gebhart/patrepeval huggingface dataset:
Homeotic Transformation of Ovules into Carpel-Like Structures in Arabidopsis (1994)

Zora Modrusan, Leonore Reiser, Kenneth A. Feldmann, Robert L. Fischer, George W. Haughn, Homeotic Transformation of Ovules into Carpel-Like Structures in Arabidopsis, The Plant Cell, Vol. 6, No. 3 (Mar., 1994), pp. 333-349
MuERV-L Is One of the Earliest Transcribed Genes in Mouse One-Cell Embryos1 (2003)

The expression pattern and function of the murine endogenous retrovirus-like (MuERV-L) gene in mouse preimplantation embryos was investigated. MuERV-L was rapidly transcribed from the beginning of S phase (8 h after fertilization) in the first cell cycle. MuERV-L expression was completely repressed when transcription from the zygotic genome was inhibited by alpha-amanitin. These results reveal that MuERV-L is transcribed from the zygotic genome and that it is expressed earlier than any other genes previously reported. In addition, MuERV-L was expressed even when the first round of DNA synthesis was inhibited by aphidicolin, suggesting that its expression is controlled by the zygotic clock. The function of MuERV-L in the development of mouse embryos was also examined using antisense oligonucleotides. The developmental competence of embryos was markedly suppressed after the 4-cell stage when they were treated with antisense oligonucleotides. This result suggests that MuERV-L plays an important role in the development of mouse embryos at the early preimplantation stage.
Natural truncation of RANTES abolishes signaling through the CC chemokine receptors CCR1 and CCR3, impairs its chemotactic potency and generates a CC chemokine inhibitor (1998)

Selective leukocyte trafficking towards sites of inflammation is mediated by chemokines. RANTES is a CC chemokine that attracts lymphocytes, monocytes, dendritic cells, eosinophils, basophils and NK cells. A natural form of human RANTES lacking two N-terminal residues was isolated from stimulated sarcoma cells, fibroblasts, and leukocytes. RANTES(3-68) showed a more than tenfold reduction in chemotactic potency for monocytes and eosinophils. To elucidate the mechanism involved, receptor recognition studies were performed. In cells transfected with the CC chemokine receptor (CCR) 5, the major co-receptor for macrophage-tropic HIV-1 strains, RANTES(3-68) mobilized calcium and desensitized RANTES(1-68)-induced calcium fluxes equally well as RANTES(1-68). However, RANTES(3-68) was ineffective on CCR1 and CCR3 transfectants. The reduced potency of natural RANTES(3-68) by selective loss of receptor-activating characteristics was confirmed with recombinant RANTES(3-68). In chemotaxis assays using monocytic cells, RANTES(3-68) inhibited RANTES(1-68), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta or monocyte chemotactic protein-3 (MCP-3), but not MCP-1- or MCP-2-induced chemotaxis. Thus, a minor post-translational modification has a remarkable impact on the biological activities of RANTES and a pathophysiologically induced change in the relative amounts of intact and truncated RANTES might affect the outcome of inflammation or HIV infection.
Phase I–II study of docetaxel and ifosfamide combination in patients with anthracycline pretreated advanced breast cancer (2003)

