide sequence of the operon for the putrescine transport system that maps at 19 min on the Escherichia coli chromosome was determined. It contained four open reading frames encoding potF, -G, -H, and -I proteins. The potF protein (M(r) = 38,000) was inferred to be a putrescine-specific binding protein existing in a periplasmic fraction from the results of Western blot analysis of the cell fractions and from measurements of polyamine binding to the protein. The potG protein (M(r) = 45,000) had consensus amino acid sequences for the nucleotide-binding site. The potH (M(r) = 35,000) and potI (M(r) = 31,000) proteins consisted of six putative transmembrane-spanning segments linked by hydrophilic segments of variable length as shown by hydropathy profiles. The spermidine-putrescine transport system, which is mainly involved in spermidine transport, consisted of potA, -B, -C, and -D proteins (Furuchi, T., Kashiwagi, K., Kobayashi, H., and Igarashi, K. (1991) J. Biol. Chem. 266, 20928-20933). The homologies of the corresponding two proteins between those two systems, F and D, G and A, H and B, and I and C, were 35, 42, 37, and 36%, respectively. The initiation point of the transcription of the operon for the putrescine transport system was determined by primer extension and S1 nuclease mapping. Transcription started from the T residue located either 149 or 150 nucleotides upstream from the initiator AUG codon of potF protein mRNA. By making several subclones and a mutant lacking the potF gene, we showed that the expression of all four proteins was necessary for maximal putrescine transport activity. These results indicate that the putrescine transport system can also be defined as a bacterial periplasmic transport system.
The specificity of recognition of a cytotoxic T lymphocyte epitope (1992)

An Epstein-Barr virus (EBV)-specific CD8+ cytotoxic T lymphocyte (CTL) clone (LC13) was shown to recognize the minimal peptide determinant FLRGRAYGL from the EBNA 3 antigen of the BL74 strain of EBV. The equivalent epitope from the B95-8 strain (FLRGRAYGI) is not recognized when endogenously presented and the peptide is 15-fold less active than FLRGRAYGL. A replacement set of peptides was synthesized in which each residue within FLRGRAYGL was sequentially replaced with all other genetically coded amino acids. These peptides were tested for their ability to sensitize target cells to lysis by LC13. Of the 171 single-amino acid replacement peptides only 15 were more active than the peptide FLRGRAYGI. Five peptides had significantly greater activity than FLRGRAYGL and a peptide incorporating the most active of these single-amino acid substitutions (HIRGRAYSL) induced lysis at concentrations approximately 30-fold less than FLRGRAYGL. Simplified theoretical calculations based on this study suggest that CTL LC13 has a specificity for its target epitope of 1 in 4.7 x 10(10). This represents the first complete analysis of the role of single amino acids within a minimum epitope on the specificity of CTL recognition.
Simplified Therapeutic Intervention Scoring System (1996)

The simplified TISS-28 explains 86% of the variation in TISS-76 and can therefore replace the original version in the clinical practice in the ICU. Per shift, a typical nurse is capable of delivering nursing activities equal to 46 TISS-28 points.
Giga-bit DRAM cells with low capacitance and low resistance bit-lines on buried MOSFETs and capacitors by using bonded SOI technology-reversed stacked capacitor (RSTC) cell (2002)

This paper describes a reversed-stacked-capacitor (RSTC) cell for Giga-bit DRAMs, where a storage capacitor and a MOSFET are reversed by using chemical-mechanical-polishing (CMP) and bonded-SOI technology. The virtual flat surface at the bottom of the MOSFET is made into a real surface by polishing. The bit-lines and metal wirings are realized on the flat surface with low-aspect-ratio contact holes throughout the whole chip. This cell structure is suitable for not only Giga-bit DRAMs but also embedded DRAMs. A test memory array is fabricated with a 64 Mbit DRAM design rule. Both capacitance and resistance of bit-lines decreased by a factor of two with this RSTC cell compared to the conventional shielded-bit-line STC cells. The bit-lines are placed far from word-lines and cell-capacitors. The bit-lines are made of low resistivity materials after all the high-temperature processes have been finished.
Synthesis, Structures, and Unique Luminescent Properties of Tridentate C∧C∧N Cyclometalated Complexes of Iridium (2011)