Given the established individual activity of docetaxel and ifosfamide in anthracycline pretreated advanced breast cancer, the present phase I-II study aimed to define the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs), and activity of the docetaxel-ifosfamide combination in this setting. Cohorts of three to six patients with histologically confirmed metastatic breast cancer after prior anthracycline-based chemotherapy were treated at successive dose levels (DLs) with escalated doses of docetaxel 70-100 mg x m(-2) over 1 h on day 1 followed by ifosfamide 5-6 g x m(-2) divided over days 1 and 2 (2.5-3.0 g x m(-2) day(-1) over 1 h), and recycled every 21 days. G-CSF was added once dose-limiting neutropenia was encountered at a certain DL and planned to be incorporated prophylactically in subsequent higher DLs. In total, 56 patients with a median age of 54.5 (range, 32-72) years and performance status (WHO) of 1 (range, 0-2) were treated at five DLs as follows: 21 in phase I DLs (DL1: 3, DL2: 6, DL3: 3, DL4: 6, and DL5: 3) and the remaining 35 were treated at DL4 (total of 41 patients at DL4), which was defined as the level for phase II testing. All patients were assessable for toxicity and 53 for response. Dose-limiting toxicity (with the addition of G-CSF after DL2) was reached at DL5 with two out of three initial patients developing febrile neutropenia (FN). Clinical response rates, on an intention-to-treat basis, in phase II were: 53.6% (95% CI, 38.3-68.9%); three complete remissions, 19 partial remissions, seven stable disease, and 12 progressive disease. The median response duration was 7 months (3-24 months), median time to progression 6.5 month (0.1-26 month), and median overall survival 13 months (0.1-33 months). Grade 3/4 toxicities included time to progression neutropenia in 78% of patients-with 63% developing grade 4 neutropenia (<or=7 days) and in 12% of these FN, while no grade 3/4 thrombocytopenia was observed. Other toxicities included peripheral neuropathy grade 2 only in 12%, grade 1/2 reversible CNS toxicity in 17%, no renal toxicity, grade 2 myalgias in 10%, grade 3 diarrhoea in 10%, skin/nail toxicity in 17%, and grade 2 fluid retention in 2% of patients. One patient in the study treated at phase II died as a result of acute liver failure after the first cycle. In conclusion, the present phase I-II study determined the feasibility of the docetaxel-ifosfamide combination, defined the MTD and demonstrated the encouraging activity of the regimen in phase II, thus warranting further randomised phase III comparisons to single-agent docetaxel or combinations of the latter with other active agents.
μ Opioid Receptor Stimulates a Growth Promoting and Pro-Angiogenic Tumor Microenvironment by Transactivating VEGF Receptor-2/Flk-1. (2005)

Abstract Like VEGF, morphine stimulates MAPK/ERK and Akt, leading to the promotion of angiogenesis via NO dependent signaling (Cancer Res62: 4491, 2002). Morphine acts via pertussis toxin (PT)-dependent G-protein coupled receptors (GPCRS), while VEGF acts via receptor tyrosine kinases (RTKs). We showed that PT-dependent GPCRs transactivate VEGF receptor-2/Flk1 via small GTPase RhoA (JBC277: 4679, 2002; JBC278:20738, 2003). Therefore, we hypothesized that morphine via the mu opioid receptor (MOR) transactivates Flk1 and promotes a pro-angiogenic microenvironment. Morphine-induced proliferation of human umbilical vein endothelial cells (HUVEC) was completely abrogated by Y-27632 (100 μM), a highly selective and potent inhibitor of Rho-associated protein kinases, suggesting the activation of Rho signaling by morphine. Addition of 1 μM morphine potentiated VEGF-induced (10 ng/ml) proliferation of HUVEC by 25%. We observed a 30% increase in intracellular calcium release after VEGF stimulation of HUVEC pre-incubated with morphine as compared to HUVEC pre-incubated with PBS, detected by a change in the fluorescence ratio of the Fura-2 AM dye. These findings show that morphine, via MOR and Rho signaling, transactivates Flk1 leading to the stimulation of calcium signaling and endothelial cell proliferation. To functionally corroborate our hypothesis, we used MOR knockout (MOR-KO) mice and injected them with MOR-replete T241 fibrosarcoma cells. T241 fibrosarcoma tumor growth in vivo showed appearance of palpable and measurable tumors 2 days earlier in wild type (wt) as compared to MOR-KO mice. Tumor growth and angiogenesis were decreased by 20–35% in MOR-KO mice as compared to wt littermates during 3 weeks of tumor growth. None of the MOR-KO showed signs of lung metastasis versus 40% wt mice with metastasis. Morphine (1.42 for the first 2 wks and 2.14 mg/Kg/day later, respectively) stimulated 20–35% tumor growth in wt, but not in MOR-KO mice. Western immunoblotting showed a 10-fold increase in the expression of phospho-Flk1 in morphine treated wt tumors as compared to PBS-treated wt mice. Morphine did not stimulate phospho-Flk1 expression in MOR-KO mice. Western analysis of immunoprecipitates obtained with α-MOR antibody showed the expression of Flk1 and phospho-Flk1 in wt, but were not expressed in MOR-KO tumors. Thus, MOR stimulates the transactivation of Flk1 in wt mice but not in MOR-KO. These in vitro and in vivo data using MOR-KO mice and the MOR agonist, morphine, show that MOR stimulates endothelial proliferation, angiogenesis and promotes tumor growth and metastasis directly as well as by transactivating Flk1 phosphorylation. We speculate that MOR is a critical component of the ‘angiogenic switch’, which regulates the pro-angiogenic and growth promoting tumor microenvironment. Thus, MOR provides a novel target for developing anti-angiogenic therapies.
Early mouse endoderm is patterned by soluble factors from adjacent germ layers (2000)