Abstract The first C ∧ C ∧ N cyclometalated complexes of iridium that bear tridentate pyridylbiphenylene ligands are reported herein. These complexes were synthesized in good yields by means of the directed C–C bond activation of biphenylene with the assistance of pyridyl group precoordination. Their photoluminescent performances were also studied and show unique luminescent properties at longer wavelengths in the near‐infrared range than that of previously synthesized C ∧ N ∧ C cyclometalated iridium complexes.
Direct Visualization of Colloidal Rod Assembly by Confocal Microscopy (2005)

The development of model materials and image processing methods to directly visualize and quantify colloidal rod assembly by means of confocal laser scanning microscopy (CLSM) is reported. Monodisperse fluorescent colloidal rods are prepared by the uniaxial extensional deformation of sterically stabilized microspheres at elevated temperatures. The particles are stably dispersed in refractive index matching mixed organic solvents for CLSM. An image processing algorithm is developed to detect rod backbones and extract particle centroids and orientation angles from the CLSM image volumes. By means of these methods we quantify the distribution of rod orientation angles in self-assembled structures of rods formed by sedimentation. We find the observations to be consistent with aspect-ratio-dependent jamming and orientational order/disorder transition in the rod sediments.
Oral immunization with recombinant Mycobacterium bovis BCG simian immunodeficiency virus nef induces local and systemic cytotoxic T-lymphocyte responses in mice (1997)

Recombinant live Mycobacterium bovis BCG vectors (rBCG) induce strong cellular and humoral immune responses against various antigens after either systemic or oral immunization of mice. Cytotoxic T-lymphocyte (CTL) responses may contribute to the control of human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) infections whose portal of entry is the gastrointestinal or genital mucosa. In this study, we immunized BALB/c mice with a recombinant BCG SIV nef and observed its behavior in oropharyngeal and target organ lymphoid tissues. The cellular immune responses, particularly the intestinal intraepithelial and systemic CTL responses, were investigated. The results showed that rBCG SIV nef translocated the oropharyngeal mucosa and intestinal epithelium. It diffused to and persisted in target lymphoid organs. Specific SIV Nef peptide proliferative responses and cytokine production were observed. Strong systemic and mucosal CTL responses were induced. In particular, we demonstrated direct specific anti-Nef CTL in intestinal intraepithelial CD8beta+ T cells. These findings provide evidence that orally administered rBCG SIV nef may contribute to local defenses against viral invasion. Therefore, rBCG SIV nef could be a candidate vaccine to protect against SIV infection and may be used to develop an oral rBCG HIV nef vaccine.
PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro (2009)

These studies suggest a role for CDK4/6 inhibition in some breast cancers and identify criteria for patient selection in clinical studies of PD 0332991
Competitive Activity-Based Protein Profiling Identifies Aza-β-Lactams as a Versatile Chemotype for Serine Hydrolase Inhibition (2012)

Serine hydrolases are one of the largest and most diverse enzyme classes in Nature. Most serine hydrolases lack selective inhibitors, which are valuable probes for assigning functions to these enzymes. We recently discovered a set of aza-β-lactams (ABLs) that act as potent and selective inhibitors of the mammalian serine hydrolase protein-phosphatase methylesterase-1 (PME-1). The ABLs inactivate PME-1 by covalent acylation of the enzyme's serine nucleophile, suggesting that they could offer a general scaffold for serine hydrolase inhibitor discovery. Here, we have tested this hypothesis by screening ABLs more broadly against cell and tissue proteomes by competitive activity-based protein profiling (ABPP), leading to the discovery of lead inhibitors for several serine hydrolases, including the uncharacterized enzyme α,β-hydrolase domain-containing 10 (ABHD10). ABPP-guided medicinal chemistry yielded a compound ABL303 that potently (IC(50) ≈ 30 nM) and selectively inactivated ABHD10 in vitro and in living cells. A comparison of optimized inhibitors for PME-1 and ABHD10 indicates that modest structural changes that alter steric bulk can tailor the ABL to selectively react with distinct, distantly related serine hydrolases. Our findings, taken together, designate the ABL as a versatile reactive group for creating first-in-class serine hydrolase inhibitors.
Gene expression analysis of plant host–pathogen interactions by SuperSAGE (2003)

The type III restriction endonuclease EcoP15I was used in isolating fragments of 26 bp from defined positions of cDNAs. We call this substantially improved variant to the conventional serial analysis of gene expression (SAGE) procedure "SuperSAGE." By applying SuperSAGE to Magnaporthe grisea (blast)-infected rice leaves, gene expression profiles of both the rice host and blast fungus were simultaneously monitored by making use of the fully sequenced genomes of both organisms, revealing that the hydrophobin gene is the most actively transcribed M. grisea gene in blast-infected rice leaves. Moreover, SuperSAGE was applied to study gene expression changes before the so-called hypersensitive response in INF1 elicitor-treated Nicotiana benthamiana, a "nonmodel" organism for which no DNA database is available. Again, SuperSAGE allowed rapid identification of genes up- or down-regulated by the elicitor. Surprisingly, many of the down-regulated genes coded for proteins involved in photosynthesis. SuperSAGE will be especially useful for transcriptome profiling of two or more interacting organisms like hosts and pathogens, and of organisms, for which no DNA database is available.
Stereospecific Preparation of the N-Terminal Amino Acid Moiety of Nikkomycins KX and KZ via a Multiple Enzyme Synthesis (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTStereospecific Preparation of the N-Terminal Amino Acid Moiety of Nikkomycins KX and KZ via a Multiple Enzyme SynthesisDarla P. Henderson, Michael C. Shelton, Ian C. Cotterill, and Eric J. TooneView Author Information Department of Chemistry, Duke University, Durham, North Carolina 27708 Cite this: J. Org. Chem. 1997, 62, 23, 7910–7911Publication Date (Web):November 14, 1997Publication History Received19 August 1997Published online14 November 1997Published inissue 1 November 1997https://pubs.acs.org/doi/10.1021/jo971549shttps://doi.org/10.1021/jo971549srapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views432Altmetric-Citations37LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Aldol reactions,Biopolymers,Monomers,Organic reactions,Peptides and proteins Get e-Alerts
Compact, Efficient Laser Systems Required for Laser Inertial Fusion Energy (2011)

This paper presents our conceptual design for laser drivers used in Laser Inertial Fusion Energy (LIFE) power plants. Although we have used only modest extensions of existing laser technology to ensure near-term feasibility, predicted performance meets or exceeds plant requirements: 2.2 MJ pulse energy produced by 384 beamlines at 16 Hz, with 18% wall-plug efficiency. High reliability and maintainability are achieved by mounting components in compact line-replaceable units that can be removed and replaced rapidly while other beamlines continue to operate, at up to ˜13% above normal energy, to compensate for neighboring beamlines that have failed. Statistical modeling predicts that laser-system availability can be greater than 99% provided that components meet reasonable mean-time-between-failure specifications.
High-affinity monoclonal antibodies to the cardiac glycoside, digoxin. (1982)