Endoderm that forms the respiratory and digestive tracts is a sheet of approximately 500-1000 cells around the distal cup of an E7.5 mouse embryo. Within 2 days, endoderm folds into a primitive gut tube from which numerous organs will bud. To characterize the signals involved in the developmental specification of this early endoderm, we have employed an in vitro assay using germ layer explants and show that adjacent germ layers provide soluble, temporally specific signals that induce organ-specific gene expression in endoderm. Furthermore, we show that FGF4 expressed in primitive streak-mesoderm can induce the differentiation of endoderm in a concentration-dependent manner. We conclude that the differentiation of gastrulation-stage endoderm is directed by adjacent mesoderm and ectoderm, one of the earliest reported patterning events in formation of the vertebrate gut tube.
Substrate Binding to the α-Ketoglutarate-Dependent Non-Heme Iron Enzyme Clavaminate Synthase 2:  Coupling Mechanism of Oxidative Decarboxylation and Hydroxylation (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSubstrate Binding to the α-Ketoglutarate-Dependent Non-Heme Iron Enzyme Clavaminate Synthase 2: Coupling Mechanism of Oxidative Decarboxylation and HydroxylationJing Zhou, Michele Gunsior, Brian O. Bachmann, Craig A. Townsend, and Edward I. SolomonView Author Information Departments of Chemistry Stanford University, Stanford, California 94305 The Johns Hopkins University, Baltimore, Maryland 21218 Cite this: J. Am. Chem. Soc. 1998, 120, 51, 13539–13540Publication Date (Web):December 9, 1998Publication History Received7 October 1998Published online9 December 1998Published inissue 1 December 1998https://pubs.acs.org/doi/10.1021/ja983534xhttps://doi.org/10.1021/ja983534xrapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views700Altmetric-Citations60LEARN 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:Metal to ligand charge transfer,Organic reactions,Peptides and proteins,Surface interactions,Titration Get e-Alerts
A TECHNIQUE USED ON MOUNDS OF COPTOTERMES LACTEUS TO SCREEN POTENTIAL BAIT SUBSTRATES (1985)

Abstract A simple method designed to rapidly screen potential bait substrates on mounds of Coptotermes lacteus (Froggatt) is described. The apparatus is cheap, readily prepared in the laboratory, and easily installed in the field.
P27kip1 Down-Regulation Is Associated with Trastuzumab Resistance in Breast Cancer Cells (2004)

Trastuzumab (Herceptin) is a recombinant humanized monoclonal antibody directed against HER-2. The objective response rate to trastuzumab monotherapy is 12-34% for a median duration of 9 months, by which point most patients become resistant to treatment. We created two trastuzumab-resistant (TR) pools from the SKBR3 HER-2-overexpressing breast cancer cell line to study the mechanisms by which breast cancer cells escape trastuzumab-mediated growth inhibition. Both pools maintained her-2 gene amplification and protein overexpression. Resistant cells demonstrated a higher S-phase fraction by flow cytometry and a faster doubling time of 24-36 h compared with 72 h for parental cells. The cyclin-dependent kinase inhibitor p27(kip1) was decreased in TR cells, and cyclin-dependent kinase 2 activity was increased. Importantly, exogenous addition of p27(kip1) increased trastuzumab sensitivity. Additionally, resistant cells displayed heightened sensitivity to the proteasome inhibitor MG132, which induced p27(kip1) expression. Thus, we propose that trastuzumab resistance may be associated with decreased p27(kip1) levels and may be susceptible to treatments that induce p27(kip1) expression.
Phage display : a practical approach (2004)

1. Introduction to phage biology and phage display 2. Constructing phage display libraries by oligonucleotide-directed mutagenesis 3. In vitro DNA recombination 4. Phage selection strategies for improved affinity and specificity of proteins and peptides 5. Rapid screening of phage displayed protein binding affinities by phage ELISA 6. Identification of novel ligands for receptors using recombinant peptide libraries 7. Substrate phage display 8. Protease-based selection of stably folded proteins and protein domains from phage display libraries 9. Phage display of zinc fingers and other nucleic acid-binding motifs 10. In vivo and ex vivo selections using phage-displayed libraries 11. Screening phage libraries with sera 12. Interaction cloning using cDNA libraries displayed on phage 13. Phage antibody libraries 14. Affinity maturation of phage antibodies
Topical treatment of psoriatic skin with methotrexate cream: a clinical, pharmacokinetic, and histological study (1986)

Five patients were treated with either 0.25% methotrexate cream or placebo in a double blind trial. The evaluation showed no clinical or histological effect although the drug was absorbed from the skin. Methotrexate (MTX) accumulated in locally treated psoriasis plaques as well as in untreated plaques. The psoriatic skin concentrations were increased by a factor of 119 and 4, respectively. This observation is discussed in relation to the possible role of action of methotrexate in psoriasis. We suggest that methotrexate inhibits the chemotaxis of neutrophil leukocytes systemically and not primarily in the skin, thereby preventing development of the early stages in the psoriatic lesions.
TOR Mutations Confer Rapamycin Resistance by Preventing Interaction with FKBP12-Rapamycin (1995)

The antifungal, immunosuppressive compound rapamycin arrests the cell cycle in G1 in both yeast cells and T-lymphocytes. Previous genetic studies in yeast identified mutations in three genes, FPR1 (FKBP12), TOR1, and TOR2, which confer rapamycin resistance, and genetic findings implicated the TOR proteins as direct targets of FKBP12-rapamycin. Consistent with this model, we find that modulating TOR1 and TOR2 expression alters rapamycin sensitivity. We describe several TOR2 mutations that confer rapamycin resistance. These mutations prevent FKBP12-rapamycin binding to TOR2, as assayed with the two-hybrid system. We find that TOR1 and the mammalian TOR homologue (mTOR) also bind FKBP12-rapamycin, and mutations corresponding to those in TOR2 similarly block FKBP12-rapamycin binding. We demonstrate that FKBP12 prolyl isomerase activity is not required for FKBP12-rapamycin binding to TOR and that a composite protein-drug surface contacts the TOR proteins. These studies confirm that the TOR proteins are direct targets of FKBP12-rapamycin, reveal that drug-resistant mutations prevent this association, and define structural features of these complexes.
The bacterial phosphotransferase system: new frontiers 30 years later (1994)

In 1964, Kundig, Ghosh and Roseman reported the discovery of the phosphoenolpyruvate:sugar phosphotransferase system (PTS). Thirty years later, we find that the PTS functions not only as a sugar-phosphorylating system, but also as a complex protein kinase system that regulates a wide variety of metabolic processes and controls the expression of numerous genes. As a result of recent operon- and genome-sequencing projects, novel PTS protein-encoding genes have been discovered, most of which have yet to be functionally defined. Some of them appear to be involved in cellular processes distinct from those recognized previously. Fundamental aspects of past and current PTS research are briefly reviewed, and recent advances are integrated into conceptual pictures that provide guides for future research.
LOCAL UTERINE MECHANISMS AFFECTING LUTEAL FUNCTION IN THE SHEEP (1966)