Abstract High-affinity anti-digoxin antibodies isolated from antisera are known to reverse the pharmacologic and toxic effects of the widely used cardiac glycoside, digoxin. The technique of somatic cell fusion has the potential of providing an unlimited supply of high-affinity monoclonal antibodies specific for digoxin that are suitable for therapeutic and diagnostic use. We produced seven high-affinity monoclonal anti-digoxin antibodies using this technique. Spleen cells from A/J mice immunized with digoxin coupled to human serum albumin were fused with one of three myeloma cell lines (45.6TG1.7, NS1, or Sp2/0). Antibody production in subcloned cell lines was augmented from micrograms per milliliter in culture media to milligrams per milliliter quantities in ascites. Purification from ascites was accomplished by several means, including affinity chromatography on ouabainamine-Sepharose columns and ion-exchange chromatography on DEAE cellulose. Each hybridoma antibody was analyzed for affinity and specificity by radioimmunoassay (RIA) based on the adsorption of the digoxin hapten to dextran-coated charcoal. All of the monoclonal antibodies demonstrated high affinity constants (2 X 108 to 7 x 109 M–1). Of the seven antibodies analyzed for specificity to structurally related cardiac glycosides, three demonstrated unique sets of inhibition curves. The other four antibodies showed nearly identical patterns in their inhibition profiles. These same four antibodies gave identical patterns on isoelectric focusing. Two hybridomas, Dig 26-10 and Dig 35-20, were shown to be as effective in a clinical RIA for digoxin as sheep anti-digoxin sera and as the anti-digoxin antibody supplied in a commercially available kit. Analysis of the fine specificity for antigen of each of three monoclonal antibodies revealed small differences in the probable orientation of digoxin in the antibody combining site. Characterization of these and other high-affinity monoclonal anti-digoxin antibodies with regard to their variable region amino acid sequences and their antigenic fine specificity for related cardiac glycosides will provide a model system for the study of structure-function relationships between antibody combining site and specific antigenic determinants.
Prediction of chemotherapy response in human leukemia using an in vitro chemotherapy sensitivity test on the leukemic colony-forming cells (1980)

An in vitro test system to quantitatively assess the chemotherapy sensitivity of human acute leukemic colony-forming cells (L-CFU) in relation to normal granulocytic precursor cells (CFU-C) has been developed. After simultaneous exposure of leukemic and normal bone marrow cells to individual drugs in vitro, cells were grown using an improved agar culture method with daily feeding. A sensitivity index (SI) was determined as the ratio of survival fraction of CFU-C to that of L-CFU, L-CFU being more (or less) sensitive than CFU-C if the SI were higher (or lower) than unity. Thirty SI were determined for 6 single drugs actually given in various combinations to a total of 9 patients (8 with acute nonlymphocytic leukemia and 1 with chronic myelomonocytic leukemia). A highly significant correlation was observed between high (or low) SI and achievement of (or failure to achieve) complete remission, with only 6 false correlations (p = 0.0013). Also, the mean of these SI (MSI) for the multiple single drugs given to each patient as components of a combination chemotherapy was used to indicate an overall sensitivity for each trial of the chemotherapy. Among the 10 chemotherapy trials (1 trial each for 8 patients and 2 trials for 1 patient), 4 trials resulting in complete remission had MSI higher than 1.0, and 6 trials not resulting in complete remission had MSI lower than 1.0 (p = 0.0048). This assay system appears useful in predicting the response of patients to chemotherapy and in the selection of the most effective drugs for use in individual patients.
Numerical Vector Green’s Function for S-Parameter Measurement With Waveport Excitation (2017)

We present a numerical vector Green's function that directly links the object material property within the electric field volume integral equation (VIE) to the scattered S-parameters. This Green's function is particularly useful for microwave inverse scattering applications in which S-parameter measurements are used to reconstruct the dielectric properties of unknown objects in an inhomogeneous background where the Green's function does not have an analytic form. Unlike the dyadic Green's function in a standard VIE, which relates the fields in the object domain (vector) to the scattered fields (vector), this vector Green's function kernel relates the object domain fields (vector) to the measured S-parameters (scalar). Also this new vector Green's function uses a waveport source method, which accurately accounts for the measured scattered S-parameters between antenna feeds of arbitrary impedance and modes. A detailed derivation is presented, and simulated and experimental examples are provided to validate this vector Green's function for the prediction of scattered S-parameters.