Summary. The ovary not containing the corpus luteum was removed from each of fifty-two ewes on Day 8 of the cycle. These animals were then allocated to one of the following groups. Group 1 : (control) received no further treatment. Group 2: the contralateral uterine horn, i.e. located on the side opposite to the corpus luteum, was removed. Group 3 : the ipsilateral uterine horn, i.e. located on the same side as the corpus luteum, was removed. Neither unilateral ovariectomy alone (Group 1) nor the removal of the contralateral horn (Group 2) affected the length of the post-operative oestrous cycles. In contrast, extirpation of the ipsilateral uterine horn (Group 3) resulted in a significant extension of the oestrous cycle and thus of the life-span of the corpus luteum. The results suggest that the ovaries of the cyclical sheep are probably affected by the uterus in a local manner.
Reductive Aminations of Carbonyl Compounds with Borohydride and Borane Reducing Agents (2002)

Abstract Reductive amination is an important tool for synthetic organic chemists in the construction of carbon‐nitrogen bonds. This reaction, also termed reductive alkylation, involves condensation of an aldehyde or ketone with an amine in the presence of a reducing agent. A wide variety of substrates can be used including aliphatic and aromatic aldehydes and ketones, and even benzophenones. A range of amines from ammonia to aromatic amines, including those with electron‐withdrawing substituents, can be employed. For particularly sluggish reactions, such as those involving weakly electrophilic carbonyl groups, poorly nucleophilic amines, or sterically congested reactive centers, additives such as molecular sieves or Lewis acids are often useful. This chapter focuses on those conditions in which the carbonyl component, amine, and reducing reagent react in the same vessel. This review is restricted to reductive aminations using borohydride and borane reducing agents. This chapter concentrates on reductive amination chemistry mediated by borohydride and other boron‐containing reducing agents from 1971, the year when sodium cyanoborohydride was introduced, through the middle of 1999. In addition to reductive aminations of aldehyde and ketone substrates, reactions of related structures including acetals, aminals, ketals, carboxylic acids, nitriles, and dicarbonyls that form a nitrogen‐containing ring are reviewed. Intramolecular processes in which the substrate contains both the carbonyl and amine moieties are described. The intramolecular variant is a useful method for preparing cyclic amines. All of the various boron‐containing hydride sources in reductive aminations, including labeled metal hydrides, are reviewed. Instances of reductive aminations that failed are described. Applications of this method to a solid support in parallel synthesis in combinatorial chemistry as well as reductive aminations that proceed in tandem with a second reaction such as reductive lactamizations are discussed.
Enzymatic Biofuel Cells for Implantable and Microscale Devices (2004)

ADVERTISEMENT RETURN TO ISSUEPREVArticleEnzymatic Biofuel Cells for Implantable and Microscale DevicesScott Calabrese Barton, Josh Gallaway, and Plamen AtanassovView Author Information Department of Chemical Engineering, Columbia University, New York, New York 10027, and Department of Chemical and Nuclear Engineering, University of New Mexico, Albuquerque, New Mexico 87131 Cite this: Chem. Rev. 2004, 104, 10, 4867–4886Publication Date (Web):September 21, 2004Publication History Received26 July 2004Published online21 September 2004Published inissue 1 October 2004https://pubs.acs.org/doi/10.1021/cr020719khttps://doi.org/10.1021/cr020719kresearch-articleACS PublicationsCopyright © 2004 American Chemical SocietyRequest reuse permissionsArticle Views11434Altmetric-Citations1257LEARN 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 SUBJECTS:Biofuels,Electrodes,Fuel cells,Peptides and proteins,Redox reactions Get e-Alerts